Song Yiming, Liu Xuanhui, Yuan Jiangyuan, Sha Zhuang, Jiang Weiwei, Liu Mingqi, Qian Yu, Gao Chuang, Gong Zhitao, Luo Hongliang, Zhou Xin, Huang Jinhao, Jiang Rongcai, Quan Wei
Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.
The State Key Laboratory of Neurotrauma Repair and Regeneration, Ministry of Education, Tianjin, China.
Front Neurosci. 2022 Aug 22;16:967297. doi: 10.3389/fnins.2022.967297. eCollection 2022.
Intracerebral hemorrhage (ICH) is a fatal disease with high mortality and poor prognosis that triggers multiple severe brain injuries associated with an inflammatory cascade response that cannot be treated with any effective medication. Atorvastatin (ATO) suppresses inflammation, alleviates brain trauma, and eliminates subdural hematoma. Dexamethasone (DXM) also has the capacity to inhibit inflammation. Thus, we combined ATO with low-dose DXM to treat ICH mice to examine whether the combined treatment can inhibit secondary inflammation around the cerebral hemorrhage and decrease overall mortality. Compared to the monotherapy by either ATO or DXM, the combined treatment significantly improves the survivorship of the ICH mice, accelerates their recovery of impaired neurological function, and modulates the circulating cytokines, oxidative products, and apoptosis. Moreover, the benefit of ATO-DXM combination therapy was most pronounced on day 3 after dosing compared to ATO or DXM alone. Thus, early administration of ATO combined with low-dose-DXM promotes better survival of ICH and improves neurological function by reducing neuroinflammation and brain edema in their early phase.
脑出血(ICH)是一种死亡率高、预后差的致命疾病,会引发多种严重脑损伤,并伴有炎症级联反应,目前尚无有效的药物治疗。阿托伐他汀(ATO)可抑制炎症、减轻脑损伤并消除硬膜下血肿。地塞米松(DXM)也具有抑制炎症的能力。因此,我们将ATO与低剂量DXM联合用于治疗ICH小鼠,以研究联合治疗是否能抑制脑出血周围的继发性炎症并降低总体死亡率。与单独使用ATO或DXM进行单一疗法相比,联合治疗显著提高了ICH小鼠的存活率,加速了其受损神经功能的恢复,并调节了循环细胞因子、氧化产物和细胞凋亡。此外,与单独使用ATO或DXM相比,ATO-DXM联合治疗在给药后第3天的益处最为明显。因此,早期给予ATO联合低剂量DXM可促进ICH患者更好地存活,并通过在早期减少神经炎症和脑水肿来改善神经功能。