Department of Chemico-Pharmacological Sciences, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Japan.
Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
J Neuroimmunol. 2019 May 15;330:48-54. doi: 10.1016/j.jneuroim.2019.02.010. Epub 2019 Feb 22.
Inflammatory responses are considered to play pivotal roles in the pathogenesis of intracerebral hemorrhage (ICH). Here we show that a nuclear receptor Nurr1 (NR4A2) was expressed prominently in microglia/macrophages and astrocytes in the perihematomal region in the striatum of mice after ICH. Daily administration of a Nurr1 agonist amodiaquine (40 mg/kg, i.p.) from 3 h after ICH induction diminished perihematomal activation of microglia/macrophages and astrocytes. Amodiaquine also suppressed ICH-induced mRNA expression of IL-1β, CCL2 and CXCL2, and ameliorated motor dysfunction of mice. These results suggest that Nurr1 serves a novel target for ICH therapy.
炎症反应被认为在脑出血 (ICH) 的发病机制中起关键作用。在这里，我们表明，核受体 Nurr1 (NR4A2) 在 ICH 后纹状体血肿周围区域的小胶质细胞/巨噬细胞和星形胶质细胞中表达明显。ICH 诱导后 3 小时开始每天给予 Nurr1 激动剂阿莫地喹（40mg/kg，腹腔注射）可减少血肿周围小胶质细胞/巨噬细胞和星形胶质细胞的激活。阿莫地喹还抑制了 ICH 诱导的 IL-1β、CCL2 和 CXCL2 的 mRNA 表达，并改善了小鼠的运动功能障碍。这些结果表明，Nurr1 是 ICH 治疗的一个新靶点。
