HISTOLOGY REVIEW

<body topmargin=0 leftmargin=0 marginheight=0 marginwidth=0> <table cellpadding=0 cellspacing=0 border=0><tr> <td valign="top" colspan=2 height=22 BGCOLOR="#FFFFFF" TEXT="#080000" bgproperties="fixed" background="041000d2egerdp.gif"> <div> </div> </td> </tr><tr> <td valign="top" width=145 BGCOLOR="#333399" TEXT="#080000" background="040a2c00erkjzj.gif"> <div> <IMG SRC="15b9f890.gif" border=0 width="159" height="137" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="126776a0.gif" border=0 width="119" height="106" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="15ca1f20.gif" border=0 width="161" height="242" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="12965800.gif" border=0 width="101" height="128" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="12768750.gif" border=0 width="104" height="117" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </td> <td valign="top" height=458 BGCOLOR="#FFFFFF" TEXT="#080000"> <div> <FONT SIZE="5" COLOR="#336600" FACE="Times New Roman" ><I>NEUROPATHOLOGY</I></FONT><FONT SIZE="1" COLOR="#663399" FACE="Times New Roman" >    </FONT> |    <B> </B><FONT SIZE="2" COLOR="#0000BF" FACE="Times New Roman" ><A HREF="index.htm" TARGET="_top" TITLE="NEUROPATHOLOGY"><U><B>home</B></U></A></FONT></div> <div> <B>HISTOLOGY REVIEW</B><B>   |   </B><A HREF="id19.htm" TARGET="_top" TITLE="PHYSIOLOGY REVIEW"><U>PHYSIOLOGY REVIEW</U></A><B>   |   </B><A HREF="id20.htm" TARGET="_top" TITLE="PATHOLOGY part1"><U>PATHOLOGY part1</U></A><B>   |   </B><A HREF="id22.htm" TARGET="_top" TITLE="pathology part2"><U>pathology part2</U></A><B>   |   </B><A HREF="id26.htm" TARGET="_top" TITLE="PATHOLOGY3"><U>PATHOLOGY3</U></A><B>   |   </B><A HREF="id27.htm" TARGET="_top" TITLE="PATHOLOGY 4"><U>PATHOLOGY 4</U></A><B>   |   </B><A HREF="id21.htm" TARGET="_top" TITLE="PICTURES"><U>PICTURES</U></A><B>   |   </B><A HREF="id31.htm" TARGET="_top" TITLE="tumor gn"><U>tumor gn</U></A><B>   |   </B><A HREF="id30.htm" TARGET="_top" TITLE="multiple sclerosis"><U>multiple sclerosis</U></A><B>   |   </B><A HREF="id24.htm" TARGET="_top" TITLE="quiz"><U>quiz</U></A><B>   |   </B><A HREF="id23.htm" TARGET="_top" TITLE="quizanswer"><U>quizanswer</U></A><B>   |   </B><A HREF="id17.htm" TARGET="_top" TITLE="Contact Me and links"><U>Contact Me and links</U></A><B>   |   </B><A HREF="id29.htm" TARGET="_top" TITLE="info and news"><U>info and news</U></A></div> <div> <IMG SRC="04207040.gif" border=0 width="263" height="4" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <div> <B>HISTOLOGY REVIEW</B></div> <div> see also the neuroanatomy site[ link from my <A HREF="http://pathologylectures.homestead.com" TARGET="_top" TITLE="http://pathologylectures.homestead.com"><U>pathologylectures</U></A> site]</div> <bR> <DIV ALIGN="LEFT"></DIV> <div> <IMG SRC="18ab11e0.gif" border=0 width="433" height="286" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <bR> <bR> <div> <B>Landmarks of the </B><FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><B><U>hindbrain:</U></B></FONT><B> cranial nerves and cerebellum</B></div> <div> -the <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>cerebellum</U></FONT>, a "little brain" that works together with cortex to produce movement and process sensory information</div> <div> -various <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>fiber tracts</U></FONT> ascending or descending to various levels of the neuraxis.</div> <div> -groups of interneurons receiving sensory information and</div> <div> -other groups that generate certain motor programs such as breathing.</div> <div>  <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><B><U>The midbrain</U></B></FONT><B>, </B><FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><B><U>tectum and tegmentum:</U></B></FONT></div> <div> -The midbrain consists of a roof (tectum) and a floor (tegmentum).</div> <div> -The tectum has two major sensory processing nuclei that look, from the outside, like little hills (<I>colliculi</I>). The superior (anterior) colliculus processes visual information and the inferior (posterior) colliculus processes auditory inform ation.</div> <div> -The tegmentum consists of various fiber tracts and some interneurons involved in generating motor patterns. </div> <bR> <bR> <div> <B><U>The forebrain</U></B></div> <div> -the hypothalamus is located in the ventral diencephalon; many of its <I>nuclei</I> control the pituitary (aka "master gland").</div> <div> <FONT SIZE="3" COLOR="#000000" FACE="Arial" >-The </FONT><U>thalamus</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > is located in the dorsal diencephalon; cells in the thalamus project to cortex and receive porjections from cortex; the </FONT><I><U>lateral</U></I><U> geniculate</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > nucleus provides visual information to cortex and the medial geniculate nucleus provides audito ry information to cortex.</FONT></div> <div> -The <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>basal ganglia </U></FONT>have reciprocal connections with thalamus and motor cortex and play important roles in motor control (Parkinson's and Huntington's).</div> <div> -The <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>cortex</U></FONT> is an elaborate, crumpled, thick sheet of cells that has reciprocal connections with thalamus and brain stem. The cortex plays an essential role in perceiving, thinking and the planning and execution of movements.</div> <bR> <div> <B>The Cerebral Cortex</B></div> <div> -In humans and primates, the <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>cephalic flexture</U></FONT> at the level of the forebrain and we distinguish a new plane of section, perpendicular still to the neuraxis, the <I>coronal</I> plane.</div> <div> -The cortex is divided into a number of functionally and <I>cytoarchitectonically</I> distinct regions.</div> <div> -The main subdivisions are: frontal, parietal, occipital and temporal.</div> <div> <FONT SIZE="3" COLOR="#000000" FACE="Arial" >-The crumpled surface of the cortex can be viewed as hills </FONT><U>(</U><I><U>gyri</U></I><U>) and valleys (</U><I><U>sulci</U></I><U>)</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" >. Several large sulci divide up the main subdivisions.</FONT></div> <div> -The spatial representation of information is maintained in the cortex as "maps"; maps representing parts of the body are "somatotopic," a map of the body is called an <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>homunculus</U></FONT>. Visual maps are "visuotopic" etc. <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>Motor maps</U></FONT> are also somatotopic. A given region of cortex can contain multiple maps.</div> <div> -In general, the larger a region of cortex devoted to a particular job (body part, region of visual space, etc.) the smaller the receptive fields of neurons in that region.</div> <bR> <div> <IMG SRC="165a9450.jpg" border=0 width="425" height="325" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The brain consists of neurons and glial cells.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Glial cells are astrocytes, oligodendroglia, ependymal cells, and microglia. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">With H&E stains, the brain resembles mesenchymal tissues in which cells are set in an extracellular matrix.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The fibrillary "matrix" of the cerebral gray matter, <B><U>the </U></B><B><U>neuropil</U></B><B>,</B> is formed by the cellular extensions (processes) of the neurons and glial cells. </div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These processes fit together tightly, leaving a minimal extracellular space. </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">There is no extracellular matrix in the CNS.</B><FONT SIZE="3" COLOR="#FF0000" FACE="Arial" ><B> </B></FONT></div> <bR> <bR> <div> <B><U>NEURONS</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><U> </U></FONT></div> <div> <IMG SRC="1736d890.jpg" border=0 width="621" height="393" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <div> <B>There are three kinds of neurons: </B></div> <div> <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><B><U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">primary sensory neurons</U></B></FONT><B>, </B></div> <div> <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><B><U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">motor neurons</U></B></FONT><B>and </B></div> <div> <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><B><U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">interneurons</U></B></FONT><B>. </B></div> <bR> <div> <B>The central nervous system (CNS) is almost entirely interneurons.</B> </div> <div> 1. <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>Primary sensor neurons</U></FONT> convey information into the central nervous system </div> <div> - cell bodies lie OUTSIDE the brain and spinal cord. </div> <div> 2. <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>Motor neurons</U></FONT> send axons out of the brain orspinal cord to <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>synapse on muscles</U></FONT>; </div> <div> -cell bodies INSIDE the central nervous system </div> <div> 3. <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>Interneurons</U></FONT>: both the cell body and all processes are inside the CNS </div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Each neuron has a cell body (the perikaryon), an axon and dendrites. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The dendritic tree is the receptive part of the neuron. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The axon conveys the signal to its target.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The cell body contains the nucleus and most organelles that perform the synthetic and catabolic activities that keep the neuron and all its parts alive and functioning.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Neurons come in all sizes.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Motor neurons, which are the largest cells in the CNS, have a cell body measuring up to 135 microns.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Granular neurons of the cerebellum, which are the smallest, measure 4 microns</div> <div> <IMG SRC="0a2f4020.gif" border=0 width="500" height="258" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><FONT SIZE="3" COLOR="#000000" FACE="Arial" >2 Spinal motor neuron (left) and Purkinje and granular neurons of the cerebellar cortex (right).</FONT></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Large neurons have abundant rough endoplasmic reticulum (RER) which forms aggregates, <B><U>the Nissl </U></B>granules.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> These are easy to see with cellular stains such as the Nissl stain and H&E.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> If the axon is transsected, the<B><U> RER disaggregates</U></B>.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The neuronal body balloons. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The cytoplasm becomes smooth and the nucleus is displaced toward the periphery of the cell.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> This appearance, which is called <B>central chromatolysis</B>, is a reversible change that develops during repair of a neuron that has been disconnected from its target.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Neurons contain numerous mitochondria that are needed for aerobic energy production. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Deficiencies of mitochondrial enzymes affect primarily the brain and muscle.</div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In the brain, mitochondrial disorders cause neuron loss and present as encephalopathy, myoclonus, strokes, and other clinical disorders.</U></B> </div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Hypoxia, ischemia and hypoglycemia cause irreversible neuronal injury</U></B>. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Injured neurons shrink, become eosinophilic due to condensation of mitochondria, and their nuclei become pyknotic. Such neurons are referred to as<U> </U><B><U>anoxic neurons</U></B></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Neurons contain numerous lysosomes used for life-long recycling of biomolecules and organelles. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Deficiency of lysosomal enzymes causes unrecycled substrates of these enzymes to accumulate in lysosomes.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Abnormal lysosomes gradually fill the cell body and processes, leading to destruction of neurons.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> There are many genetically transmitted lysosomal enzyme deficiencies (<B>neuronal storage diseases</B>). </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The best known example is Tay-Sachs disease</B></div> <bR> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Neurofilament proteins are chemically distinct from intermediate filaments of other cells.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Neurotubules are polymers of <FONT SIZE="3" COLOR="#FF0000" FACE="Verdana" ><B><U>alpha and beta tubulin</U></B></FONT>.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Cross bridges made up of <B><U>tau protein and microtubule associated proteins (MAPs)</U></B>, link neurotubules to one another and anchor them to other cellular structures. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The neurotubules and neurofilaments form the cytoskeleton of nerve cells. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They impart shape and structural stability and guide axoplasmic flow. </div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f0ff003300.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In </U></B><B><U>Alzheimer disease</U></B><B><U>, abnormal filaments (paired helical filaments) appear in the perikaryon, forming neurofibrillary tangles (NFTs).</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The most important parts of the neuronal membrane are the synapses</div> <div> <IMG SRC="0a602ae0.gif" border=0 width="514" height="430" ALIGN="LEFT" HSPACE="0" VSPACE="0"><FONT SIZE="3" COLOR="#000000" FACE="Arial" >Synapse. Synaptic vesicles in axon terminals</FONT></div> <bR> <bR> <bR> <bR> <bR> <bR> <bR> <bR> <bR> <bR> <bR> <bR> <bR> <bR> <bR> <bR> <bR> <bR> <div> <IMG SRC="13968c70.gif" border=0 width="360" height="455" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="13a67670.gif" border=0 width="359" height="359" ALIGN="BOTTOM" HSPACE="0" VSPACE="0">presynaptic axones<IMG SRC="13b65650.gif" border=0 width="357" height="357" ALIGN="BOTTOM" HSPACE="0" VSPACE="0">synaptic vesicles</div> <bR> <div> <IMG SRC="1449fc60.jpg" border=0 width="159" height="198" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="14351650.jpg" border=0 width="81" height="101" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <div> <IMG SRC="1472a120.jpg" border=0 width="298" height="274" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="14868330.jpg" border=0 width="360" height="307" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="149602c0.jpg" border=0 width="352" height="300" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A presynaptic element, an <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>axon</U></FONT>, and a postsynaptic element, for example a <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>dendritic spine</U></FONT>, are in close apposition at the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >synapse</FONT> but not in direct contact.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The pre- and postsynaptic membranes are separated by a gap, the <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>synaptic cleft</U></FONT>.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Chemical transmitters bridge this gap by diffusing from release sites on the presynaptic side to receptors on the postsynaptic side. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A variety of ultrastructural specializations occur at the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >synapse</FONT> enabling unambiguous identification of the pre- and postsynaptic partners. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Within the presynaptic axonal bouton, clouds of <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>synaptic vesicles</U></FONT> are prominent; <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>mitochondria</U></FONT> may be present, as well as tubules of <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>endoplasmic reticulum</U></FONT>. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A characteristic feature of the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >synapse</FONT> is the accumulation of opaque material on the cytoplasmic face of the postsynaptic membrane. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This material is refered to as the <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>postsynaptic density</U></FONT>. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The density represents the aggregation of neurotransmitter receptors and signaling proteins essential for chemical synaptic transmission</div> <bR> <div> <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>Gray</U></FONT> classified two types of <FONT SIZE="3" COLOR="#800000" FACE="Arial" >synapse</FONT>s within the brain based on the ultrastructural characteristics of the presynaptic (vesicle-bearing) and postsynaptic partners (length of apposed membrane, membrane thickenings and synaptic cleft): </div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Type 1</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Type 2</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> These two categories were further distinguished by their locations: Type 1 <FONT SIZE="3" COLOR="#800000" FACE="Arial" >synapse</FONT>s were found on dendritic spines and dendrite shafts, whereas Type 2 <FONT SIZE="3" COLOR="#800000" FACE="Arial" >synapse</FONT>s occurred primarily on dendrite shafts and neuronal cell bodies. Virtually synonymous with Gray's nomenclature are the terms: </div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Asymmetric </U><FONT SIZE="3" COLOR="#800000" FACE="Arial" ><U>Synapse</U></FONT><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Symmetric </U><FONT SIZE="3" COLOR="#800000" FACE="Arial" ><U>Synapse</U></FONT><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> described by <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>Colonnier</U></FONT>. Colonnier extended the observations of Gray using aldehyde-fixed brain. In aldehyde-fixed tissue, <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>asymmetric </U></FONT><FONT SIZE="3" COLOR="#800000" FACE="Arial" ><U>synapses</U></FONT> include axons that contain predominantly round or spherical vesicles and form <FONT SIZE="3" COLOR="#800000" FACE="Arial" >synapse</FONT>s that are distinguished by a thickened, postsynaptic density. In contrast, <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>symmetric </U></FONT><FONT SIZE="3" COLOR="#800000" FACE="Arial" ><U>synapses</U></FONT> involve axons that contain clusters of vesicles that are predominantly flattened or elongate in their appearance.</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The pre-and postsynaptic membranes are more parallel than the surrounding nonsynaptic membrane, and the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >synapse</FONT> does not contain a prominent postsynaptic density.  to view Colonier's description of asymmetric and symmetric <FONT SIZE="3" COLOR="#800000" FACE="Arial" >synapse</FONT>s. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The sterotypical and most abundant <FONT SIZE="3" COLOR="#800000" FACE="Arial" >synapse</FONT> in the central nervous system is the asymmetric <FONT SIZE="3" COLOR="#800000" FACE="Arial" >synapse</FONT> occurring between an axon and a <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>dendritic spine</U></FONT>.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Other synaptic relationships exist and involve different parts of the neuron. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">For instance, axo-axonic, somato-axonic, somato-dendritic, dendro-axonic, and <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>dendro-dendritic</U></FONT> <FONT SIZE="3" COLOR="#800000" FACE="Arial" >synapse</FONT>s can occur and provide alternate mechanisms for functional communication between neurons. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Structural and functional classifications of axons, dendrites and their <FONT SIZE="3" COLOR="#800000" FACE="Arial" >synapse</FONT>s are still emerging.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The use of electrophysiology, laser scanning, and serial electron microscopy, together with 3D computer-aided reconstruction, facilitate the study of neurons and the intricacies of their <FONT SIZE="3" COLOR="#800000" FACE="Arial" >synapse</FONT>s within the brain. </div> <bR> <bR> <div> <FONT SIZE="2" COLOR="#000000" FACE="Arial" ><IMG SRC="13cd07d0.gif" border=0 width="464" height="381" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></FONT>Dendro-Dendritic <FONT SIZE="3" COLOR="#800000" FACE="Arial" >Synapse</FONT>s From Cat Thalamus</div> <div> Two Dendrites (D1, D2) make reciprocal <FONT SIZE="3" COLOR="#800000" FACE="Arial" >synapse</FONT>s in the lateral geniculate nucleus. Arrows point to synaptic vesicles and presumed polarity of chemical transmission. Also, an axon (A) makes an asymmetric <FONT SIZE="3" COLOR="#800000" FACE="Arial" >synapse</FONT> on D2. (x 33 000) </div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Most synapses develop on thorn like processes of dendrites, the dendritic spines.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Each synapse consists of the presynaptic process (axon terminal), the synaptic cleft and the postsynaptic process (part of a dendrite). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The axon terminal contains neurotransmitters packaged in synaptic vesicles. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The membrane of these vesicles contains special proteins, including <FONT SIZE="3" COLOR="#3333FF" FACE="Verdana" ><B><U>synaptophysin and synapsins.</U></B></FONT> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Upon excitation, the synaptic vesicles fuse with the synaptic membrane and discharge their contents into the synaptic cleft.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Contact of neurotransmitters with receptors on the postsynaptic membrane elicits cellular reactions that transmit the message to the postsynaptic neuron.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The Hematoxylin and Eosin (H&E) stain is adequate for routine study of cellular details of neurons and glial cells, but does not stain the neuronal processes. </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Axons and dendrites are demonstrated best with silver stains in which ammoniacal silver is deposited on cytoskeletal components and then reduced to black metallic silver.</B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The most commonly used silver stain is the </B><B>Bielschowsky stain</B><B>,</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> </B></FONT><B>which shows normal axons and dendrites and reveals also the lesions of Alzheimer disease. </B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Specific chemical components of nerve cells such as cytoskeletal proteins and synaptophysin, can be demonstrated by immunohistochemical methods.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The generic term "degeneration" in reference to the cortex or other neuronal systems (e.g. striatonigral degeneration, cerebellar degeneration) means gradual neuron atrophy and eventual loss. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Such a process characterizes most "neurodegenerative" diseases.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In some of these diseases, such as <B>Alzheimer disease</B> and <B>Parkinson disease</B>, there are also specific histopathologic changes.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In others, there is only neuronal loss, brain atrophy and gliosis.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The term "neuronal plasticity" (meaning originally the ability to mold, change shape) refers to change or adaptation of neuronal function dependent on activity.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> A clinical example of plasticity is resumption of a function, e.g. speaking or control of swallowing, by another group of neurons when the neurons that originally performed this function are lost due to a stroke. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The best known laboratory example of plasticity is long term potentiation.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The neuronal structure, especially the density of dendritic spines, changes as a result of neuronal activity.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Neuronal plasticity is the basis of learning.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <B><U>Neuropil of Stratum Radiatum</U></B></div> <bR> <div> The stratum radiatum located next to the layer of pyramidal cells in <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>hippocampal area CA1</U></FONT> is a <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>cell body-poor</U></FONT>, finely textured zone striated by <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>dendritic shafts</U></FONT> running in parallel from apices of pyramidal cells </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"><IMG SRC="13d61a70.jpg" border=0 width="609" height="423" ALIGN="BOTTOM" HSPACE="0" VSPACE="0">This unique felty substance, believed to be one of the most highly organized in the Universe, is called <I>neuropil</I>.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> It represents a complicated spatial network comprising interconnected neuronal processes intermingled with irregularly shaped processes of astrocytic glia. Here in the hippocampus most <FONT SIZE="3" COLOR="#800000" FACE="Arial" >synapse</FONT>s occur in neuropil. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They are located mainly on <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>dendritic spines</U></FONT>. Synaptic neuropil is the basic constituent of the gray matter of the brain and spinal cord. </div> <div> <IMG SRC="13e805d0.gif" border=0 width="640" height="349" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <bR> <div> <B><U>Smooth Endoplasmic Reticulum in Dendrites and their Spines</U></B><B><U> </U></B></div> <bR> <div> <B>Smooth endoplasmic reticulum (SER) is important for regulating calcium which has been shown to be present at high levels in activated dendritic spines. The dimensions and organization of the SER in rat hippocampal spines and dendrites were measured through serial electron microscopy and three-dimensional analysis. This figure illustrates the three-dimensional reconstruction of the SER (</B><B>purple</B><B>) in a rat hippocampal CA1 dendritic segment. In both figures, the membrane of the dendrite is not visible, although in the left figure the membrane of the attached spine is present. The left side shows that the SER in the dendrite is contiguous with the SER entering the thin neck of a large dendritic spine (</B><B>grey</B><B>). The SER in the head of the spine (seen in the right figure where the spine membrane is invisible) is thought to provide </B><FONT SIZE="2" COLOR="#800000" FACE="Arial" ><B>synapse</B></FONT><B>-specific regulation of calcium and other molecules. This particular dendritic spine has a highly irregular synaptic area (</B><B>red</B><B>).</B><B> </B></div> <div> <B>Reference: Spacek, J. and Harris, K.M. (1997) J. Neuroscience, </B><B>17</B><B>(1):190-203</B></div> <bR> <div> <B><IMG SRC="13f94220.jpg" border=0 width="660" height="290" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></B></div> <bR> <div> <B><U>Morphology of Dendrites</U></B></div> <bR> <bR> <div> <IMG SRC="14ad4cf0.gif" border=0 width="468" height="207" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <div> A neuron typically has many dendrites and one axon. The dendrites branch and terminate in the vicinity of the cell body. In contrast, axons can extend to distant targets, more than a meter away in some instances. </div> <div> Dendrites are rarely more than about a millimeter long and often much shorter</div> <bR> <div> Neurons communicate through specialized junctions called <FONT SIZE="3" COLOR="#800000" FACE="Arial" ><I><U>synapses</U></I></FONT>. Axons typically make <FONT SIZE="3" COLOR="#800000" FACE="Arial" >synapse</FONT>s with other neurons through specialized enlargements near their terminals. These <FONT SIZE="3" COLOR="#800000" FACE="Arial" >synapse</FONT>s can occur on the cell bodies or the axons of other neurons, but most frequently they occur on dendrites. Thus, the dendrites of a neuron provide a surface for receiving synaptic inputs from other neurons. </div> <div> The arbor formed by the dendrites of a neuron often has a characteristic shape as determined by the spatial domains into which the dendrites ramify</div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="819" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="191"><div> <B>Pattern </B></div> </tD> <tD VALIGN=CENTER WIDTH="212"><div> <B>Characteristics </B></div> </tD> <tD VALIGN=CENTER WIDTH="396"><div> <B>Examples </B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 91 ><NOBR><div> <B>Adendritic</B></div> <div> <IMG SRC="14b9c450.gif" border=0 width="156" height="69" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </NOBR></tD> <tD VALIGN=CENTER><NOBR><div> Cell body lacks dendrites </div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="396"><div> Dorsal root ganglion cells</div> <div> Sympathetic ganglion cells </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 68 ><NOBR><div> <B>Spindle radiation</B></div> <div> <IMG SRC="14c982a0.gif" border=0 width="152" height="42" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="212"><div> Two dendrites emerge from opposite poles of the cell body and have few branches </div> </tD> <tD VALIGN=CENTER WIDTH="396"><div> Lugaro cells</div> <div> Bipolar cells of cortex </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 153 WIDTH="191"><div> <B>Spherical radiation:</B> Stellate</div> <div> <IMG SRC="14d9c700.gif" border=0 width="156" height="112" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </tD> <tD VALIGN=CENTER WIDTH="212"><div> Dendrites radiate in all directions from cell body </div> </tD> <tD VALIGN=CENTER WIDTH="396"><div> Spinal neurons</div> <div> Cerebellar granule cells</div> <div> Neurons of subcortical nuclei (e.g. inferior olive, pons, thalamus, striatum) </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 153 WIDTH="191"><div> <B>Spherical radiation:</B> Partial</div> <div> <IMG SRC="14e9c700.gif" border=0 width="156" height="112" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </tD> <tD VALIGN=CENTER WIDTH="212"><div> Dendrites radiate from cell body in directions restricted to a part of a sphere </div> </tD> <tD VALIGN=CENTER WIDTH="396"><div> Neurons at edges of "closed" nuclei (e.g. Clarke's column, inferior olive, vestibular nuclei) </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 74 ><NOBR><div> <B>Laminar radiation:</B> Planar</div> <div> <IMG SRC="14f9c340.gif" border=0 width="156" height="52" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="212"><div> Dendrites radiate from cell body in all directions within a thin domain </div> </tD> <tD VALIGN=CENTER WIDTH="396"><div> Retinal horizontal cells </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 77 ><NOBR><div> <B>Laminar radiation:</B> Offset</div> <div> <IMG SRC="1509c370.gif" border=0 width="156" height="55" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="212"><div> Plane of radial dendrites offset from cell body by one or more stems </div> </tD> <tD VALIGN=CENTER WIDTH="396"><div> Retinal ganglion cells </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 86 ><NOBR><div> <B>Laminar radiation:</B> Multi</div> <div> <IMG SRC="1519c400.gif" border=0 width="156" height="64" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="212"><div> Cell has multiple layers of radial dendrites </div> </tD> <tD VALIGN=CENTER WIDTH="396"><div> Retinal amacrine cells </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 98 ><NOBR><div> <B>Cylindrical radiation</B></div> <div> <IMG SRC="1529c4c0.gif" border=0 width="156" height="76" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="212"><div> Dendrites ramify from a central soma or dendrite in a thick cylindrical (disk-shaped) domain </div> </tD> <tD VALIGN=CENTER WIDTH="396"><div> Pallidal neurons</div> <div> Reticular neurons </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 102 ><NOBR><div> <B>Conical radiation</B></div> <div> <IMG SRC="15390500.gif" border=0 width="144" height="80" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="212"><div> Dendrites radiate from cell body or apical stem within a cone or paraboloid </div> </tD> <tD VALIGN=CENTER><NOBR><div> Granule cells of dentate gyrus and olfactory bulb</div> <div> Primary dendrites of mitral cells of olfactory bulb</div> <div> Semilunar cells of piriform cortex </div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 162 ><NOBR><div> <B>Biconical radiation</B></div> <div> <IMG SRC="1549c8c0.gif" border=0 width="156" height="140" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="212"><div> Dendrites radiate in opposite directions from the cell body </div> </tD> <tD VALIGN=CENTER WIDTH="396"><div> Bitufted, double bouquet, and pyramidal cells of cerebral cortex</div> <div> Vertical cells of superior colliculus </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 162 ><NOBR><div> <B>Fan radiation</B></div> <div> <IMG SRC="1559a8c0.gif" border=0 width="154" height="140" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> </NOBR></tD> <tD VALIGN=CENTER WIDTH="212"><div> One or a few dendrites radiate from cell body in a flat fan shape </div> </tD> <tD VALIGN=CENTER WIDTH="396"><div> Cerebellar Purkinje cells </div> </tD> </tR> </TABLE></div> <bR> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="669" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#000000 HEIGHT= 130 WIDTH="665"><div> Dendrites of some neurons are smooth, tapered processes, such as in motor neurons of the spinal cord. </div> <div> Other neurons exhibit enlargments, protrusions, or other structural specializations along dendrites, or frequently, at the ends of dendrites. </div> <div> These structures are often sites of synaptic contact and therefore can be referred to as <I>synaptic specializations</I></div> <bR> </tD> </tR> </TABLE></div> <bR> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="638" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" BGCOLOR=#FFFF00 > <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="184"><div> <B>Pattern </B></div> </tD> <tD VALIGN=CENTER WIDTH="274"><div> <B>Characteristics </B></div> </tD> <tD VALIGN=CENTER WIDTH="160"><div> <B>Examples </B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 38 WIDTH="184"><div> <B>Varicosity</B></div> <bR> </tD> <tD VALIGN=CENTER WIDTH="274"><div> An enlargment in a thinner dendrite associated with synaptic contacts </div> </tD> <tD VALIGN=CENTER><NOBR><div> Retinal amacrine cells </div> </NOBR></tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 38 WIDTH="184"><div> <B>Filopodium</B> </div> </tD> <tD VALIGN=CENTER WIDTH="274"><div> A long, thin protrusion with a dense actin matrix and few internal organelles </div> </tD> <tD VALIGN=CENTER WIDTH="160"><div> Normally only seen during development </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 131 ><NOBR><div> <B>Simple Spine:</B> Sessile</div> <bR> </NOBR></tD> <tD VALIGN=CENTER WIDTH="274"><div> Synaptic protrusions without a neck constriction</div> <bR> <bR> <div> Stubby spine</div> <bR> <div> Crook thorn </div> </tD> <tD VALIGN=CENTER WIDTH="160"><bR> <bR> <div> Pyramidal cells of cortex</div> <bR> <div> Cerebellar dentate nucleus </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 185 WIDTH="184"><div> <B>Simple Spine:</B> Pedunculated</div> <bR> </tD> <tD VALIGN=CENTER WIDTH="274"><div> Bulbous enlargement at tip</div> <bR> <bR> <div> Thin spine</div> <bR> <div> Mushroom spine</div> <bR> <div> Gemmule </div> </tD> <tD VALIGN=CENTER WIDTH="160"><bR> <bR> <div> Pyramidal cells of cortex</div> <bR> <div> Pyramidal cells of cortex</div> <bR> <div> Olfactory bulb granule cell </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 95 WIDTH="184"><div> <B>Branched Spine</B></div> <bR> </tD> <tD VALIGN=CENTER WIDTH="274"><div> Each branch has a unique presynaptic partner and each branch has the shape characteristics of a simple spine </div> </tD> <tD VALIGN=CENTER WIDTH="160"><div> CA1 pyramidal cells</div> <div> Granule cells of dentate gyrus</div> <div> Cerebellar Purkinje cells </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 76 WIDTH="184"><div> <B>Claw Ending</B></div> <bR> </tD> <tD VALIGN=CENTER WIDTH="274"><div> Synaptic protrusions at the tip of the dendrite associated with one or more glomeruli </div> </tD> <tD VALIGN=CENTER WIDTH="160"><div> Granule cells of cerebellar cortex and dorsal cochlear nucleus </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 76 WIDTH="184"><div> <B>Brush Ending</B></div> <bR> </tD> <tD VALIGN=CENTER WIDTH="274"><div> Spray of complex dendritic protrusions at the end of dendrite that extends into glomerulus and contains presynaptic elements </div> </tD> <tD VALIGN=CENTER WIDTH="160"><div> Unipolar brush cells of cerebellar cortex and dorsal cochlear nucleus </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 76 ><NOBR><div> <B>Thorny Excrescence</B></div> <bR> </NOBR></tD> <tD VALIGN=CENTER WIDTH="274"><div> Densely lobed dendritic protrusion into a glomerulus </div> </tD> <tD VALIGN=CENTER WIDTH="160"><div> Proximal dendrites of CA3 pyramidal cells and dentate gyrus mossy cells </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 57 ><NOBR><div> <B>Racemose Appendage</B></div> <bR> </NOBR></tD> <tD VALIGN=CENTER WIDTH="274"><div> Twig-like branched dendritic appendages that contain synaptic varicosities and bulbous tips </div> </tD> <tD VALIGN=CENTER WIDTH="160"><div> Inferior olive</div> <div> Relay cells of lateral geniculate nucleus </div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 76 ><NOBR><div> <B>Coralline Excrescence</B></div> <bR> </NOBR></tD> <tD VALIGN=CENTER WIDTH="274"><div> Dendritic varicosity extending numerous thin protrusions, velamentous expansions and tendrils </div> </tD> <tD VALIGN=CENTER WIDTH="160"><div> Cerebellar dentate nucleus</div> <div> Lateral vestibular nucleus </div> </tD> </tR> </TABLE></div> <bR> <div> <TABLE BORDER="0" CELLPADDING="1" CELLSPACING="1" WIDTH="226" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="VOID" RULES="NONE" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER BGCOLOR=#000000 HEIGHT= 16 WIDTH="222"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="16" ALIGN="bottom" WIDTH="222" HSPACE="0" VSPACE="0"></tD> </tR> </TABLE></div> <div> <IMG SRC="15693940.jpg" border=0 width="659" height="404" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <div> Perhaps the most common synaptic specialization of dendrites is that which Spanish anatomist Ramon y Cajal referred to as "espinas", since they resembled the thorns on a flower stem. These <I>spines</I> are frequent on the dendrites of the principal cells of most brain regions, notably on the pyramidal cells of cerebral cortex and the Purkinje cells of the cerebellar cortex. For these cells, more than 90% of their excitatory <FONT SIZE="3" COLOR="#800000" FACE="Arial" >synapse</FONT>s occur on dendritic spines. Therefore, spines may play an important role in learning and memory. </div> <div> Simple spines are very small, often less than 1 micron in diameter. This makes them difficult to study through light microscopy. Electron microscopy must be used to determine the geometry of spines.</div> <bR> <div> <B><IMG SRC="15780000.jpg" border=0 width="640" height="512" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="158d9a50.jpg" border=0 width="473" height="421" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="15980400.jpg" border=0 width="640" height="320" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="15a40f00.gif" border=0 width="320" height="240" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="15ddf440.gif" border=0 width="479" height="324" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></B></div> <bR> <bR> <bR> <div> <B><U>ASTROCYTES</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B><U> </U></B></FONT></div> <bR> <div> <IMG SRC="177014b0.gif" border=0 width="513" height="331" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="178dbe20.gif" border=0 width="731" height="482" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="179dee50.gif" border=0 width="734" height="485" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Astrocytes (star cells) have radially arranged processes. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Their cytoplasm contains intermediate filaments composed of a distinct protein, <B>glial fibrillary acidic protein</B> <B>(GFAP)</B>. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Antibodies against this protein are routinely used to demonstrate reactive and neoplastic astrocytes. Historically, <B><U>GFAP was the first immunostain to be used</U></B></div> <div> <IMG SRC="0a808990.gif" border=0 width="520" height="409" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><FONT SIZE="3" COLOR="#000000" FACE="System" >Astrocytes around blood vessel. GFAP immunostain.</FONT><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Astrocytes are important for <B>structural support</B> of the CNS.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000008000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Astrocytes<FONT SIZE="3" COLOR="#000000" FACE="Arial" > can be identified at the ultrastructural level by a number of key structural features: </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">an irregular, stellate shape</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">numerous glycogen granules</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">bundles of intermediate filaments</U><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f0ff000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">a relatively clear cytoplasm </U></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000008000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Astrocytes<FONT SIZE="3" COLOR="#000000" FACE="Arial" >, like other glial subtypes, have been commonly thought of as mere support and maintenance cells for the real actors in brain functioning, the neurons.</FONT></div> <div> <IMG SRC="161f42a0.gif" border=0 width="500" height="298" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Their processes form the <B><U>glia limitans</U></B><U>,</U> a membrane that seals the external surface of the CNS. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">During brain development, astrocytic processes (<B>radial glia</B>) guide neurons in their migration from the wall of the ventricles to the cortex.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Astrocytic foot processes surround brain capillaries and, during development, induce endothelial cells to form tight junctions. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The endothelial tight junctions are the basis of the <B>blood-brain barrier</B>, a system of controlled transcapillary transport which maintains homeostasis in the CNS.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Endothelial tight junctions are found only in brain capillaries. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Loss of the integrity of the endothelial barrier causes fluid to leak into the interstitial space, leading to <B>vasogenic cerebral edema</B>.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> This raises intracranial pressure and can collapse brain capillaries, resulting in arrest of cerebral perfusion.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Cerebral edema is caused by a variety of pathological processes, including ischemic insults, inflammation, and malignant brain tumors whose capillaries do not have tight junctions. </div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Astrocytes are less vulnerable than neurons to ischemic injury but they are damaged if there is lactic acidosis.</U></B><FONT SIZE="3" COLOR="#000000" FACE="Verdana" > </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Such damage causes intracellular fluid accumulation<B> (cytotoxic edema)</B>.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Cytotoxic edema involves the cerebral cortex, whereas vasogenic edema is more pronounced in the white matter. </div> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Vasogenic edema is more important clinically than cytotoxic edema.</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <IMG SRC="162a32e0.gif" border=0 width="675" height="302" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="1632c110.gif" border=0 width="300" height="273" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="164a30a0.gif" border=0 width="675" height="266" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <bR> <div> <B><U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Astrocytes are important for regulation of metabolic activities of neurons</U></B>. </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They take up GABA and glutamate that are released at synaptic clefts and convert them to glutamine. Glutamine is then transferred to neurons and recycled into GABA and glutamate</B>. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Astrocytes are also important for <B>maintaining proper ionic balance in the extracellular fluid.</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">When neurons are lost and brain tissue is damaged from whatever cause, astrocytes proliferate, fill the gaps, and restore CSF-brain and blood-brain barriers.</B> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This process, which is called <B>gliosis</B>, is for the CNS what scarring is for extraneural tissues.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Astrocytes participating in gliosis are referred to as<B> reactive astrocytes</B>. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They have a large cytoplasmic mass, long, branching processes, and increased cytoplasmic filaments.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Such astrocytes are also known as<B><U> </U></B><B><U>gemistocytic astrocytes </U></B><B><U>from a Greek word that means to fill up.</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B><U> </U></B></FONT></div> <div> <B><U><IMG SRC="15e90c40.jpg" border=0 width="400" height="452" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></U></B><FONT SIZE="2" COLOR="#800000" FACE="Arial" >astrocytes</FONT><FONT SIZE="2" COLOR="#008080" FACE="Arial" >, appear to talk to neurons and affect their ability to signal with each other. This suggests that they may influence the brain's thinking process.</FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000008000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">astrocytes<FONT SIZE="3" COLOR="#000000" FACE="Arial" > develop an ability to modulate the extracellular neuronal environment, and in mature CNS tissue manifest a capacity for active uptake of amino acids and ions. </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000008000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Astrocytes<FONT SIZE="3" COLOR="#000000" FACE="Arial" > can control extracellular volume by regulation of their own volume, and are intimately involved in the neuronal exchange of trophic substances and metabolites. </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Astrocytic processes extend to blood vessel walls, the brain surface, the ventricular wall, neuronal cell bodies and synapses. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000008000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Astrocytes<FONT SIZE="3" COLOR="#000000" FACE="Arial" > are abundantly supplied with membrane receptors for varoius neurotransmitters, coupled to such second messenger systems as cyclic AMP (adenosine monophosphate) or the phosphatidylinositol cycle. </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Activation of the receptors results in changes in oxidative metabolism, cell morphology, cell volume, and immunocompetence: and recent findings have shown the occurrence of receptor-mediated changes in amino acid uptake.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Thus, by modulating the extracellular environment, <FONT SIZE="3" COLOR="#800000" FACE="Arial" >astrocytes</FONT> can simultaneously modulate the sensitivity and/or excitability of large numbers of neurons. In the article are presented recent research findings suggesting astroglial cells to be targets for neurotransmitters, and probably to be actively involved in higher cognitive functions.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Advances in our knowledge of astroglial cell characteristics might improve our understanding of behavioural disturbances and disease of the CNS." </div> <div> <B><U><IMG SRC="15f8e900.jpg" border=0 width="142" height="144" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="160c3e00.jpg" border=0 width="451" height="224" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></U></B></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">I<B>n acute metabolic disorders such as hepatic encephalopathy, hyperammonemia, and cerebral ischemia, astrocytes enlarge. Their nuclei are large and appear clear in H&E stains</B>.</div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In hyperammonemia, they also accumulate glycogen. Such cells are called Alzheimer type II astrocytes. This probably reflects a poorly understood role of astrocytes in metabolic dysfunction. </B><B>Rosenthal fibers</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> </B></FONT><B>and </B><B>corpora amylacea</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B> .</B></FONT><B>are products of astrocytes</B>.</div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> </B><B>Rosenthal fibers</B><B> are homogeneous, eosinophilic, elongated or globular cytoplasmic inclusions</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">. <FONT SIZE="3" COLOR="#FF0000" FACE="Verdana" ><B>They are seen in old brain scars dating back to childhood, and in some low-grade astrocytomas. </B></FONT></div> <bR> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Corpora amylacea</B> are spherical intracytoplasmic bodies of carbohydrate polymers that develop in astrocytic processes with advancing age. </div> <div> <U><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They have no pathological significance.</U></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The astrocyte is the cell in the adult mammalian brain most capable of undergoing mitosis. </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Most brain tumors are derived from astrocytes (</B><B>astrocytomas</B><B>)</B>.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <FONT SIZE="2" COLOR="#000000" FACE="Arial" ><B><U><IMG SRC="16755e20.jpg" border=0 width="341" height="226" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></U></B></FONT>Astrocytes<FONT SIZE="3" COLOR="#000000" FACE="Arial" > are distinguished by their large stellate-shaped cell bodies and many radiating processes. Some of these processes form terminal expansions (arrows) that are applied to the surface of blood vessels. (Bv). Fibrous </FONT>astrocytes<FONT SIZE="3" COLOR="#000000" FACE="Arial" > (f) are less branched and their processes radiate from the cell body for considerable distances whereas protoplasmic </FONT>astrocytes<FONT SIZE="3" COLOR="#000000" FACE="Arial" > (P) have more numerous and profusely branched processes</FONT></div> <div> <FONT SIZE="2" COLOR="#000000" FACE="Arial" ><B><U><IMG SRC="168c24e0.jpg" border=0 width="450" height="590" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></U></B></FONT>The nucleus and cytoplasm of <FONT SIZE="3" COLOR="#800000" FACE="Arial" >astrocytes</FONT> is lighter in appearance than most other cells. although the usual complement of cytoplasmic organelles are present, they are relatively sparse in the lucent cytoplasm. The include mitochondria (mit), microtubules (arrows), free ribosomes (r), short cisternae of granular endoplasmic reticulum (ER) and lysosomes (Ly). The most prominent cytoplasmic component is the numerous filaments (f) that extend into the processes. Note also that the outline of the astrocyte perikaryon is very irregular</div> <div> <B>Electrophysiological Hetergeneity</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <TABLE BORDER="2" CELLPADDING="1" CELLSPACING="1" WIDTH="634" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" ALIGN="BOTTOM" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=CENTER HEIGHT= 20 WIDTH="361"><div> <B>Passive</B></div> </tD> <tD VALIGN=CENTER WIDTH="258"><div> <B>Complext</B></div> </tD> </tR> <tR> <tD VALIGN=CENTER HEIGHT= 151 WIDTH="361"><div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Passive K+ current </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">No Na+ current </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Responsible for K+ accumulation (?) </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Nederground found only passive <FONT SIZE="3" COLOR="#800000" FACE="Arial" >astrocytes</FONT> </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Certain GFAP </div> </tD> <tD VALIGN=CENTER WIDTH="258"><div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">3 types of the K+ current: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A-type </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Outward delayed rectifier </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Inward rectifier</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">EGTA converts to passive type </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Little or no GFAP</div> </tD> </tR> </TABLE></div> <div> <B>Possible Roles of Complex </B><FONT SIZE="4" COLOR="#800000" FACE="Arial" ><B>Astrocytes</B></FONT><FONT SIZE="3" COLOR="#000000" FACE="Arial" > <IMG SRC="16ae4190.gif" border=0 width="228" height="281" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="16bfe870.gif" border=0 width="254" height="135" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="16c00be0.gif" border=0 width="256" height="190" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Precursor calls that proliferate following inquiry </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Voltage-dependent K+ channel trigger proliferation </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">No evidence</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Potassium Homeostasis </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Some suggest that complex <FONT SIZE="3" COLOR="#800000" FACE="Arial" >astrocytes</FONT> are better suited for K+ uptake </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Blocking voltage-actived K+ channel in CA1 hampered K+ clearance and neuronal activity</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Monitoring Synaptic Activity </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Depolarization ? lead to Ca++ influx through voltage activated channels </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">No evidence (metabotropic glutamate receptors)</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Voltage-depend Na+ channel </div> <bR> <div> <B><U><IMG SRC="16973800.jpg" border=0 width="115" height="128" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="16d2cde0.gif" border=0 width="300" height="222" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></U></B></div> <div> <B><U>Does Minor Head Trauma Create Nonsense Calcium Waves?</U></B></div> <div> Equally mysterious are the mechanisms producing unconsciousness resulting from minor head trauma insufficient in force to cause any detectable injury. Mechanical perturbation has been shown to precipitate calcium waves in vitro (20). A blow to the head results in a mechanical compression wave traveling through the brain. This mechanical force could be sufficient to produce a pattern of widespread sequential calcium waves that reflect the shape and velocity of the mechanical compression wave. The astrocytic calcium waves so produced would be unrelated to, and for a while unresponsive to the influence of, normal sensory input. Meaningful interactions between <FONT SIZE="3" COLOR="#800000" FACE="Arial" >astrocytes</FONT> and synapses could be overwhelmed by the disruptively nonsensical mechanically induced calcium wave patterns. Despite the inability of the mechanical force to produce macro or microscopic injury, the brain -- the person -- would be "knocked out" or temporarily unconscious. </div> <bR> <bR> <div> <B><U>Do General Anesthetics Work by Blocking Astrocytic Gap Junctions?</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> A similar unconscious state in which the cellular elements of associative cortex cannot respond normally to sensory input could, according to the theory, result from astrocytic gap junction blockade. Without functional gap junctions, <FONT SIZE="3" COLOR="#800000" FACE="Arial" >astrocytes</FONT> become unable to transmit their control of synchronous synaptic firing through the cortex. Because <FONT SIZE="3" COLOR="#800000" FACE="Arial" >astrocytes</FONT> cannot form syncytia, their control is restricted to only the synapses within their individual domains of influence. Several general anesthetics have been demonstrated to be reversible gap junction blockers  </div> <bR> <bR> <div> <B><U>Does Memory Depend on the Neuron-Astrocyte Relationship?</U></B></div> <div> Many authors have speculated on the involvement of <FONT SIZE="3" COLOR="#800000" FACE="Arial" >astrocytes</FONT> in memory and CNS plasticity. The neuron-astrocyte theory here, however, proposes that the infotropic character of <FONT SIZE="3" COLOR="#800000" FACE="Arial" >astrocytes</FONT> is crucial to the cellular basis of associative memory. Also, <I>neuroplasticity</I> may more properly be termed <I>neuronal-astrocytic plasticity</I>, with the <FONT SIZE="3" COLOR="#800000" FACE="Arial" >astrocytes</FONT>' capacity to influence groups of synapses compromised only by the degree to which they have already organized these groups. Biological imprinting that occurs within defined critical periods of many species might represent a more permanent infotropically mediated astrocytic organization of synaptic domains. This premise is supported by the work of Muller and Best who reinduced ocular-dominance plasticity in adult animals by supplementing the adult visual cortex with <FONT SIZE="3" COLOR="#800000" FACE="Arial" >astrocytes</FONT> cultured from the visual cortex of newborn animals. </div> <div> <B><U>Concluding</U></B></div> <div> <B><U>Remarks</U></B></div> <div> The neuron-astrocyte theory challenges the notion that neuronal networks alone, no matter how complex, can explain the many normal and pathological aspects of brain function. This model, in which motile <FONT SIZE="3" COLOR="#800000" FACE="Arial" >astrocytes</FONT> organize and modulate synaptic activity, may permit widely divergent aspects of brain function and pathology to be viewed from a single theoretical vantage. Testing key aspects of this theory, i.e., astrocytic movement in vivo and astrocytic control of neurotransmission in vivo, will present significant technical challenges. When these challenges are overcome, however, we may learn significant new lessons about cortical function, its cellular substrates, and the mechanisms by which it is compromised in a variety of disease states. </div> <bR> <bR> <div> <B>OLIGODENDROGLIA</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Myelin</B> is a sheath of plasma membrane wrapped around axons</div> <div> 1. The <FONT SIZE="2" COLOR="#0000FF" FACE="arial" ><U>non-neural cells</U></FONT> of the <FONT SIZE="2" COLOR="#0000FF" FACE="arial" ><U>ectodermal</U></FONT> origin forming part of the <FONT SIZE="2" COLOR="#0000FF" FACE="arial" ><U>adventitial structure</U></FONT> (<FONT SIZE="2" COLOR="#0000FF" FACE="arial" ><U>neuroglia</U></FONT>) of the <FONT SIZE="2" COLOR="#0000FF" FACE="arial" ><U>central nervous system</U></FONT>; projections of the surface <FONT SIZE="2" COLOR="#0000FF" FACE="arial" ><U>membrane</U></FONT> of each of these <FONT SIZE="2" COLOR="#0000FF" FACE="arial" ><U>cells</U></FONT> (<FONT SIZE="2" COLOR="#0000FF" FACE="arial" ><U>oligodendrocytes</U></FONT>) fan out and coil around the <FONT SIZE="2" COLOR="#0000FF" FACE="arial" ><U>axon</U></FONT> of many <FONT SIZE="2" COLOR="#0000FF" FACE="arial" ><U>neurons</U></FONT> to form <FONT SIZE="2" COLOR="#0000FF" FACE="arial" ><U>myelin sheaths</U></FONT> in the <FONT SIZE="2" COLOR="#0000FF" FACE="arial" ><U>white matter</U></FONT>. With <FONT SIZE="2" COLOR="#0000FF" FACE="arial" ><U>microglia</U></FONT>, they form the <FONT SIZE="2" COLOR="#0000FF" FACE="arial" ><U>perineuronal satellites</U></FONT> in the <FONT SIZE="2" COLOR="#0000FF" FACE="arial" ><U>gray matter</U></FONT>. </div> <div> 2. The <FONT SIZE="2" COLOR="#0000FF" FACE="arial" ><U>tissue</U></FONT> composed of such cells.</div> <bR> <bR> <div> <IMG SRC="0aa08c00.gif" border=0 width="520" height="448" ALIGN="BOTTOM" HSPACE="0" VSPACE="0">Myelin: Layers of plasma membrane wrapped around an axon</div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Its insulating properties are important for conductivity. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">It consists of 70-80 percent lipids and 20 percent structural proteins, including<B> Proteolipid Protein, Myelin Basic Protein and Myelin Associated Glycoprotein.</B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In the CNS, myelin is made by oligodendroglial cells; in peripheral nerves by Schwann cells.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Each Schwann cell makes one segment of myelin; each oligodendrocyte makes multiple segments of myelin that wrap around several axons.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Most myelin stains use mordant-hematoxylin solutions that attach to phospholipid components of the myelin sheath and give myelin a deep blue color.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Myelin and oligodendrocytes are non-specifically lost in cerebral infarcts, infections, and other lesions that involve the white matter. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">More specific loss occurs in <B>demyelinative disorders</B>, such as <B>multiple</B><FONT SIZE="3" COLOR="#000080" FACE="Verdana" ><B> </B></FONT><B>sclerosis</B> and <B>progressive</B><FONT SIZE="3" COLOR="#000080" FACE="Verdana" ><B> </B></FONT><B>multifocal leukoencephalopathy</B> (<B>PML</B>). </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">PML is caused by a papovavirus infection of oligodendrocytes.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Myelin proteins are immunogenic, and some aspects of inflammatory demyelinative disorders are due to autoimmunity.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> <B>Leukodystrophies </B>are metabolic disorders caused by biochemical abnormalities of myelin lipids</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> They show diffuse and progressive loss of myelin. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The term "degeneration" in reference to myelin means loss of myelin; in reference to the white matter or specific tracts (e.g. posterior colum degeneration), it means loss of myelin and axons.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700c800008000.gif" HEIGHT="13" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Oligodendroglia Pathology In Multiple Sclerosis</div> <bR> <div> <IMG SRC="1722bac0.jpg" border=0 width="299" height="428" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <div> <B><U>EPENDYMA</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B><U> </U></B></FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The ependymal cells line the walls of the ventricles and form the specialized choroid plexus epithelium which secretes the cerebrospinal fluid (CSF).</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The ependymal lining may be injured and lost as a result of infections involving the cerebral ventricles (ventriculitis) and intraventricular hemorrhage.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Residual ependymal cells proliferate and form tubules (rosettes) and small nodules with admixed reactive astrocytes (ependymal granulations) in the walls of the ventricles</div> <bR> <bR> <div> <B><U>There are several kinds of glia</U></B><B><U> </U></B></div> <bR> <div> 1. Glia that forms myelin eg. </div> <div> CNS: <FONT SIZE="3" COLOR="#800000" FACE="Arial" ><U>oligodendroglia</U></FONT> </div> <div> PNS: Schwann cells </div> <div> 2. Glia that form structural support and buffer extracellular ions </div> <div> eg. <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>astroglia</U></FONT> </div> <div> 3. Glia that phhagocytose dying and injured cells </div> <div> eg. <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>microglia</U></FONT> </div> <div> 4. Glia that provide scaffolds for migrating neurons and processes </div> <div> eg. <FONT SIZE="3" COLOR="#0000FF" FACE="Arial" ><U>Radial</U></FONT> glia </div> <bR> <div> <B>MICROGLIA</B><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <IMG SRC="17ad9e50.gif" border=0 width="729" height="485" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><IMG SRC="17cc6c50.gif" border=0 width="710" height="453" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Microglial cells are the histiocytes of brain tissue.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> They migrate into the developing brain together with blood vessels.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Unlike neurons and other glial cells which are neuroectodermal, microglial cells are derived from mesoderm.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> They are distributed diffusely in the brain.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> They share cellular markers with blood monocytes and tissue histiocytes.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> They act as scavenger cells, similar to histiocytes of other tissues, and participate in immune-inflammatory reactions in the brain.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> When brain injury is associated with vascular disruption such as in an infarct or contusion, blood borne monocytes enter the lesion, and then internalize, degrade, and remove the dead tissue. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">After this phagocytosis, the cytoplasm of these monocytes enlarges and becomes foamy or granular from lipid and other products that are generated.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> These cells are called <B>macrophages</B>.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <bR> <div> <IMG SRC="0ac08a70.gif" border=0 width="520" height="423" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><FONT SIZE="3" COLOR="#000000" FACE="Arial" >Macrophages in a cerebral infarct. These cells are derived from blood monocytes</FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">When brain tissue breaks down but vessels remain intact, e.g. in Alzheimer disease, phagocytosis is performed by indigenous microglial cells.<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In addition to their phagocytic activity, microglial cells play an important role in immune reactions in the CNS. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They collaborate in this function with lymphocytes that traffic through the subarachnoid space and perivascular spaces. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Microglial cells can sense damaged tissue and have receptors that enable them to recognize viruses and other immunogens.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Such recognition leads to upregulation of microglial cells and synthesis of cytokines intended to destroy foreign antigens. Resting microglial cells are inconspicuous.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> They have a small elongated nucleus and indistinct cytoplasm. For a long time, there was even doubt whether they represented a distinct cell population. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Their existence was eventually confirmed when immunohistochemistry revealed cellular markers that align microglial cells with monocytes.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Upregulated (activated) microglial cells have large rod-shaped nuclei. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">They infiltrate brain tissue diffusely, encircle dead neurons (<B>neuronophagia</B>),<FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT>or form small clusters (<B>microglial nodules</B>) around small foci of dead brain tissue</div> <bR> <div> <IMG SRC="0aee1350.gif" border=0 width="481" height="309" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"><FONT SIZE="3" COLOR="#000000" FACE="Arial" >Microglial nodule</FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Microglial nodules are the hallmark of viral encephalitis but are also seen in other infections and in noninfectious conditions such as hypoxic-ischemic encephalopathy, Wernig-Hoffmann disease, and neuronopathic Gaucher disease. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Microglial cells have <B><U>T4 receptors and are susceptible to HIV infection</U></B>. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">However, HIV is probably brought into the brain by infected lymphocytes and monocytes.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Ingestion of HIV-carrying lymphocytes by microglial cells probably propagates the infection in the brain. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The inflammatory cytokines that are produced by microglial cells are intended to kill viruses and other pathogens but damage also brain cells and myelin.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> This contributes to the brain damage from viral encephalitis, multiple sclerosis, and <B>HIV encephalitis</B></div> <bR> <bR> <div> <B><U>TISSUE PATTERNS</U></B><FONT SIZE="3" COLOR="#000000" FACE="Arial" ><B><U> </U></B></FONT></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Neurons and glial cells are arranged in varying patterns in different parts of the CNS. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In the cerebrum and cerebellum, the cell bodies and dendrites of neurons are on the surface (<B>cerebral cortex</B>: shell) and their myelinated axons (<B>white matter</B>) in the internal part of the hemispheres. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The spinal cord has the opposite design: the neuronal cell bodies (anterior and posterior horns) are in the center and the white matter at the periphery. </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The white matter of the cerebral hemispheres and spinal cord consists of myelin, oligodendroglia, astrocytes, microglia, and blood vessels</B>. It contains no neurons. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The central portion of the cerebral hemispheres (basal ganglia - diencephalon) and the brainstem contain several masses of neurons (nuclei) that are intimately mixed with white matter.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> <FONT SIZE="3" COLOR="#000000" FACE="Verdana" >In most of the cerebral cortex (neocortex), neurons are arranged in five layers with a sixth layer consisting of synapses on the surface. </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These five layers contain mainly two types of neurons,</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> <B>pyramidal cells</B> (large neurons with an apical dendrite and a long axon) <FONT SIZE="3" COLOR="#000000" FACE="Arial" ><IMG SRC="17e728c0.gif" border=0 width="626" height="396" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></FONT></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">stellate or granule cells</B> (smaller neurons with many dendrites and short axons). </div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Pyramidal cells project their axons to targets away from their points of origin. </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Stellate cells receive afferents and form intracortical networks. </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Pyramidal cells are found in layers 3, 5, and 6 and stellate cells mainly in layers 2 and 4. </B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The mix of pyramidal and stellate cells varies in different cortical fields and correlates with cortical function.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In the medial edge of the temporal lobes, the neuronal layers are reduced to two,one pyramidal and one granular (the dentate gyrus).</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These layers are wound around one another and form a structure that is called <B>hippocampus</B> (sea horse) or Ammon's horn because of its peculiar shape.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> <FONT SIZE="3" COLOR="#000000" FACE="Verdana" >The subiculum and entorhinal cortex are interposd between the hippocampus and the temporal neocortex. </FONT></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The hippocampus receives extensive afferents from association cortex and limbic areas, and projects to the thalamus, hypothalamus, and cortex. </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The hippocampus is important for the process of declarative memory,</B> i.e. the memory for facts and events, but is not a storage depot for old memories. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">These are stored at multiple sites in the neocortex.</div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f00000ff00.gif" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Bilateral lesions of the hippocampus (and medial dorsal nucleus of the thalamus) cause </B><B>Korsakoff amnesia</B><FONT SIZE="3" COLOR="#000000" FACE="Verdana" >, a disorder characterized by inability to remember new things with relative preserrvation of established memories.</FONT><FONT SIZE="3" COLOR="#000000" FACE="Arial" > </FONT></div> <div>  <A NAME="navigation"><IMG BORDER="0" SRC="1x1.gif" HEIGHT="1" ALIGN="bottom" WIDTH="1" HSPACE="0" VSPACE="0" ></A></div> <bR> <bR> <bR> </td> </tr></table></body>