NEUROPROTECTION WITH NBQX IN RAT FOCAL CEREBRAL-ISCHEMIA - EFFECTS ONADC PROBABILITY-DISTRIBUTION FUNCTIONS AND DIFFUSION-PERFUSION RELATIONSHIPS

Background and Purpose We have previously shown that treatment with gl utamate receptor antagonists after focal ischemia can partially revers e acute lesions measured with diffusion-weighted MRI. The goal of this study was to examine the quantitative nature of these effects of neur oprotection. Methods Rats were subjected to permanent occlusion of the middle cerebral artery under halothane anesthesia and treated with -d ihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) (30 mg/kg IP; two doses given immediately after ischemia and 1 hour after ischemia) or given injections of saline. Diffusion-weighted MRI scans were perfo rmed to map the changes in water diffusivity during the first 3 hours after ischemia. Apparent diffusion coefficients (ADCs) within the isch emic hemisphere were calculated, and ischemic changes were expressed a s absolute reductions and as a percentage of contralateral mean values . Relative perfusion deficits in the ischemic hemisphere were assessed with dynamic MRI of transient changes in transverse relaxation rates (Delta R2). Results Analysis with ADC probability distribution functi ons showed that focal ischemia was present with gradients in ADC reduc tions emanating from the center to the periphery of the lesion. Ischem ic evolution in control rats was manifested as a progressive shift of the probability distribution functions over time. NBQX treatment resul ted in a reverse shift of these probability functions. By 3 hours afte r occlusion, probability distribution functions were significantly imp roved in treated rats (P<.05). Because of the temporal evolution of th e probability distribution functions, ADC thresholds that correlated w ith histological outcomes of infarction changed over time. NBQX did no t alter the cerebral perfusion index, measured as Delta R2 peak value s. Conclusions The results indicate that ADC probability distribution functions can be used to quantitatively evaluate the effects of neurop rotective treatment on the gradients of injury in focal cerebral ische mia. The probability functions also allow for intrasubject comparisons and may therefore be useful for exploring therapeutic windows.