An integrated analysis of the progression of cell responses induced by permanent focal middle cerebral artery occlusion in the rat

Defining the chronology and severity of cell damage in an evolving lesion a fter ischemia is important for understanding the underlying mechanisms in t he development of therapeutic intervention. In the present study, we used a combination of histological and immunocytochemical methods to evaluate cel l responses from 30 min to 48 h after permanent occlusion of the middle cer ebral artery (MCAO) in the rat. Specific immunocytochemical markers clearly revealed acute early responses in neurons (neurofilament protein 200), ast rocytes (glial fibrillary acidic protein), and microglia/macrophages (OX-42 and ED-1) such as enlarged, convoluted neuronal processes, and disintegrat ion of glia. Progressive topographic changes in the developing lesion, pinp ointed by immunolabeling, indicated the severity and extension of the cell damage. Proliferation and hypertrophy of astrocytes and microglia around th e infarct, and contralaterally, occurred 24-48 h after MCAO and coincided w ith mass necrosis and infiltration of neutrophils and macrophages into the core. These observations corroborate the suggestion that the inflammatory p rocess is involved in the progression of the infarct. (C) 1998 Academic Pre ss.