CBF Changes Associated with Focal Ischemic Preconditioning in the Spontaneously Hypertensive Rat

Abstract

Experimental stroke models exhibit robust protection after prior preconditioning (PC) insults. This study comprehensively examined cerebral blood flow (CBF) responses to permanent middle cerebral artery (MCA) occlusion in spontaneously hypertensive rats preconditioned by noninjurious transient focal ischemia, using [ 14 C]iodoantipyrine autoradiography at varied occlusion intervals. Preconditioning was produced by 10-min occlusion of the MCA and ipsilateral common carotid artery under halothane anesthesia. These vessels were permanently coagulated 24 h later in naïve, PC, and sham-operated rats. Infarct volumes were determined from hematoxylin-eosin-stained frozen sections after 1 or 3 days. Edema-corrected infarct volume was reduced from 127621 in naïve rats to 101631 and 52628 mm 3 in sham and PC groups, respectively, at 1 day, with similar results at 3 days. All animals exhibited a consistent CBF threshold for infarction (approximately 30 mL/100 g/ min). Tissue volumes below this threshold were identical in naïve and PC groups after 15-min occlusion. However, by 3 h the volume of ischemic cortex decreased in the PC group but remained unchanged in naïve rats, predicting final infarct volumes. Cerebral blood flow recovery was confirmed in brains of individual rats evaluated by repeated laser Doppler perfusion imaging during the same 3-h interval. Modest sham protection correlated with better-maintained global perfusion, detectable also in the contralateral cortex, apparently reflecting the PC effects of prior anesthesia. These results establish that timely reperfusion of penumbra, achieved by synergistic mechanisms, is a primary determinant of PC-induced protection in experimental stroke.

Delayed Tolerance With Repetitive Transient Focal Ischemic Preconditioning in the Mouse

“…In spontaneously hypertensive rats, part of the IPC-induced tolerance has been attributed to improvement in blood flow over a period of several hours of permanent MCAO. 18 In the present model with transient MCAO, the decrease in LDF over lateral cortex in the ischemic core during the test MCAO was similar to that during each IPC occlusion. Although improved blood flow distribution in penumbra by IPC cannot be excluded, differences in intraischemic regional blood flow determined by autoradiography could not be detected during acute occlusion in rats previously conditioned with 3 10-minute bouts of MCAO.…”

Lipopolysaccharide Induces Early Tolerance to Excitotoxicity via Nitric Oxide and cGMP

“…Depth and duration of anesthesia, important variables in studies of PC, 22,23 were closely monitored and kept constant in all experiments. Body temperature has powerful effects on NMDA-mediated brain injury.…”

Neurovascular Protection by Ischemic Tolerance: Role of Nitric Oxide and Reactive Oxygen Species

“…These investigations have established that ischemic tolerance is associated with genetic, biochemical, and neurophysiological changes in neurons and glia that render the brain more resistant to ischemia. However, it has also been observed that tolerance-inducing stimuli improve microvascular perfusion or cerebral blood flow (CBF) in the postischemic brain (Dawson et al, 1999;Furuya et al, 2005;Hoyte et al, 2006;Nakamura et al, 2006;Zhao and Nowak, 2006). Although these studies have suggested that preconditioning protects cerebral blood vessels from the vasoparalysis induced by cerebral ischemia, the effects of preconditioning on cerebrovascular function and the specific contribution of vascular factors to the protection have not been determined.…”