Kv1.3 Blockade Alleviates White Matter Injury through Reshaping M1/M2 Phenotypes via the NF-κB Signaling Pathway after Intracerebral Hemorrhage

作者：Bo Wang, Jie Chen, Shuhong Wang, Lin Chen, Xuyang Zhang, Tengyuan Zhou, Jun Zhong, Chao Zhang, Yijia He, Yonglin Zuo, Hua Feng, Yi Yin, Hongfei Ge · 发表于：Journal of Integrative Neuroscience · 年份：2023 · DOI：10.31083/j.jin2206171 · 被引用次数：11 · 研究领域：Intracerebral and Subarachnoid Hemorrhage Research、Neuroinflammation and Neurodegeneration Mechanisms、Barrier Structure and Function Studies

BACKGROUND: White matter injury (WMI) in basal ganglia usually induces long-term disability post intracerebral hemorrhage (ICH). Kv1.3 is an ion channel expressed in microglia and induces neuroinflammation after ICH. Here, we investigated the functions and roles of Kv1.3 activation-induced inflammatory response in WMI and the Kv1.3 blockade effect on microglia polarization after ICH. METHODS: Mice ICH model was constructed by autologous blood injection. The expression of Kv1.3 was measured using immunoblot, real-time quantitative polymerase chain reaction (RT-qPCR), and immunostaining assays. Then, the effect of administration of 5-(4-Phenoxybutoxy) psoralen (PAP-1), a selectively pharmacological Kv1.3 blocker, was investigated using open field test (OFT) and basso mouse score (BMS). RT-qPCR, immunoblot, and enzyme-linked immunosorbent assay (ELISA) were taken to elucidate the expression of pro-inflammatory or anti-inflammatory factors around hematoma. PAP-1's function in regulating microglia polarization was investigated using immunoblot, RT-qPCR, and immunostaining assays. The downstream PAP-1 signaling pathway was determined by RT-qPCR and immunoblot. RESULTS: Kv1.3 expression was increased in microglia around the hematoma significantly after ICH. PAP-1 markedly improved neurological outcomes and the WMI by reducing pro-inflammatory cytokine accumulation and upregulating anti-inflammatory factors. Mechanistically, PAP-1 reduces NF-κB p65 and p50 activation, thus facilitati...