Xiao Linglong, Zheng Huaping, Li Jing, Zeng Meiqin, He Dian, Liang Jianhao, Sun Kaijian, Luo Yunhao, Li Feng, Ping Baohong, Yuan Wen, Zhou Hongwei, Wang Qinghua, Sun Haitao
Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
Biomed Pharmacother. 2022 May;149:112797. doi: 10.1016/j.biopha.2022.112797. Epub 2022 Mar 10.
Intracerebral hemorrhage (ICH) has a high mortality and disability rate. Fewer studies focus on white matter injury (WMI) after ICH, especially the corticospinal tract (CST) injury located in the spinal cord, which correlates with motor impairments. Recent studies have shown that gut microbiota dysbiosis occurs after ICH. Furthermore, NLRP3 inflammasome can be activated after ICH, resulting in inflammatory cascade reactions and aggravating brain injury. However, no direct and causal correlation among NLRP3 inflammasome inhibition, altered gut microbiota, and CST injury following ICH has been reported. This study aimed to investigate the effect of MCC950, a selective NLRP3 inflammasome inhibitor, on the gut microbiota and CST injury after ICH. We observed that compared with the sham group, the members of Firmicutes, such as Faecalibaculum and Dubosiella, were depleted in the ICH + Vehicle group, whereas the members of Proteobacteria and Campilobacterota were enriched, such as Enterobacter and Helicobacter. After treatment with MCC950, the Bacteroides, Bifidobacterium and Paenibacillus were relatively abundant in the gut flora of mice. Moreover, we observed CST injury located in cervical enlargement of the spinal cord, and MCC950 alleviated it. Furthermore, treatment with MCC950 decreased the mNSS score and brain water content in ICH. Taken together, the present study showed that MCC950 modulated gut microbiota, effectively attenuated CST injury located in cervical enlargement of the spinal cord, and ameliorated neurological deficits after ICH. This study provided a novel report that links NLRP3 inflammasome inhibition, gut microbiota alteration and CST injury following ICH and profound implications for ICH treatment.
脑出血（ICH）具有较高的死亡率和致残率。较少有研究关注脑出血后的白质损伤（WMI），尤其是位于脊髓的皮质脊髓束（CST）损伤，其与运动障碍相关。最近的研究表明，脑出血后会发生肠道微生物群失调。此外，脑出血后NLRP3炎性小体可被激活，导致炎症级联反应并加重脑损伤。然而，尚未有关于脑出血后NLRP3炎性小体抑制、肠道微生物群改变与CST损伤之间直接因果关系的报道。本研究旨在探讨选择性NLRP3炎性小体抑制剂MCC950对脑出血后肠道微生物群和CST损伤的影响。我们观察到，与假手术组相比，在脑出血+溶剂组中，厚壁菌门的成员，如粪杆菌属和杜氏菌属减少，而变形菌门和弯曲杆菌门的成员，如肠杆菌属和幽门螺杆菌属增加。用MCC950治疗后，小鼠肠道菌群中拟杆菌属、双歧杆菌属和芽孢杆菌属相对丰富。此外，我们观察到脊髓颈膨大处存在CST损伤，而MCC950可减轻这种损伤。此外，用MCC950治疗可降低脑出血小鼠的mNSS评分和脑含水量。综上所述，本研究表明MCC950可调节肠道微生物群，有效减轻脊髓颈膨大处的CST损伤，并改善脑出血后的神经功能缺损。本研究提供了一份新的报告，将脑出血后NLRP3炎性小体抑制、肠道微生物群改变与CST损伤联系起来，并对脑出血治疗具有深远意义。
