Mechanisms of injury and neuronal response to ischemia
Damage to the nervous system can be direct (toxins, infections) and indirect (ischemia, metabolic shifts). Neurons are extremely sensitive to oxygen and glucose deprivation, but this sensitivity depends on localization.
In ischemia, the microscopic picture changes in stages:
- After 20 minutes: tigrolysis (breakdown of Nissl substance) begins.
- After 12 hours: cells shrink, the cytoplasm becomes bright pink (so-called "red neurons" appear).
- Further: mitochondrial swelling (microvacuolization) and cytolysis occur.
- Outcome: "ghosts" remain in place of dead cells and are phagocytosed by microglia. Pseudolaminar necrosis and gliosis (astrocytic proliferation) develop in the cortex.
Changes following axon transection
If a neuronal process is severed, the changes affect both the cell body itself and the peripheral part of the axon.
In the neuronal soma, the nucleus shifts to the periphery, and the Nissl substance undergoes chromatolysis. The cell either recovers or dies.
The severed part of the axon undergoes Wallerian degeneration (Turck-Waller degeneration): it breaks down into granular eosinophilic clumps. In peripheral nerves, Schwann cells and macrophages clear away the debris, leaving empty sheaths for regeneration. In the CNS, this process is much slower — microglial macrophages may clear the breakdown zone for months.
Specific (pathognomonic) changes
A number of 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 bodies.
- Herpes simplex virus infection (HSV-1): intranuclear Cowdry type A bodies.
Neurotrophic function and denervation syndrome
The nervous system regulates tissue metabolism via trophogens (peptides, hormones, neurotransmitters). They can directly alter target cell metabolism or act on its genetic apparatus.
If innervation is interrupted, denervation syndrome develops. Its most prominent manifestation is neurogenic atrophy of skeletal muscles.
Signs of atrophy:
- The muscle decreases in size and turns brown due to the accumulation of lipofuscin in residual bodies.
- Adipose and connective tissue proliferate.
- Sensitivity to acetylcholine sharply increases (Cannon's law of denervation), and fibrillation twitches appear.
- Apoptosis is activated (mediated by pro-NGF) and an immune rejection reaction against self-tissues occurs.
Intracranial hypertension and brain herniation
Any space-occupying lesions (tumors, abscesses, hematomas) increase intracranial pressure. The severity of the condition depends not only on the size but also on the growth rate of the lesion.
Increased pressure leads to a chain of complications: sulci and the subarachnoid space narrow, ventricles become deformed, and midline structures shift. Ultimately, internal brain herniations develop: subfalcine (herniation of the cingulate gyrus) or transtentorial (displacement of the temporal lobe under the tentorium cerebelli).
Briefly: answers to topical questions
What types of internal brain herniations (displacements) occur in intracranial hypertension?
When intracranial pressure increases and space-occupying processes develop within the cranial cavity, internal brain herniations form. The main types of displacement are:
- Subfalcine brain herniation — herniation of the cingulate gyrus under the free edge of the falx cerebri.
- Transtentorial herniation — herniation of brain tissue from the medial part of the temporal lobe under the free edge of the tentorium cerebelli.
What macroscopic stages does ischemic cerebral infarction go through?
In the first weeks of ischemic infarction, brain volume increases due to edema, and brain herniations form. After 2–3 days, the infarct area appears soft; with a hemorrhagic component, it represents a zone of tissue destruction with areas of hemorrhage. During the organization stage, a glio-mesodermal scar forms, and in large and extensive infarctions, a glio-mesodermal cyst may form after 1–1.5 months or later.
What is the sensitivity of various brain regions (cortex, hippocampus, Purkinje cells, brainstem) to hypoxia?
Sensitivity to hypoxia and ischemia depends on the brain region. Cortical neurons have extremely high sensitivity: irreversible damage occurs as early as 4–5 minutes after blood flow cessation. Brainstem neurons can tolerate ischemia for up to 30 minutes. Hippocampal formations are also extremely sensitive to global hypoxic-ischemic injury. Data on the sensitivity of Purkinje cells are absent in the cited sources.
What pathogenetic types of brain edema exist?
The development of brain edema and swelling is based on water-electrolyte metabolism disorders, increased osmotic pressure, and slowed blood flow. Pathogenetically, two main types are distinguished:
- Vasogenic edema — develops with increased permeability of the microvascular wall and/or elevated filtration pressure.
- Cytotoxic edema — observed in metabolic disorders.
Remember the inclusion bodies: Parkinson — Lewy (PL), Rabies — Babes-Negri (BN), Herpes — Cowdry A (HA), Poliomyelitis — Cowdry B (PB).
Class and exam questions
What are "red neurons"?
These are shrunken neurons with an intensely eosinophilic (bright pink) cytoplasm and a shrunken nucleus, which appear 12 hours after the onset of ischemia.
How does Wallerian degeneration differ in the CNS and PNS?
In the peripheral nervous system, myelin and axon debris are rapidly phagocytosed by Schwann cells, paving the way for regeneration. In the CNS, microglial macrophages perform the clearance, and the process stretches over months and years.
Why does a denervated muscle acquire a brown color?
Due to a disruption of the synthesis and catabolism balance, autolysosomes form within cells. Undigested organelle residues turn into granules of the aging pigment — lipofuscin, which imparts a brown color.
What else to study on this topic
- Transynaptic degeneration and reactive gliosis
- Classification of trophogens and A.D. Speransky's concept
- Morphological manifestation of the immune response during denervation
- Relationship between the growth rate of a space-occupying lesion and the deformation of brain structures
- Detailed pathogenesis of pseudolaminar cortical necrosis
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