MILD INTRAISCHEMIC HYPOTHERMIA REDUCES POSTISCHEMIC HYPERPERFUSION, DELAYED POSTISCHEMIC HYPOPERFUSION, BLOOD-BRAIN-BARRIER DISRUPTION, BRAIN EDEMA, AND NEURONAL DAMAGE VOLUME AFTER TEMPORARY FOCAL CEREBRAL-ISCHEMIA IN RATS

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 less than or equal to 0.01) and postischemic delayed hypoperfusion (p less than or equal to 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 less than or equal to 0.01). Hypothermia also reduced the volume of both brain edema (p less than or equal to 0.01) and neuronal damage (p less than or equal to 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.