Neurohistology: Neurons, Glia & Responses to Injury

Neurons and axonal transport

Nissl substance. Neurons are permanent cells whose basophilic Nissl bodies (stacked rough ER with free polyribosomes) fill the soma and dendrites. The axon hillock and axon contain none, so the hillock looks like a pale cone on Nissl (cresyl violet) stain and every axonal protein must be made in the soma and shipped outward.

Transport motors. Axonal microtubules point their plus ends toward the terminal. Kinesin moves cargo anterograde (soma → terminal); dynein moves it retrograde (terminal → soma). Fast transport of vesicles covers hundreds of mm/day, while slow transport of cytoskeletal proteins covers only a few mm/day. Retrograde passengers:

• Tetanus toxin: motor terminal → spinal inhibitory interneurons (e.g., Renshaw cells), where it blocks GABA and glycine release → spastic paralysis, trismus.
• Rabies virus: bite site → CNS; Negri bodies in hippocampal and Purkinje neurons.
• HSV and VZV: to sensory ganglia for latency; on reactivation they ride kinesin anterograde back to the skin, so recurrences return to the same site.
• Poliovirus: can reach anterior horn motor neurons this way.

Glial cells

Astrocytes. After any CNS injury they hypertrophy and proliferate (reactive gliosis); brain parenchyma heals with this glial scar rather than fibroblast collagen. In hyperammonemia (hepatic encephalopathy, Wilson disease) they swell into Alzheimer type II astrocytes while converting NH₃ to glutamine.

Microglia are the only glia not derived from ectoderm; they clear debris and cluster as microglial nodules in viral encephalitis. HIV infects CD4/CCR5-bearing microglia and macrophages (not neurons), which fuse into the multinucleated giant cells of HIV encephalitis.

One oligodendrocyte serves many axons, so its loss demyelinates many fibers at once; JC virus in PML lyses oligodendrocytes, while infected astrocytes merely look bizarre.

Barriers and circumventricular organs

Blood–brain barrier. Tight junctions between nonfenestrated capillary endothelial cells are the barrier proper, backed by basement membrane and astrocyte end-feet. Lipid-soluble molecules diffuse; glucose needs GLUT1 and neutral amino acids need LAT1. Levodopa rides LAT1, whereas dopamine cannot cross. Tumors, abscesses and infarcts break the junctions → vasogenic edema and contrast enhancement.

Choroid plexus. Ependymal cilia propel CSF and microvilli absorb it. Choroid plexus (modified ependyma over fenestrated capillaries) secretes ~500 mL of CSF daily; its epithelial tight junctions form the blood–CSF barrier. With only ~150 mL present at once, CSF turns over about three times a day, draining through arachnoid granulations into the dural venous sinuses.

Circumventricular organs have fenestrated capillaries so they can sample or secrete into blood:

• Area postrema (dorsal medulla): chemoreceptor trigger zone for vomiting, e.g., after cisplatin.
• OVLT: plasma osmolality → ADH and thirst; subfornical organ: angiotensin II → thirst.
• Median eminence, posterior pituitary (ADH, oxytocin) and pineal gland (melatonin): hormone release.

Neuronal responses to injury

Red neurons. Irreversible hypoxic-ischemic injury shows 12–24 h later: shrunken soma, intensely eosinophilic cytoplasm (Nissl lost), pyknotic nucleus, no nucleolus. Most vulnerable are hippocampal CA1 (Sommer sector) pyramidal cells, cerebellar Purkinje cells and neocortical layers 3, 5 and 6. Lost neurons are never replaced, only walled off by gliosis.

Axonal reaction (central chromatolysis). After axotomy the soma swells, the nucleus moves to the periphery, the nucleolus enlarges and Nissl disperses outward as protein synthesis rises for repair, best seen in anterior horn cells after peripheral nerve injury.

Wallerian degeneration. Distal to the cut, axon and myelin fragment and are cleared by macrophages; the proximal stump dies back only a node or two before sprouting. PNS Schwann cells proliferate inside the preserved endoneurial tubes (bands of Büngner) and guide the sprouts; a lesion 15 cm from its target needs roughly 5 months to reinnervate. CNS axons largely fail to regrow because of the glial scar, oligodendrocyte myelin inhibitors (e.g., Nogo) and slow debris clearance.

Sensory receptors and fiber types

Fibers. Rapid adapters report change and vibration; slow adapters report sustained pressure and stretch. All four mechanoreceptors use large myelinated Aβ fibers that ascend in the dorsal columns. Thinly myelinated Aδ fibers carry sharp, well-localized first pain and cold; unmyelinated C fibers (~0.5–2 m/s) carry dull, burning second pain, warmth and itch; both ascend in the spinothalamic tract.

A 128-Hz tuning fork tests large-fiber (Pacinian, Aβ) function; pinprick and temperature test small Aδ and C fibers.