Huang Yimin, Li Qing, Tian Hao, Yao Xiaolong, Bakina Olga, Zhang Huaqiu, Lei Ting, Hu Feng
Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology Wuhan 430030, Hubei, P. R. China.
Max Delbrueck Center for Molecular Medicine in The Helmholtz Association Berlin 13125, Germany.
Am J Transl Res. 2020 Oct 15;12(10):6351-6365. eCollection 2020.
Microglia-mediated neuroinflammation is one of the hallmark pathological features following traumatic brain injury (TBI) that contributes to aggravated brain damage and cognitive deficits. These pathologies require novel effective treatments to improve prognosis. Trametinib, a mitogen-activated protein kinase inhibitor approved by the Food and Drug Administration in treating various malignant tumors, has been shown to exert anti-inflammatory effects. The present study demonstrated that TBI mice treated with trametinib exhibited improved cognitive function. Trametinib treatment rescued oligodendrocytes and decreased infiltrating microglial density in the TBI area. Furthermore, this study revealed that ameliorated lipopolysaccharides (LPS) induced inflammatory reaction in microglial cells. Besides, trametinib attenuated inflammation factors expression during the early stages of TBI. In addition, trametinib inhibited LPS-induced microglial chemotactic activity. In conclusion, the results indicate that trametinib efficiently suppresses microglia-induced neuroinflammation and improves cognitive function of TBI mice, providing a potential therapy strategy for TBI patients.
小胶质细胞介导的神经炎症是创伤性脑损伤（TBI）后的标志性病理特征之一，它会导致脑损伤加重和认知缺陷。这些病症需要新的有效治疗方法来改善预后。曲美替尼是一种经美国食品药品监督管理局批准用于治疗各种恶性肿瘤的丝裂原活化蛋白激酶抑制剂，已被证明具有抗炎作用。本研究表明，用曲美替尼治疗的TBI小鼠认知功能得到改善。曲美替尼治疗挽救了少突胶质细胞，并降低了TBI区域浸润的小胶质细胞密度。此外，本研究还表明，曲美替尼改善了脂多糖（LPS）诱导的小胶质细胞炎症反应。此外，曲美替尼在TBI早期减弱了炎症因子的表达。此外，曲美替尼抑制了LPS诱导的小胶质细胞趋化活性。总之，结果表明曲美替尼能有效抑制小胶质细胞诱导的神经炎症并改善TBI小鼠的认知功能，为TBI患者提供了一种潜在的治疗策略。
