Graded Focal Cerebral Ischemia in the Rat by Unilateral Carotid Artery Occlusion and Elevated Intracranial Pressure: Hemodynamic and Biochemical Characterization

SUMMARY Graded transient cerebral hemispheral ischemia was produced in nitrous oxide-anesthetized Wistar rats by a procedure combining unilateral common carotid artery occlusion; elevation of intracranial pressure to 40-45 mm Hg by infusion of mock cerebrospinal fluid; and maintenance of arterial blood pressure at 100-110 mm Hg by controlled hemorrhage. Cerebral perfusion pressure was thus reduced into the ischemic range ipsilateral to carotid occlusion but remained 55-70 mm Hg contralaterally. Regional cerebral blood flow, measured autoradiographically, fell by 85-90 % in the ischemic dorsolateral and lateral neocortex, hippocampus and lateral striatum, but remained at 71 % of control or higher contralaterally. Metabolite assay revealed a gradient of energy depletion, with profound reductions in ATP and phospho-creatine and marked elevations of lactate in lateral neocortex, lateral striatum, hippocampus and lateral thalamus. Importantly, dorsolateral neocortex proved to be a penumbral zone, with marked lactate eleva-tion comparable to that of lateral cortex, yet only intermediate degress of ATP and PCr reduction. Contralateral structures were metabolically unaffected apart from mild increases in lactate. The advan-tages of this focal ischemia model include the consistent topographic d istribution of ischemia and its regional gradations of intensity; the avoidance of painstaking intracranial microsurgery and of systemic complica-tions; preservation of intact energy state of the contralateral hemisphere; ease of reversibility of ischemia