The importance of brain temperature in alterations of the blood-brain barrier following cerebral ischemia

Abstract

We studied whether small variations in intraischemic brain temperature influence the response of the blood-brain barrier (BBB) to transient forebrain global ischemia. Six animal subgroups included rats whose brain temperature was maintained at 30, 33, 36 or 39 degrees C during 20 minutes (min) of 4-vessel occlusion. Control rats without ischemia had brain temperature maintained between 30 and 39 degrees C for a 20 min period. After a 45 min postischemic recirculation period, rats were injected with the protein tracer, horseradish peroxidase (HRP), and perfusion fixed 5 or 15 min later. Control rats showed no leakage of the tracer protein. Postischemic rats in which brain temperature was controlled at either 30 or 33 degrees C failed to demonstrate consistent BBB alterations. In contrast, foci of cortical HRP extravasation were consistently documented in rats whose intraischemic brain temperature was 36 degrees C. Permeability alterations were more widespread in the 39 degrees C ischemic group and occurred in cortical, thalamic, hippocampal and striatal regions. The HRP extravasation frequently involved arterioles surrounded by perivascular spaces. Routes of increased permeability to HRP included endothelial pinocytosis, opening of the interendothelial tight junctions and diffuse leakage through damaged endothelial cells. These results demonstrate that brain temperature is a critical factor in determining whether BBB dysfunction is an acute consequence of a transient cerebral ischemic insult.