Neurohistology

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

This article has some overlap with the neuroanatomy article, as there isn't a clear divider between microscopic and macroscopic.

Normal cells

This section deals with normal cellular constituents of the CNS.

Overview

Central nervous system

Neuron

  • Abundant cytoplasm - key feature.
  • Often very large cells, with angled edges.
  • Prominent nucleolus.
  • Nissl substance (granular perinuclear material = rough endoplasmic reticulum).

Glial cells

  • Oligodendrocyte.
    • Small round nuclei (lymphocyte-like nucleus) - key feature.
    • May resemble a fried egg on H&E (clear cytoplasm, central nucleus).
  • Astrocyte.
  • Microglia - macrophage of the brain (derived from monocyte).
    • Typically large cells with abundant cytoplasm.
      • Often have vesicles.
    • Rarely seen in normal tissue.
  • Ependyma.

Peripheral nervous system

Ganglion cell

  • Nerve cell body.
  • Found in ganglions - encapsulated body ~ 100-300 μm.
  • Large round nucleus with prominent nucleolus - key feature.
  • Abundant eosinophilic granular cytoplasm.

Image:

Normal cellular constituents in a table

Cell Key feature Other features Image
Neuron cytoplasm Nissl substance (prominent
RER), "sharp" corners
in cell membrane, nucleolus
- usu. prominent[1]
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
typically have a sharply
demarcated bubbly cytoplasm;
rarely seen in normal tissue
(neuropathologyweb.org),
(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.[2]
  • Polygonal shape.
  • Send dendrites in all directions.

Images:

Structures

This section deals with structures seen at several places in the CNS.

Grey vs. white matter

Grey matter White matter
Definition neurons present neurons absent
Extracellular
space (neuropil)
dense - darker pink (on H&E/HPS) fine mesh - lighter pink (on H&E/HPS)
Image right 2/3 of image left 1/3 of image

Additional images (white matter vs. grey matter):

Vessels

The small blood vessels in the CNS are separated from the surrounding tissue in histologic sections. This is normal. The spaces are called Virchow-Robin spaces.[3]

Histology by anatomical structure

This section deals with specific anatomical structures.

Subependyma

Features:[4]

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

Caudate

Features:

  • Neurons with adjacent ependymal lining.[5]
    • The caudate forms lateral wall of lateral ventricle.

Notes:

  • Caudate, putamen and nucleus accumbens are collectively called neostriatum.[6]

Putamen

Features:

  • Striatopallidal fibers AKA pencils of Wilson (also pencil fibers of Wilson[6] and Wilson's pencils[7]) - bundles of blue fibres (on H&E LFB).
  • Neurons:
    1. Small - GABA.
    2. Large (very rare: ~1 in 100-200) - cholingeric.

Images:

Notes:

  • Histologically identical to the caudate - but not adjacent to a ventricle.
    • The caudate is adjacent to an ependymal lined space, putamen is not.[8]
  • Necrotic putamen in methanol poisoning.[9]

Globus pallidus

  • AKA paleostriatum.[10]
  • Location:
    • Superior of the substantia innominata.
    • Medial to the putamen.

Features:

  • Histologically distinct from caudate and putamen.

Image: Globus pallidus, putamen and the nucleus basalis in the substantia innominata - very low mag. (WC).

Hippocampus

Structures

Hippocampal formation:[11]

  1. Dentate gyrus.
  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.
      • No vacuolated looking stuff next to it.

Images:

Important notes:

  • CA1 - weak link, dies in ischemia, affected by hypoglycemia, degenerative diseases and toxins.
  • CA2 - resistant to ischemia.
  • CA4 - involved in epilepsy,[12] usu. normal in degenerative diseases.[13]

Layers of CA[14]

  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:

Dentate nucleus

Features:[15]

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

Images:

Cerebellar cortex

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".[17]

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) that are grossly identified as the line of Gennari.[18][19]
  5. Inner pyramidal layer.
    • Location of Betz neurons - large motor neurons of cerebral cortex.
  6. Multiforme layer (Polymorphic layer).

Images:

Cingulate cortex

  • Spindle neurons, AKA von Economo neurons.
    • Thought to be important in cognition and problem solving.[22]

Images:

Pineal gland

Features:[23][24]

  • 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:

Notes:

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

IHC

  • Synaptophysin +ve.[23]

Midbrain

Structures:

  • Substantia nigra (Parkinson's disease).
  • Nuclei of CN IV (posterior).
  • Nuclei of CN III (anterior).
  • Cerebral penduncles (anterior).
  • Red nuclei.

Schematics:

Pons

Features:

Locus ceruleus

Microscopic features:

  • Pigmented neurons.
    • Produce norepinephrine.

Notes:

Medulla oblongata

Anatomy

Schematic: Medulla oblongata - Gray's anatomy (WC).

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.[28]
  • CN X: 4th ventricle + lateral to nucleus of CN XII.

Image: Medulla oblongata - very low mag. (WC).

See also

References

  1. 1.0 1.1 Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 16. ISBN 978-0443069826.
  2. URL: http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1. Accessed on: 5 July 2010.
  3. URL: http://www.whonamedit.com/synd.cfm/43.html. Accessed on: 2 August 2011.
  4. Croul SE. 28 June 2010.
  5. URL: http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1. Accessed on: 2 July 2010.
  6. 6.0 6.1 Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 23-34. ISBN 978-0443069826.
  7. Kimura M, Kato M, Shimazaki H, Watanabe K, Matsumoto N (December 1996). "Neural information transferred from the putamen to the globus pallidus during learned movement in the monkey". J. Neurophysiol. 76 (6): 3771–86. PMID 8985875. http://jn.physiology.org/cgi/pmidlookup?view=long&pmid=8985875.
  8. URL: http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1. Accessed on: 22 December 2010.
  9. Bhatia, R.; Kumar, M.; Garg, A.; Nanda, A. (Dec 2008). "Putaminal necrosis due to methanol toxicity.". Pract Neurol 8 (6): 386-7. doi:10.1136/jnnp.2008.161976. PMID 19015300.
  10. Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 23. ISBN 978-0443069826.
  11. URL: http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1. Accessed on: 2 July 2010.
  12. Ingvar, M. (1986). "Cerebral blood flow and metabolic rate during seizures. Relationship to epileptic brain damage.". Ann N Y Acad Sci 462: 194-206. PMID 3518570.
  13. D. Munoz. 27 July 2011.
  14. Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 25. ISBN 978-0443069826.
  15. Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 27. ISBN 978-0443069826.
  16. URL: http://www.stonybrookmedicalcenter.org/pathology/neuropathology/chapter1. Accessed on: 2 July 2010.
  17. Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 18. ISBN 978-0443069826.
  18. Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 24. ISBN 978-0443069826.
  19. URL: http://www.ncbi.nlm.nih.gov/books/NBK11524/. Accessed on: 7 January 2011.
  20. URL: http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/N1-MS-01-01-Ans.htm and http://moon.ouhsc.edu/kfung/iacp-olp/apaq-text/n1-ms-01.htm. Accessed on: 31 October 2010.
  21. URL: http://www.ncbi.nlm.nih.gov/books/NBK11524/. Accessed on: 7 January 2011.
  22. Allman, JM.; Hakeem, A.; Erwin, JM.; Nimchinsky, E.; Hof, P. (May 2001). "The anterior cingulate cortex. The evolution of an interface between emotion and cognition.". Ann N Y Acad Sci 935: 107-17. PMID 11411161.
  23. 23.0 23.1 Perry, Arie; Brat, Daniel J. (2010). Practical Surgical Neuropathology: A Diagnostic Approach: A Volume in the Pattern Recognition series (1st ed.). Churchill Livingstone. pp. 25-26. ISBN 978-0443069826.
  24. 24.0 24.1 URL: http://www.lab.anhb.uwa.edu.au/mb140/corepages/endocrines/endocrin.htm. Accessed on: 31 October 2010.
  25. Croul SE. 28 June 2010.
  26. URL: http://www.med.univ-rennes1.fr/etud/pharmaco/media/alzheimerGB.htm#Locus%20coeruleus. Accessed on: 4 December 2010.
  27. Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 677. ISBN 978-1416054542.
  28. Crossman, Alan R.; Neary, David. (2010). Neuroanatomy: An Illustrated Colour Text (4th ed.). Churchill Livingstone. pp. 13. ISBN 978-0702030864.
  29. Miller VM, Kenny RA, Oakley AE, Hall R, Kalaria RN, Allan LM (August 2009). "Dorsal motor nucleus of vagus protein aggregates in Lewy body disease with autonomic dysfunction". Brain Res. 1286: 165–73. doi:10.1016/j.brainres.2009.05.083. PMID 19501577.

External links