Mild to moderate hypothermia (30-33 degrees C) reduces brain injury after brief (< 2-h) periods of focal ischemia, but its effectiveness in prolonged temporary ischemia is not fully understood. Thirty-two Sprague-Dawley rats anesthetized with 1.5% isoflurane underwent 3 h of middle cerebral artery occlusion under hypothermic (33 degrees C) or normothermic (37 degrees C) conditions followed by 3 or 21 h of reperfusion under normothermic conditions (n = 8/group). Laser-Doppler estimates of cortical blood flow showed that intraischemic hypothermia reduced both postischemic hyperperfusion (p < or = 0.01) and postischemic delayed hypoperfusion (p < or = 0.01). Hypothermia reduced the extent of blood-brain barrier (BBB) disruption as estimated from the extravasation of Evans blue dye at 6 h after the onset of ischemia (p < or = 0.01). Hypothermia also reduced the volume of both brain edema (p < or = 0.01) and neuronal damage (p < or = 0.01) as estimated from Nissl-stained slides at both 6 and 24 h after the onset of ischemia. These results demonstrate that mild intraischemic hypothermia reduces tissue injury after prolonged temporary ischemia, possibly by attenuating postischemic blood flow disturbances and by reducing vasogenic edema resulting from BBB disruption.