BACKGROUND Microglia activation is associated with the development of hypoxic-ischemic brain injury (HIBI). Neuroinflammation suppression might be a suitable therapeutic target in hypoxic oligodendrocyte injury. This study aims to determine whether clemastine can improve hypomyelination by suppressing the activated microglia and promoting the maturation of oligodendrocyte progenitor cells (OPCs) in HIBI. METHODS A bilateral common carotid artery occlusion (BCCAO) rat model that received continuous intraperitoneal injection (1 mg/kg) for 14 days was employed to elaborate the neuroprotection effects of clemastine. Interleukin-1β (IL-1β), nod-like receptor protein 3 (NLRP3), histamine H1 receptor, and OPC differentiation levels in the corpus callosum were measured. Primary cultured OPCs and co-culture of microglia and OPCs were used to explore the link between microglia activation and hypomyelination. Data were evaluated by one-way ANOVA with Fisher's protected least significant difference test. RESULTS Clemastine treatment could reverse hypomyelination and restrain the upregulation of IL-1β and NLRP3 in the corpus callosum of BCCAO rats. Primary cultured OPCs treated with IL-1β showed failed maturation. However, clemastine could also reverse the OPC maturation arrest by activating the extracellular signal-regulated kinase (ERK) signaling pathway. Co-culture of microglia and OPCs with oxygen glucose deprivation treatment exhibited IL-1β and NLRP3 upregulation. Clemastine could downregulate NLRP3 and IL-1β and reverse hypomyelination by inhibiting the p38 signaling pathway. CONCLUSIONS Clemastine could restrain microglia activation, improve axonal hypomyelination in BCCAO rats, and thus might be a viable strategy to inhibit hypomyelination in the corpus callosum of patients with HIBI.

中文翻译：

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卡马斯汀通过减少小胶质细胞来源的IL-1β通过P38信号通路来改善缺氧缺血性脑损伤大鼠的低髓鞘作用。

背景技术小胶质细胞活化与缺氧缺血性脑损伤（HIBI）的发展有关。神经炎症抑制可能是缺氧性少突胶质细胞损伤的合适治疗靶标。这项研究旨在确定clemastine是否可以通过抑制活化的小胶质细胞并促进HIBI中少突胶质细胞祖细胞（OPC）的成熟来改善低髓鞘症。方法采用连续腹膜内注射（1 mg / kg）14天的双侧颈总动脉闭塞（BCCAO）大鼠模型来阐明clemastine的神经保护作用。测量白质中的白介素-1β（IL-1β），结节样受体蛋白3（NLRP3），组胺H1受体和OPC分化水平。使用原代培养的OPC以及小胶质细胞和OPC的共培养物来探索小胶质细胞活化与髓鞘减少之间的联系。数据采用费舍尔保护最小显着差异检验进行单向方差分析。结果卡马斯汀治疗可逆转BCCAO大鼠call体的髓鞘减少，抑制IL-1β和NLRP3的上调。用IL-1β处理的原代培养OPC成熟失败。但是，clemastine也可以通过激活细胞外信号调节激酶（ERK）信号传导途径来逆转OPC成熟阻滞。小胶质细胞和OPCs的共培养与氧葡萄糖剥夺处理显示IL-1β和NLRP3上调。卡马斯汀可以通过抑制p38信号通路来下调NLRP3和IL-1β并逆转低髓鞘。