Neurohistology

This article covers basic (normal) neurohistology. It is essential to have a good grasp on neurohistology and neuroanatomy... before doing neuropathology.

Normal cells

• Neuron:
  • Abundant cytoplasm - key feature.
  • Often very large cells, with angled edges.
  • Prominent nucleolus.
  • Nissl substance (granular perinuclear material - rough ER).
• Glial cells.
  • Oligodendrocyte.
    • Small round nuclei (lymphocyte-like nucleus) - key feature.
    • May resemble a fried egg on H&E (clear cytoplasm, central nucleus).
  • Astrocyte.
    • Irregular non-ovoid nucleus - key feature.
    • Nuclei less dense than in oligodendrocyte.
    • Close to blood vessels.
    • Form blood-brain barrier.
    • Cytoplasm normally not visible.
    • Image: astrocyte (med.unsw.edu.au) (in endocrine development).
  • Microglia - macrophage of the brain (derived from monocyte).
    • May be large.
    • May have vesicles.
    • Rarely seen in normal tissue.
• Ependyma.
  • Simple ciliated cuboidal epithelium.
  • Image: Ependyma (stonybrookmedicalcenter.org).

Normal cellular constituents in a table

	Key feature	Other features	Image
Neuron	cytoplasm	Nissl substance (prominent RER), "sharp" corners in cell membrane, nucleolus - usu. prominent	red neurons (WC)
Astrocyte	non-ovoid nucleus	no cytoplasm	(unsw.edu)
Oligodendrocyte	round small nucleus	peri-nuclear clearing	(vetmed.vt.edu)
Microglia	rod-like shape, may have "bent" nucleus	rarely seen in normal tissue	(ucsf.edu),(vcu.edu)

Neurons

There are many types of 'em. Broadly, they can be classified as:

1. Pyramidal - have a pyramidal shape.
   1. Dentrites go to molecular layer.
   2. Axons go to outside of cortex.
2. Non-pyramidal.

Motor neurons:

• Coarse Nissl substance - key feature.
  • Nissl described as having a tigroid appearance.
• Polygonal shape.
• Send dendrites in all directions.

Image: Motor neuron (stonybrookmedicalcenter.org).

Histology by anatomical structure

Subependyma

Features:

• Ependyma (simple ciliated cuboidal epithelium).
• Subependymal plate - connective tissue with blood vessels.

Caudate

Features:

• Neurons with adjacent ependymal lining.
  • The caudate forms lateral wall of lateral ventricle.

Notes:

• Caudate, putamen and nucleus accumbens are collectively called neostriatum.

Putamen

Features:

• Histologically identical to the caudate - but not adjacent to a ventricle, i.e. an ependymal lining.
• Striatopallidal fibers AKA pencils of Wilson (also pencil fibers of Wilson and Wilson's pencils) - bundles of blue fibres (on H&E LFB).

Images:

• Globus pallidus & putamen - showing Wilson's pencils - very low mag. (WC).
• Putamen - intermed. mag. (WC).
• Pencils of Wilson (frontalcortex.com).

Globus pallidus

• AKA paleostriatum.

Features:

• Histologically distinct from caudate and putamen.

Hippocampus

Structures

Hippocampal formation:

1. Dentate gyrus.
   • "Dense" thin layer of nuclei.
   • Quasi "U-shaped"; "open" (top) portion of "U" is superolateral.
   • Image: Dentate gyrus (stonybrookmedicalcenter.org).
2. Hippocampus proper (AKA Ammon's horn) - this is subdivided:
   • Cornu ammonis 3 (CA3) - location: superior.
     • Large pyramidal neurons.
   • CA1 (AKA Sommer's sector) - location: inferior (next to subiculum).
     • Small dispersed pyramidal neurons.
   • CA2 - location: in between CA3 and CA1, lateral.
     • Narrow band of neurons between CA3 and CA1.
   • CA4 - location: medial (closest to dentate gyrus; CA4 sits in "open" part of "U").
3. Subiculum (AKA subicular complex).
   • Transitions to the six layers in the entorhinal cortex.

Images:

• Hippocampus - frontal section (WP).
• Hippocampus - good schematic (WC).
• Hippocampus (ajnr.org).
• Hippocampus and subiculum (hu-berlin.de).
• Hippocampus - crappy schematic (ucsd.edu).

Important notes:

• CA1 - weak link, dies in ischemia, affected by hypoglycemia, degenerative diseases and toxins.
• CA2 - resistant to ischemia.

Layers of CA

1. Molecular layer - opposed to the dentate gyrus (of Hippocampal formation).
2. Neurons (described above).
3. Alveus - opposed to the lateral ventricle.
   • Connects to the mammillary bodies via the fornix (circuit of Papez).

Cerebellum

Main components:

• Cortex (superficial) - branches (Christmas tree-like).
• Dentate nucleus (deep) - looks like the bite impression of a molar.
  • Image: Cerebellum, cortex & dendate nucleus - low power (stonybrookmedicalcenter.org).

Dentate nucleus

Features:

• Ribbon of grey matter.
  • Large neurons.
  • Small neurons.

Cerebellar cortex

• Layers (superficial to deep) - mnemonic MPG:
  1. Molecular layer -- "very pink" on H&E.
     • Inhibitory interneurons: stellate cells, basket cells.
  2. Purkinje cell layer.
     • One cell layer thick - hueuege cells (~50-80 micrometers).
       • Very large nucleus (~4x RBC diameter =~ 4x the size of granule cell).
         • Large nucleolus (~1x RBC diameter =~ size of granule cell).
  3. Granule cell layer -- "very blue" on H&E.
     • Granule cells (neurons) - majority of cells, small (~10 micrometres), round.
       • May look like small cell carcinoma to the uninitiated.
     • Golgi cells (interneurons) - few in number, elongated/columnar, 3-5x size of granule cell.
• Images:
  • Cerebellar cortex - micrograph (stonybrookmedicalcenter.org).
  • Cerebellar cortex - schematic (Gray's Anatomy - WC).

Notes:

• Bergmann glia are found between the molecular layer & granular layer. They are normally not seen. They are increased & prominent in pathologic states (e.g. ischemia); "Bergmann gliosis".

Cerebral cortex

Layers (superficial to deep):

1. Molecular layer.
   • Empty appearing.
2. Outer granular layer.
   • Higher cell density & smaller cells than pyramidal layer.
3. Outer pyramidal layer.
4. Inner granular layer.
   • Not prominent in frontal cortex.
   • Where the thalamic axons end.
   • Divided in three (a, b, c) in the calcarine cortex due to two white matter bands (external band of Baillarger, internal band of Baillarger) than are grossly identified as the line of Gennari.
     • Image: Calcarine cortex (ouhsc.edu).
5. Inner pyramidal layer.
   • Location of Betz neurons - large motor neurons of cerebral cortex.
6. Multiforme layer (Polymorphic layer).

Images:

• Cajal drawings - different areas (WC).
• Different stains (rice.edu).
• Cerebral cortex (williamcalvin.com).
• Cerebral cortex (benbest.com).

Pineal gland

Features:

• Cells in lobulated clusters or linear arrays (low power).
• Pinealocyte:
  • Light staining and round nuclei with neuroendocrine look (i.e. salt-and-pepper chromatin).
  • Broad rim of light cytoplasm.
• Astrocytes:
  • Cylindrical hyperchromatic nucleus ~ 1/2 the size of pinealocyte.

Images:

• Pineal gland (anhb.uwa.edu.au).
• Pineal gland - very high mag. (WC).
• Pineal gland - intermed. mag. (WC).
• Pineal gland - crappy (WC).

Notes:

• Highly cellular structure - may be confused with (metastatic) small cell carcinoma.
• Often calcified.

Midbrain

Structures:

• Substantia nigra (Parkinson's disease).
• Nucleus of CN IV.

Pons

Features:

• Looks like bacon (at very low power).
• Images:
  • Pons (stonybrookmedicalcenter.org).
  • Pons - intermed. mag. (WC).

Locus ceruleus

• Literally means blue spot.
• Location: adjacent to midline + anterior to 4th ventricle.

Features:

• Pigmented neurons.
  • Produce norepinephrine.

Medulla

Anterior

• Pyramids: adjacent to midline, anterior.
• Olives: lateral and posterior to pyramids.

Posterior - important nuclei (location)

• CN XII: 4th ventricle + adjacent to midline; medial to nucleus of CN X.
• CN X: 4th ventricle + lateral to nucleus of CN XII.

IHC

• Synaptophysin +ve.

See also

• Neuropathology.
• Muscle biopsy.
• CNS tumours.

External links

• Neuropathology micrographs - identifying the site (stonybrookmedicalcenter.org).
• Neural tissues - veterinary histology (vetmed.vt.edu).
• Basic neurohistology - quiz (ouhsc.edu).