Objective:Tracer constants (K_i) for blood-to-brain diffusion of sucrose were measured in the rat to profile the time course of blood-brain barrier injury after temporary focal ischemia, and to determine the influence of post-ischemic hypothermia.Methods:Spontaneously hypertensive rats were subjected to transient (2 hours) clip occlusion of the right middle cerebral artery. Reperfusion times ranged from 1.5 min to 46 hours, and i.v. ³H-sucrose was circulated for 30 min prior to each time point (1h, 4h, 22h, and 46h; n=5-7 per time point). K_i was calculated from the ratio of parenchymal tracer uptake and the time-integrated plasma concentration. Additional groups of rats (n=7-8) were maintained either normothermic (37.5^oC) or hypothermic (32.5^oC or 28.5^oC) for the first 6 hours of reperfusion, and K_i was measured at 46 hours.Results:Rats injected after 1.5 - 2 min exhibited a 10-fold increase in K_i for cortical regions supplied by the right middle cerebral artery (p<0.01). This barrier opening had closed within 1 to 4 hours post-reperfusion. By 22 hours, the blood-brain barrier had re-opened, with further opening 22 and 46 hours (p<0.01), resulting in edema. Whole body hypothermia (28^oC-29^oC) during the first six hours of reperfusion prevented opening, reducing K_i by over 50% (p<0.05).Conclusion:Transient middle cerebral artery occlusion evokes a marked biphasic opening of the cortical blood-brain barrier, the second phase of which causes vasogenic edema. Hypothermic treatment reduced infarct volume and the late opening of the blood-brain barrier. This opening of the blood-brain barrier may enhance delivery of low permeability neuroprotective agents.