NEURONAL NECROSIS AFTER MIDDLE CEREBRAL-ARTERY OCCLUSION IN WISTAR RATS PROGRESSES AT DIFFERENT TIME INTERVALS IN THE CAUDOPUTAMEN AND THE CORTEX

Background and Purpose Most brain lesions that develop after an artery is occluded evolve from an initial stage of ''ischemic injury'' (prob ably reversible) to an infarct or an area where most neurons become ne crotic. There is scant information on the time that must elapse after the arterial occlusion for neurons to undergo irreversible injury. The objective of these experiments was to chart the time course and the t opographic distribution of the neuronal necrosis that follows the occl usion of a large cerebral artery. Methods One hundred fifty-one adult rats (including 15 controls) were used in this study. One hundred fort y-seven had the right middle cerebral artery occluded for variable per iods ranging from 30 minutes to 7 days. After processing the brains fo r histology, a meticulous structural evaluation of each specimen, incl uding quantitation of necrotic neurons, was followed by a detailed sta tistical analysis of the neuronal counts. Results Few neurons in isola ted sites showed morphological signs of necrosis during the initial 4 hours; the first significant increase in the percentage of necrotic ne urons (15%) was observed within the territory of the occluded artery a fter 6 hours (P<.05); 12 hours after the arterial occlusion most neuro ns (65%) had become necrotic (P<.0001). Pannecrosis involving neurons, glial cells, and blood vessels was observed at 72 to 96 hours. Howeve r, even at this time pannecrosis involved only the preoptic area and t he lateral putamen; a few intact neurons remained visible in the corte x, and scattered necrotic neurons could be identified beyond the edges of the ''area of pallor,'' which does not become clearly demarcated u ntil 4 to 5 days after the arterial occlusion. Conclusions There is a predictable progression in the development of neuronal necrosis after a permanent arterial occlusion. Irreversible changes appear first in t he caudoputamen and then spread to the cortex. The causes for the prog ression of the lesion are not known; however, therapeutic intervention s that start within the first 1 to 2 hours after the arterial occlusio n may alter the histopathologic responses to this form of injury. It r emains to be determined whether the extent of the neurological deficit induced by an arterial occlusion correlates with the number of necrot ic neurons.