Escin ameliorates the impairments of neurological function and blood brain barrier by inhibiting systemic inflammation in intracerebral hemorrhagic mice

Abstract

This study aims to investigate whether escin ameliorates the impairments of neurological function by ameliorating systemic inflammation instead of targeting the brain directly in intracerebral hemorrhage (ICH) mice. It showed that escin did not cross the blood brain barrier (BBB). Compared with the ICH group, the Garcia test scores in the escin groups were significantly increased. Brain water contents and Evans blue extravasation of the right basal ganglia in the ICH group were augmented, and significantly reduced by escin. Escin abated the increases of monocyte counts and serum IL-1β levels induced by ICH. IL-1β administration reversed the effect of escin on Garcia test scores, the brain water contents, and the Evans blue extravasation. Escin ameliorated the increasing levels of RhoA, ROCK1, nuclear NF-κB and the decreasing expression of IκBα, cytosolic NF-κB, occludin, claudin-5 in the ICH group. IL-1β administration blocked not only escin-mediated increases of IκBα, cytosolic NF-κB, occludin, and claudin-5, but also escin-caused decreases of RhoA, ROCK1, and nuclear NF-κB. The results indicate that escin improves neurological outcomes and the BBB function in ICH mice, which is associated with attenuating ICH-induced peripheral system inflammation, and therefore, inhibiting IL-1β/RhoA/NF-κB signaling pathway in BBB, at least in part. These findings suggest that it may be useful to ameliorate brain injury by inhibiting systemic inflammation instead of aiming to target the brain directly after ICH.