Role of blood-brain barrier permeability in focal ischemic brain edema

We studied how changes in BBB function are related to the development of ischemic brain edema. Focal cerebral ischemia was produced by left MCA occlusion in rats. The permeability of the BB to small or large molecules was evaluated qualitatively by the extravasation of EB or NaFl dyes and quantitatively by the uptake index of 125I-BSA or 14C-sucrose. Brain water content was determined by specific gravity. Measurements were made from the cortical core of the MCA territory within 14 days of occlusion. Water content progressively increased within 2 days of occlusion and then gradually decreased up to 14 days. Lightly stained EB areas were located only in the proximal portion of the ischemic core. The incidence of NaFl extravasation was similar to that of EB within 2 days of occlusion but was greater than that of EB 3 days after occlusion. NaFl staining diffusely extended into the ischemic core. Although the index of 125I-BSA increased only slightly within 2 days of occlusion, a marked increase in 125I-BSA was found after 3 days. The index of 14C-sucrose increased gradually after occlusion, reaching a peak at 8 days. These findings indicate that the change in BBB permeability is minimal in ischemic brain tissue when the accumulation of edema fluid is maximal and suggest that BBB alteration in ischemic brain tissue may be associated with the stabilization or resolution of the ischemic lesion.