A researcher is studying neuronal changes in various physiologic and pathologic states. Microscopic examination of neural tissue obtained from experimental animals reveals neurons with shrunken nuclei and eosinophilic cytoplasm lacking Nissl bodies. Which of the following is the most likely cause of these findings?
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Neurons are the major functional unit of the nervous system and are characterized histologically by large, round, centrally located nuclei and basophilic cytoplasmic granules composed of rough endoplasmic reticulum (Nissl bodies). When neurons are injured, they undergo distinct histopathologic changes depending on the type of underlying injury.
In response to an acute irreversible injury (eg, severe hypoglycemia, ischemia), neurons begin to display characteristic morphologic changes 12-24 hours after the inciting event, appearing as shrunken cells separated from the surrounding tissue. The nucleus becomes pyknotic (shrunken and basophilic with loss of the nucleolus), and the basophilic Nissl bodies disappear, resulting in cytoplasm that stains deeply eosinophilic (red neurons).
In the brain, in contrast to most other tissues, ischemia ultimately results in liquefactive necrosis due to the breakdown of neural architecture by hydrolytic enzymes released from reacting inflammatory cells and damaged neurons. The necrotic neuronal remnants are then phagocytized by microglia, and astrocytes proliferate at the site of the injury to form a glial scar.
(Choice A) Several neurodegenerative diseases (eg, Alzheimer disease, frontotemporal lobar degeneration) are characterized by intracellular and/or extracellular accumulation of abnormal proteins in neural tissue. Histologic examination of affected areas demonstrates proteinaceous plaques, tangles, and/or inclusions with reactive gliosis and loss of neurons.
(Choice B) Normal aging is associated with progressive atrophy and neuronal loss. However, red neuron changes are not characteristic of age-related physiologic changes.
(Choice C) Lysosomal storage diseases (eg, Tay-Sachs, Niemann-Pick) cause the accumulation of improperly digested substances in lysosomes, leading to neural degeneration through free radical damage and apoptosis. Expected histopathologic changes include enlarged neuronal cells with a foamy appearance due to accumulated undigested macromolecules.
(Choice E) Extensive axon damage or transection results in an axonal reaction characterized by cell body swelling, movement of the nucleus to the periphery, and dispersion of Nissl bodies. This response occurs due to increased protein and lipid synthesis during axon regeneration.
(Choice F) Transient neural compression can lead to a temporary loss of function due to ischemia but would not lead to significant histopathologic changes unless the compression was sustained. Neural compression may occur in the CNS due to increased intracranial pressure or a mass lesion.
Educational objective:
Neurons that sustain irreversible ischemic injury begin to develop characteristic histopathologic changes 12-24 hours after the inciting event. These changes include shrinkage of the cell body, pyknosis of the nucleus, loss of Nissl bodies, and cytoplasmic eosinophilia (red neurons).