Early Reperfusion in the Anesthetized Baboon Reduces Brain Damage Following Middle Cerebral Artery Occlusion

Abstract

Background and Purpose Because in humans the clinical benefits of reperfusion remain controversial, it is important to determine whether reperfusion per se reduces infarct volume. In the nonhuman primate, mostly semiquantitative assessments of infarction have been performed. When ischemic volumes have been calculated, it has been for the acute or subacute stages of experimental stroke and may thus not adequately reflect the total volume of consolidated infarction. Methods Anesthetized baboons were subjected to 6 hours of either reversible or permanent middle cerebral artery occlusion (MCAO). Approximately 4 weeks later, the brains were processed for neuropathological examination to allow assessment of the final infarct volume determined by the difference of healthy tissue between occluded and nonoccluded hemispheres. Results Reversible MCAO resulted in a small essentially subcortical infarction (mean±SD, 0.58±0.31 cm 3 ) in 6 of 10 baboons: the infarct (pannecrosis) was restricted to the head of the caudate nucleus, internal capsule, and putamen; 4 of 10 baboons showed no evidence of macroscopic infarction. Permanent MCAO produced a larger subcortical infarct in all 7 baboons studied (2.37±1.32 cm 3 ; P =.0006 by Wilcoxon-Mann-Whitney test); the lesion was more extensive and encompassed the external capsule and, in 2 baboons, the adjacent insular cortex. Conclusions We conclude that under optimal experimental conditions, an ischemic episode of 6 hours in duration is well tolerated in the anesthetized adolescent baboon, with 4 animals showing no signs of macroscopic brain damage. Thus, early reestablishment of cerebral blood flow after a focal ischemic insult is not detrimental but indeed is beneficial in terms of the final infarct volume (both at the subcortical and cortical levels) produced by occlusion of a major cerebral artery. The data further suggest a feasible time window in which to initiate and continue therapeutic interventions.