Brain edema and cerebrovascular permeability during cerebral ischemia in rats.

TLDR

Focal cerebral ischemia was induced in 769 rats by left middle cerebral artery occlusion, and blood‑brain barrier permeability was evaluated qualitatively with Evans blue or sodium fluorescein and quantitatively via transfer indexes of I‑125 bovine serum albumin or C‑14 sucrose, while water, sodium, and potassium contents were measured and cortical tissue sampled within 14 days post‑occlusion. Albumin permeability increased within 12 h and remained stable until water content peaked at 3 days, whereas sucrose permeability rose gradually and correlated with water and sodium levels; fluorescein staining was more extensive than Evans blue, and both albumin and sucrose transfer indices surged as edema subsided 4–10 days post‑occlusion, indicating that small‑molecule BBB disruption accompanies edema accumulation and that serum‑protein permeability may aid edema resolution.

Abstract

Focal cerebral ischemia was produced by occluding the left middle cerebral artery in 769 rats. Permeability of the blood-brain barrier to small or large molecules was evaluated qualitatively using Evans blue or sodium fluorescein and quantitatively using the transfer indexes of iodine-125-labeled bovine serum albumin or [14C]sucrose. Water content was determined using wet and dry weights and sodium and potassium contents using flame photometry. Cortical tissue in the middle cerebral artery territory was sampled less than or equal to 14 days after occlusion. A significant increase in the albumin transfer index was first found 12 hours after occlusion, and the index remained approximately the same until water content peaked 3 days after occlusion. In contrast, the sucrose transfer index increased gradually, significantly correlated with increases in the water and sodium contents. Tissue staining by sodium fluorescein was more extensive than that by Evans blue. As edema fluid decreased gradually 4-10 days after occlusion, the albumin and sucrose transfer indexes increased markedly. These findings indicate that disruption of the blood-brain barrier to small molecules is accompanied by accumulation of edema fluid during the later stages of ischemia. Opening of the barrier to serum protein is probably related to the resolution of edema.