(Stroke. 1995;26:636-643.)
© 1995 American Heart Association, Inc.
Articles |
Neuronal Necrosis After Middle Cerebral Artery Occlusion in Wistar Rats Progresses at Different Time Intervals in the Caudoputamen and the Cortex
Presented at the 19th International Joint Conference on Stroke and Cerebral Circulation, San Diego, Calif, February 17-19, 1994, and published in abstract form in Stroke 1994;25:260.
From the Department of Pathology (Neuropathology), Henry Ford Hospital, Detroit, Mich (J.H.G., K.-F.L.), and Case Western Reserve University, Cleveland, Ohio (J.H.G., K.-L.H.).
Correspondence to Dr Julio H. Garcia, Department of Pathology (Neuropathology), Henry Ford Hospital, K-6, 2799 W Grand Blvd, Detroit, MI 48202-2689.
Background and Purpose Most brain lesions that develop after an artery is occluded evolve from an initial stage of "ischemic injury" (probably reversible) to an infarct or an area where most neurons become necrotic. 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 topographic distribution of the neuronal necrosis that follows the occlusion of a large cerebral artery.
Methods One hundred fifty-one adult rats (including 15 controls) were used in this study. One hundred forty-seven had the right middle cerebral artery occluded for variable periods ranging from 30 minutes to 7 days. After processing the brains for histology, a meticulous structural evaluation of each specimen, including quantitation of necrotic neurons, was followed by a detailed statistical analysis of the neuronal counts.
Results Few neurons in isolated sites showed morphological signs of necrosis during the initial 4 hours; the first significant increase in the percentage of necrotic neurons (15%) was observed within the territory of the occluded artery after 6 hours (P<.05); 12 hours after the arterial occlusion most neurons (65%) had become necrotic (P<.0001). Pannecrosis involving neurons, glial cells, and blood vessels was observed at 72 to 96 hours. However, even at this time pannecrosis involved only the preoptic area and the lateral putamen; a few intact neurons remained visible in the cortex, and scattered necrotic neurons could be identified beyond the edges of the "area of pallor," which does not become clearly demarcated until 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 the caudoputamen and then spread to the cortex. The causes for the progression of the lesion are not known; however, therapeutic interventions that start within the first 1 to 2 hours after the arterial occlusion may alter the histopathologic responses to this form of injury. It remains to be determined whether the extent of the neurological deficit induced by an arterial occlusion correlates with the number of necrotic neurons.
Key Words: cerebral ischemia • coagulation • neuronal death • occlusion
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