3 OPENINGS OF THE BLOOD-BRAIN-BARRIER PRODUCED BY FOREBRAIN ISCHEMIA IN THE RAT

A sensitive radiotracer method was used to explore the time course and regional pattern of blood-brain barrier (BBB) opening that occurs in a rat forebrain ischemia model that mimics temporary cardiac arrest. Immediately following 10 min of ischemia, transfer constants (K(i)) for blood to brain permeation of [H-3]sucrose were augmented severalfold, indicating widespread BBB opening. After 6 h, a delayed intensification of opening was evident in striatum and hippocampus, regions known to undergo selective, delayed neuronal death. There was generalized BBB recovery by 24 h except in experiments that involved prolonged ischemia (25 min) or concomitant brain hyperthermia (41-degrees-C, 10 min). These protocols evoked a third opening; a marked upward increment in K(i) and % H2O developed in neocortex between 6 and 24 h post-ischemia. Pharmacological or other manipulations of these temporal and regional patterns of altered transfer constants may aid understanding of the interplay between microvascular damage, edema, and neuronal death following brain ischemia.