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Cerebrum
Slide 76 (cerebrum, luxol blue/cresyl violet) [DigitalScope]
Slide 76b (toluidine blue & eosin) [DigitalScope]
  
The cerebral cortex is loosely stratified into layers containing scattered nuclei of both neurons and glial cells.  Examine the layered organization of the cerebral cortex using slide 76 stained with luxol blue/cresyl violet [ORIENTATION] (which stains white matter tracts and cell bodies) or toluidine blue and eosin [ORIENTATION] (TB&E, toluidine blue stains the nuclei and RER of cells whereas eosin stains membranes and axon tracts).  Typically one or more sulci (infoldings) will extend inward from one edge of the section.  Examine the gray matter on each side of the sulcus using first low and then high power.  Neurons of the cerebral cortex are of varying shapes and sizes, but the most obvious are pyramidal cells.  As the name implies, the cell body is shaped somewhat like a pyramid, with a large, branching dendrite extending from the apex of the pyramid toward the cortical surface, and with an axon extending downward from the base of the pyramid.  In addition to pyramidal cells, other nuclei seen in these sections may belong to other neurons or to glial cells also present in the cortex.  You may be able to see subtle differences in the distribution of cell types in rather loosely demarcated layers. There are 6 classically recognized layers of the cortex:

1. Outer plexiform (molecular) layer: sparse neurons and glia
2. Outer granular layer: small pyramidal and stellate neurons
3. Outer pyramidal layer: moderate sized pyramidal neurons (should be able to see these in either luxol blue or TB&E-stained sections)
4. Inner granular layer: densely packed stellate neurons (usually the numerous processes aren’t visible, but there are lots of nuclei reflecting the cell density)
5. Ganglionic or inner pyramidal layer: large pyramidal neurons (should be able to see these in either luxol blue or TB&E-stained sections)
6. Multiform cell layer: mixture of small pyramidal and stellate neurons

Pyramidal cells in layers III and V tend to be larger because their axons contribute to efferent projections that extend to other regions of the CNS –pyramidal neurons in layer V of motor cortices send projections all the way down to motor neurons in the spinal cord!

Deep to the gray matter of the cerebral cortex is the white matter that conveys myelinated fibers between different parts of the cortex and other regions of the CNS. Be sure you identify the white matter in both luxol blue and TB&E-stained sections, as it will appear differently in these two stains. Review the organization of gray and white matter in cerebral cortex vs. spinal cord.

NP004N hippocampal region, coronal section, luxol blue [DigitalScope]

This coronal section includes the hippocampus (hippocampus = sea horse), dentate gyrus, and adjacent temporal lobe gyrus (entorhinal cortex). Above the temporal (ventral or inferior) horn of the lateral ventricle the lateral geniculate nucleus is present. Lateral to this structure is the tail of the caudate. The medial surface of the section is the posterior portion of the thalamus and a small portion of the cerebral peduncle. Look at the margins of the ventricle at higher magnification and note that it is entirely lined by ependymal cells. Just medial (to the right) of the tail of the caudate, note the choroid plexus, which consists of highly convoluted and vascularized villi covered by ependymal cells which are specialized for the production of cerebrospinal fluid, or CSF.

The hippocampus and dentate gyrus function in what is known as the "limbic system" to integrate inputs from many parts of the nervous system into complicated behaviors such as learning, memory, and social interaction beyond the scope of what can be described here. For now, focus just on the morphology of these regions and observe the presence of three distinct layers rather than the six layers found in the cerebral cortex (evolutionarily speaking, the three-layered organization is considered to be "older," so this type of cortex is also known as "archicortex"). In the hippocampus [ORIENTATION], observe:

• ("1" in the orientation figure) a polymorphic layer containing many nerve fibers and small cell bodies of interneurons,
• ("2" in the orientation figure) a middle pyramidal cell layer containing hippocampal pyramidal cells, and
• ("3" in the orientation figure) a molecular layer containing dendrites of the pyramidal cells.

In the dentate gyrus [ORIENTATION], observe:

• ("4" in the orientation figure) a polymorphic layer containing nerve fibers (known as "mossy fibers") and cell bodies of interneurons,
• ("5" in the orientation figure) a middle granule cell layer containing the round, neuronal cell bodies of dentate granule cells , and
• ("6" in the orientation figure) a molecular layer containing dendrites of the granule cells.

There is a dramatic loss of parenchyma, manifested here by cortical atrophy and marked enlargement of the lateral ventricles (called hydrocephalus ex vacuo).

Patient's brain (left) with a normal brain (right). There is extensive widening of the sulci and narrowing of gyri in the patient's brain, indicative of substantial loss of brain parenchyma. (The color difference is due to the meningeal covering of the normal brain.)

On H&E stain, there are multiple ghost neurons with residual neurofibrillary tangles as well as viable neurons with tangles in the hippocampus. Overall, there is a decrease in viable neurons. In addition, there are scattered plaques. On Congo Red stain, amyloid can be seen in vessel walls. Tau immunostaining highlights many neurofibrillary tangles and plaques.