Injury Mechanisms and Neuronal Response to Ischemia
Nervous system injury can be direct (toxins, infections) or indirect (ischemia, metabolic shifts). Neurons are extremely sensitive to oxygen and glucose deprivation, but this vulnerability depends on their anatomical location.
During ischemia, the microscopic appearance changes sequentially:
- After 20 minutes: Tigrolysis (dissolution of Nissl substance) begins.
- After 12 hours: Cells shrink, the cytoplasm becomes bright pink (forming so-called "red neurons").
- Subsequently: Mitochondrial swelling (microvacuolation) and cytolysis occur.
- Outcome: Ghost cells remain at the sites of dead cells and are phagocytosed by microglia. Pseudolaminar necrosis and gliosis (proliferation of astrocytes) develop in the cortex.
Changes Following Axon Transection
When a neuronal process is transected, changes affect both the cell body and the distal portion of the axon.
In the neuronal soma, the nucleus shifts to the periphery, and Nissl substance undergoes chromatolysis. The cell either recovers or undergoes apoptosis.
The detached distal segment of the axon undergoes Wallerian degeneration: it breaks down into granular eosinophilic debris. In peripheral nerves, Schwann cells and macrophages clear the debris, leaving empty endoneurial tubes for regeneration. In the central nervous system (CNS), this process is much slower—microglial macrophages may clear the disintegration zone for months.
Specific (Pathognomonic) Changes
Certain diseases are characterized by unique intracellular inclusions that serve as precise diagnostic markers:
- Alzheimer's disease: Neurofibrillary tangles.
- Parkinson's disease: Lewy bodies.
- Rabies: Oxyphilic Babes-Negri bodies in the cytoplasm.
- Acute poliomyelitis: Cowdry type B inclusion bodies.
- Herpes simplex virus type 1 (HSV-1) infection: Cowdry type A intranuclear inclusions.
Neurotrophic Function and Denervation Syndrome
The nervous system regulates tissue metabolism using trophogens (peptides, hormones, neurotransmitters). They can alter target cell metabolism directly or influence its genetic apparatus.
When innervation is disrupted, denervation syndrome develops. Its most prominent manifestation is neurogenic skeletal muscle atrophy.
Features of atrophy:
- The muscle shrinks and turns brown due to the accumulation of lipofuscin in residual bodies.
- Adipose and connective tissue proliferate.
- Sensitivity to acetylcholine increases sharply (Cannon's law of denervation), accompanied by fibrillary twitching.
- Apoptosis is activated (mediated by pro-NGF), and an immune rejection reaction against autologous tissues may occur.
Intracranial Hypertension and Brain Herniation
Any space-occupying lesions (tumors, abscesses, hematomas) increase intracranial pressure (ICP). The severity of the condition depends not only on the size of the lesion but also on its growth rate.
Elevated pressure leads to a cascade of complications: sulci and subarachnoid spaces narrow, ventricles are deformed, and midline structures shift. Eventually, internal brain herniations develop: subfalcine herniation (displacement of the cingulate gyrus) or transtentorial herniation (displacement of the temporal lobe beneath the tentorium cerebelli).