INCOMPLETE INFARCT AND DELAYED NEURONAL DEATH AFTER TRANSIENT MIDDLE CEREBRAL-ARTERY OCCLUSION IN RATS

Background and Purpose The clinical syndrome of transient ischemic att acks is accompanied in a significant percentage of patients by brain l esions or neuroimaging abnormalities whose structural counterparts hav e not been defined. The objective of this study was to analyze, in an experimental model of shortterm (<25 minutes) focal ischemia and long- term (less than or equal to 28 days) reperfusion, the extent and natur e of the structural abnormalities affecting neurons and glia located w ithin the territory of the transiently occluded artery. Methods Adult Wistar rats (n=121) had the origin of one middle cerebral artery (MCA) occluded with a nylon monofilament for periods of 10 to 25 minutes. E xperiments of transient MCA occlusion were terminated at variable peri ods ranging from 1 day to 4 weeks. Control experiments consisted of (1 ) MCA occlusion without reperfusion (n=7) lasting 7 to 14 days and (2) sham operations (n=2) followed by 1- to 4-day survival. After in situ fixation, brain specimens were serially sectioned and subjected to de tailed morphometric evaluations utilizing light and electron microscop es. The statistical method used to evaluate the results was based on A NOVA followed by Bonferroni's corrected t test and Student's t test co mparisons. Results Brain lesions were not detectable in the sham-opera ted controls. All brains with permanent MCA occlusion (7 to 14 days) h ad large infarctions with abundant macrophage infiltration and early c avitation. Forty-five (37%) of the experiments involving transient MCA occlusion had no detectable brain lesions after 4 weeks. Selective ne uronal necrosis was found in 76 of 121 rats (63%) with transient MCA o cclusion. Neuronal necrosis always involved the striatum, and in 29% o f the brains with ischemic injury, necrosis also included a short segm ent of the cortex. In the striatum, the length of the arterial occlusi on was the main determinant of the number of necrotic neurons (20 minu tes [22.6+/-19] is worse than 10 minutes [4.9+/-7]) (P<.0001). In the cortex, the length of reperfusion determined the number of necrotic ne urons appearing in layer 3. Experiments with reperfusion of 4 to 7 day s' duration yielded more necrotic neurons per microscopic field (2.02/-3) than those lasting fewer days (0.04+/-0.1) (P<.05). The histologi cal features of these lesions underwent continuous change until the en d of the fourth week, at which time necrotic neurons were still visibl e both in the striatum and in the cortex. Conclusions Arterial occlusi ons of short duration (<25 minutes) produced, in 76 of 121 experiments (63%), brain lesions characterized by selective neuronal necrosis and various glial responses (or incomplete infarction). This lesion is en tirely different from the pannecrosis/cavitation typical of an infarct ion that appears 3 to 4 days after a prolonged arterial occlusion. Del ayed neuronal necrosis, secondary to a transient arterial occlusion or increasing numbers of necrotic neurons in experiments with variable p eriods of reperfusion, was a response observed only at a predictable s egment of the frontoparietal cortex.