PERI-INFARCT FLOW TRANSIENTS PREDICT OUTCOME IN RAT FOCAL BRAIN ISCHEMIA

Spreading depolarizations are accompanied by transient changes in cerebral blood flow (CBF). In a post hoc analysis of previously studied control rats we analyzed CBF time courses after middle cerebral artery occlusion in the rat in order to test whether intra-ischemic flow, reperfusion, and different parameters of pen-infarct flow transients (PIFTs) (amplitude, number) can predict outcome. Sprague-Dawley rats anesthetized with either halothane (n = 23) or isoflurane (n = 32) underwent 90-min filament occlusion of the middle cerebral artery followed by 72 h of reperfusion. The infarct size was determined by 2,3,5-triphenyltetrazolium chloride staining. Relative CBF changes were monitored by laser Doppler flowmetry at 4-5 mm lateral, and 1-2 mm posterior to Bregma. An additional filament occlusion study (n = 12) was performed to validate that PIFTs were coupled to direct current shifts of spreading depolarization. The PIFT-direct current shift study revealed that every PIFT was associated with a negative direct current shift typical of spreading depolarization. Post-hoc analysis showed that the number of PIFTs, especially with the combination of intra-ischemic level of flow, can predict the development of cortical infarcts. These findings show that PIFTs can serve as an early biomarker in predicting outcome in preclinical animal studies. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.