Lithium Posttreatment Alleviates Blood-Brain Barrier Injury After Intracerebral Hemorrhage in Rats

Vasogenic cerebral edema formation after blood-brain barrier (BBB) damage aggravates the devastating consequences of intracerebral hemorrhage (ICH). The present study aims to probe into a therapeutic method on BBB preservation after ICH with a glycogen synthase kinase-3 beta (GSK-3 beta) inhibitor, lithium. Intrastriatal infusion of semicoagulated autologous whole blood or sham surgery was performed on male Sprague-Dawley (SD) rats (n = 208). Experimental animals received administration of 4,6-disubstitutedpyrrolo-pyrimidine (TWS119), lithium alone or in combination with a phosphatidylinositol 3-kinase inhibitor, wortmannin, after ICH. Behavioral tests, brain edema, and BBB permeability were determined at 24 and 72 h after surgery. Expressions of Akt, GSK-3 beta, beta-catenin, claudin-1 and claudin-3 were evaluated via Western blots. Our results showed lithium alone post-treatment activated GSK-3 beta, therefore increasing active beta-catenin and claudin-1 and claudin-3 expressions, which were accompanied with improved BBB integrity and ameliorated sensorimotor deficits and brain edema in ICH animals. We concluded that lithium alone reduced BBB damage after ICH, likely through regulating AktiGSK-3 beta pathway and stabilizing beta-catenin. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.