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

Neuroscience
Weishan LiXiaobo Tang

Abstract

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-3β (GSK-3β) 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-3β, β-catenin, claudin-1 and claudin-3 were evaluated via Western blots. Our results showed lithium alone posttreatment activated GSK-3β, therefore increasing active β-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 Akt/GSK-3β pathway and stabilizing β-catenin.

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Citations

Oct 20, 2020·Frontiers in Physiology·Romain MenetAyman ElAli
Feb 8, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Huilong LuoXavier Declèves
Jan 18, 2020·Translational Research : the Journal of Laboratory and Clinical Medicine·Mingxi LiHua Feng
Nov 14, 2020·International Journal of Stroke : Official Journal of the International Stroke Society·Siobhan CrillyPaul R Kasher
Jun 9, 2021·Neural Regeneration Research·Yuan ZhuGuo-Hui Jiang

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