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Selective necrosis and total necrosis in focal cerebral ischemia. Neuropathologic observations on experimental middle
Abstract:
Temporary (15 minutes to 24 hours) or permanent focal cerebral ischemia was induced in 87 awake monkeys (Macaca mulatta and Macaca fasicularis) by transorbital snare ligation of the middle cerebral artery (MCA) and neuropathological evaluation was carried out two weeks later. The size, location and histology of lesions varied within each time-period of MCA occlusion. However, most animals that underwent long-term ischemia (eight hours to permanent) had a single, confluent infarct involving deep and sometimes cortical structures. These animals had total necrosis chracterized by: 1. indiscriminate involvement of white and gray matter, 2. relatively sharp margins containing astrocytic and mononuclear cells, 3. an inner zone of liquefaction, infiltrated with fat-laden macrophages and newly formed blood vessels. Animals that underwent moderate to short-term ischemia (30 minutes to four hours) showed multiple, non-confluent deep infarcts. These animals had selective necrosis characterized by: 1. involvement of gray matter and relative sparing of white matter, 2. poorly circumscribed, multiple and often perivascular lesions with incomplete tissue destruction, 3. preferential loss of neurons and proliferation of reactive astrocytes and microglia.
Insights
Middle cerebral artery (MCA) occlusion in monkeys revealed distinct neuropathological changes. Short-term ischemia caused selective gray matter damage, while long-term ischemia resulted in total necrosis affecting both gray and white matter.
Area of Science:
- Neurology
- Neuroscience
- Pathology
Background:
- Focal cerebral ischemia, often caused by middle cerebral artery (MCA) occlusion, is a significant cause of neurological deficits.
- Understanding the neuropathological consequences of varying ischemia durations is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the neuropathological differences between temporary and permanent focal cerebral ischemia in non-human primates.
- To characterize the histological features of lesions resulting from different durations of MCA occlusion.
Main Methods:
- Induction of temporary (15 minutes to 24 hours) or permanent focal cerebral ischemia via transorbital snare ligation of the MCA in 87 awake monkeys (Macaca mulatta and Macaca fasicularis).
- Neuropathological and histological evaluation of brain lesions two weeks after ischemia induction.
Main Results:
- Long-term ischemia (8 hours to permanent) led to single, confluent infarcts with total necrosis, affecting both deep and cortical structures, characterized by indiscriminate white and gray matter involvement and liquefaction.
- Short-term ischemia (30 minutes to 4 hours) resulted in multiple, non-confluent deep infarcts with selective necrosis, primarily involving gray matter with relative sparing of white matter, and perivascular lesions.
Conclusions:
- The duration of MCA occlusion significantly influences the pattern and extent of neuropathological damage in focal cerebral ischemia.
- Distinct histological characteristics differentiate lesions from short-term (selective necrosis) versus long-term (total necrosis) ischemia, providing insights into ischemic brain injury mechanisms.