OBJECTIVE In ischemic stroke, the ischemic crisis activates a cascade of events that are potentiated by reperfusion, eventually leading to cell death. The chief aim in this study was to investigate whether our new experimental model for stroke therapy, flushing the ischemic territory with saline before reperfusion, could minimize this damage by (1) reducing the inflammatory reaction and (2) improving regional microcirculation. METHODS Stroke in Sprague-Dawley rats (n=39) was induced by a 2-hour middle cerebral artery occlusion with the use of a novel intraluminal hollow filament. Before 48-hour reperfusion, 20 of the ischemic rats received 7 mL isotonic saline at 23 degrees C or 37 degrees C infused into the ischemic area through the filament. Regional cerebral blood flow in cortex supplied by the right middle cerebral artery was measured by laser-Doppler flowmetry during ischemia and reperfusion. Leukocyte infiltration, microvascular plugging, and infarct volume were compared with the use of hematoxylin and eosin staining. Expression of intercellular adhesion molecule 1 (ICAM-1) was determined by immunocytochemistry. Neurological deficits were evaluated. RESULTS After the prereperfusion infusion of saline, significantly (P<0.001) improved cerebral blood flow (105+/-12% of baseline) was obtained up to 48 hours after reperfusion, compared with 45+/-7% at 24 hours and 25+/-3% at 48 hours after reperfusion without local saline infusion. Significant (P<0.001) reductions in leukocyte infiltration (61%), vascular plugging (45%), infarct volume (approximately 65%), and neurological deficits were also produced. ICAM-1 expression in the infarct region was significantly (P<0.05) minimized by 37%. CONCLUSIONS The reduced brain infarct and neurological deficits may be attributed to adequate reperfusion and ameliorated inflammation induced by local prereperfusion infusion.