Central Nervous System Agents in Medicinal Chemistry

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Postischemic-Anoxic Encephalopathy After Global Forebrain Ischemia

Author(s): Baowan Lin.

Abstract:

Postischemic-anoxic encephalopathy, defined as delayed progressive secondary injury occurs in humans after resuscitation following cardiac arrest. It is much more severe than the initial episode of global brain ischemia from heart attack. This encephalopathy is widespread and may happen after heart surgeries and hypoxia owing to acute carbon monoxide intoxication. About 30%-80% of survivors of resuscitation undergo further brain deterioration, characterized by dementia, Parkinsons syndrome and/or paralysis associated with parenchymal lesions, which may emerge in the days following initial recovery from the acute ischemia. The encephalopathy contains 2 types of injury: 1) macro- and microinfarcts or confluent areas of pan-necrosis with consequent neuronal loss and astroglial activation, 2) perivascular and diffuse tissue sponginess without gliosis. Beta-amyloid protein (Aβ) deposition is found in these patients brains. Experiments reveal that histopathological changes occurring in animals are similar to those in humans. The vicious circle is made of by endothelial injury + platelet aggregation → thrombosis → infarction → endothelial injury and platelet aggregation → thrombosis → circulation decline → infarction. The secondary circulation declines cause the encephalopathy. Endothelial injury and platelet aggregation induce micro- and macro-infarction. Platelet activity and broken bloodbrain barrier (BBB) contribute to part of the Aβ deposition. Cerebral Aβ accumulation induces neuronal shrinkage and disappearance, and may lead to perivascular rarefaction. Cyclooxygenase-2 (COX2) might be involved in the ischemic injury. A combination of protecting endothelia, inhibiting platelet aggregation and activity, and inhibiting COX2 is key to reducing secondary infarction and preventing neurodegeneration, and thus, to alleviate the encephalopathy.

Keywords: encephalopathy, endothelium, platelet, amyloid, degeneration, infarction, ischemia

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Article Details

VOLUME: 8
ISSUE: 3
Year: 2008
Page: [177 - 186]
Pages: 10
DOI: 10.2174/187152408785699631
Price: $58