Cellular Pathology of the Nervous System

Neuronal Responses - Neuron Under Siege

• Acute Neuronal Injury (Ischemic Cell Change):
  • "Red neurons": Eosinophilic cytoplasm, pyknotic nucleus, Nissl loss. Irreversible hypoxic/ischemic injury.
  • Cell body, nucleus, nucleolus shrink.

  ⭐ Red neurons are visible by LM approx. 12‑24 hours post irreversible hypoxic/ischemic insult.

• Subacute & Chronic Neuronal Injury (Degeneration):
  • Selective neuronal loss; reactive gliosis (astrocytosis).
  • Apoptosis or necrosis.
• Axonal Reaction (Central Chromatolysis):
  • Response to axonal injury.
  • Cell body swells; Nissl disperses peripherally; nucleus eccentric.
• Neuronal Inclusions:
  • Markers of aging, viral infections, neurodegenerative diseases.
  • E.g., Lipofuscin (aging), Negri bodies (Rabies), Cowdry bodies (HSV), Lewy bodies (Parkinson's), Neurofibrillary tangles (Alzheimer's).

Glial Reactions - Support Crew's Crisis

• Astrocytes (Astrogliosis/Gliosis): Key CNS injury responders; form glial scars.
  • Hypertrophy & hyperplasia; ↑ GFAP.
  • Gemistocytic astrocytes: reactive; plump, eosinophilic cytoplasm, eccentric nucleus.
  • Corpora amylacea: PAS+, basophilic, laminated polyglucosan bodies; age-related or chronic conditions.
  • Alzheimer type II astrocytes: large, clear nucleus (NOT Alzheimer's disease; metabolic encephalopathies e.g., hepatic, Wilson's).
• Oligodendrocytes: Myelin production (CNS).
  • Injury → demyelination (MS, PML), apoptosis.
  • Inclusions: Glial cytoplasmic inclusions (GCIs) in MSA (α-synuclein).
• Microglia: CNS macrophages (mesodermal).
  • Activation: proliferate, rod cells (neurosyphilis, viral encephalitis).
  • Form microglial nodules (aggregates around injury/inflammation).
  • Phagocytosis → Gitter cells (lipid-laden foamy macrophages).
• Ependymal Cells: Line ventricles & central canal.
  • Reaction: ependymal granulations (subependymal astrocyte proliferation), lining loss.
  • Viral inclusions (e.g., CMV).

⭐ Rosenthal fibers, thick, eosinophilic, irregular structures in astrocytic processes, are characteristic of long-standing gliosis, pilocytic astrocytoma, and Alexander disease.

Cerebral Edema & Herniation - Brain Under Pressure

• Cerebral Edema: Abnormal brain fluid.

  • Types:

    Type	Pathophysiology	Key Feature	Common Causes
    Vasogenic	BBB disruption, ↑ permeability	Extracellular fluid	Tumors, inflammation, trauma, late ischemia
    Cytotoxic	Cellular swelling (Na⁺/K⁺ pump failure)	Intracellular fluid	Ischemia, toxins, hyponatremia
    Interstitial	CSF seepage (obstructive hydrocephalus)	Periventricular WM	Obstructive hydrocephalus
    Osmotic	↓ Plasma osmolality	Global swelling	SIADH, rapid dialysis

  • Clinical: Headache, vomiting, papilledema, altered sensorium.
  • Imaging (CT/MRI): Sulcal effacement, ventricular compression.

• Brain Herniation: Brain displacement from ↑ ICP.

  • Types & Critical Sequelae:

> ⭐ Uncal herniation classically compresses **CN III**, leading to ipsilateral pupillary dilation and oculomotor palsy ('down and out' gaze), and can cause Duret hemorrhages in the brainstem.

High‑Yield Points - ⚡ Biggest Takeaways

• Red neurons: Eosinophilic change, pyknosis; signify acute irreversible neuronal injury (12-24h).
• Central chromatolysis: Axonal reaction; cell body swells, Nissl disperses peripherally.
• Gliosis: CNS scarring; astrocyte hypertrophy/hyperplasia (GFAP+), forms glial scar.
• Rosenthal fibers: Eosinophilic, corkscrew astrocytic processes; seen in pilocytic astrocytoma, Alexander disease.
• Microglial nodules/Neuronophagia: Microglia cluster around dying neurons; common in viral encephalitis.
• Key Inclusions: Negri bodies (rabies), Lewy bodies (Parkinson's), Neurofibrillary tangles (Alzheimer's).