Lithium attenuates blood–brain barrier damage and brain edema following intracerebral hemorrhage via an endothelial Wnt/β‐catenin signaling‐dependent mechanism in mice

• DOI: 10.1111/cns.13832
• Publication Date: 2022-03-28T07:20:10Z
• Authors: Dengpan Song; Ya‐Bin Ji; Xiao‐Wen Huang; Yin‐Zhong Ma; Cheng Fang; Lin‐Hui Qiu; Xi‐Xi Tan; Yi‐Man Chen; Sheng‐Nan Wang; Junlei Chang; Fuyou Guo
• Keywords: Occludin; Evans Blue; Extravasation

Abstract Background Vasogenic cerebral edema resulting from blood–brain barrier (BBB) damage aggravates the devastating consequences of intracerebral hemorrhage (ICH). Although augmentation endothelial Wnt/β‐catenin signaling substantially alleviates BBB breakdown in animals, no agents based on this mechanism are clinically available. Lithium is a medication used to treat bipolar mood disorders and can upregulate signaling. Methods We evaluated protective effect lithium mouse model collagenase IV‐induced ICH. Furthermore, we assessed dependency mice with deletion Wnt7 coactivator Gpr124 . Results treatment (3 mmol/kg) significantly decreased hematoma volume (11.15 ± 3.89 mm 3 vs. 19.97 3.20 vehicle controls, p = 0.0016) improved neurological outcomes following Importantly, increased integrity, as evidenced by reductions levels brain ( 0.0312), Evans blue leakage 0.0261), blood IgG extravasation 0.0009) into tissue around hematoma. Mechanistically, upregulated activity tight junction proteins (occludin, claudin‐5 ZO‐1). integrity was abolished knockout mice, suggesting that its function mainly dependent Gpr124‐mediated Conclusion Our findings indicate may serve therapeutic candidate for treating