SEQUENTIAL NEURONAL AND ASTROCYTIC CHANGES AFTER TRANSIENT MIDDLE CEREBRAL-ARTERY OCCLUSION IN THE RAT

The temporal evolution and spatial distribution of ischemic cell injury was investigated after transient middle cerebral artery (MCA) occlusion. Male Wistar rats (n = 61) were subjected to 2 h of MCA occlusion induced by advancing a nylon monofilament into the right internal carotid artery. Animals were killed after different durations of reperfusion, ranging from 4 to 166 h (n = 6-11 for each group). Neuronal injury and astrocytic reaction were evaluated using hematoxylin and eosin (H&E) and glial fibrillary acidic protein (GFAP) immunohistochemistry, respectively. Eosinophilic neurons were detected at 4 h of reperfusion in the basal ganglia, and at 10 h of reperfusion in the cortex. Focal brain infarct developed by 46 h of reperfusion, both in the cortex and the basal ganglia, and the volume remained constant between 46 and 166 h of reperfusion. Significant differences in astrocytic reaction were detected between the lesion and the periphery of the lesion at reperfusion times from 46 to 166 h; GFAP staining decreased in the core of the lesion and increased in the peripheral areas. Our data suggest that, after 2 h of MCA occlusion, brain tissue progresses from isolated neuronal injury to infarct with a time course dependent on anatomical site; and astrocytic reactivity, expressed by GFAP staining, reflects the outcome of the ischemic injury.