II. CYTOPATHOLOGY - PATHOLOGICAL CHANGES IN CELL COMPONENTS

A. Neurons

Neurons are more sensitive to injury than other cell types in the CNS. There may be selective vulnerability of groups of neurons to specific types of processes. The following sections illustrate types of neuronal reactions occurring in various disorders.
1. Central chromatolysis (Axonal reaction): When the axon of a neuron is cut or damaged, the axon and its myelin sheath undergo degeneration distal to the lesion (Wallerian degeneration). The sequence of events that takes place in the cell body is known as central chromatolysis or axonal reaction.

a) The cell body swells.

b) The Nissl bodies disperse and move peripherally.

c) The nucleus is displaced peripherally in the cell.

These changes begin within 24-48 hours and reach a peak at about 2 weeks. This sequence of events is an attempt by the neuron to increase protein synthesis and restore the integrity of its axon after injury; in the PNS, axonal regeneration occurs in most cases. Central chromatolysis is most dramatically seen in anterior horn cells after damage to a peripheral nerve.

2. Wallerian Degeneration: degeneration of axons and myelin sheaths distal to a lesion.

3. Ischemic cell change: Neurons are quickly injured by ischemia (regional absence of blood supply). After 6-12 hours morphological changes include acute shrinkage, angularity, and homogeneous eosinophilia of the cytoplasm. The nucleus becomes shriveled, pyknotic and hyperchromatic. These changes are part of the process of cell death. Affected cells are called ischemic neurons or red neurons or eosinophilic neurons.

4. Chronic cell change (simple atrophy): Chronic cell change is generally seen in degenerative conditions of unknown etiology. In chronic cell change the cell body shrinks and becomes more angular; the nucleus becomes pyknotic and hyperchromatic, but the cytoplasm is not eosinophilic as in the ischemic neuron.

5. Inclusions: Intracellular inclusions are mainly found in two types of conditions: viral infections and degenerative diseases.

a) In many cases of viral encephalitis, characteristic inclusion bodies occur in the cytoplasm or nucleus of infected cells. The inclusion bodies are not pathognomonic except in rabies, where Negri bodies occur.

b) In some degenerative diseases, specific types of intraneuronal inclusions characteristically occur. For example, in Parkinson's disease, large spherical intracytoplasmic inclusions called Lewy bodies are found. In Alzheimer's disease, cytoplasmic accumulation of abnormal neurofilaments, called neurofibrillary tangles occurs.

6. Storage in neurons: Neurons may be the site of storage of uncatabolized substances, such as lipids, in a number of inborn errors of metabolism resulting from deficiencies of lysosomal enzymes.
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