Fu Kaijing, Xu Weilin, Lenahan Cameron, Mo Yong, Wen Jing, Deng Teng, Huang Qianrong, Guo Fangzhou, Mo Ligen, Yan Jun
Department of Neurosurgery, Guangxi Medical University Cancer Hospital, Nanning, China.
Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Front Cell Neurosci. 2023 Jan 16;16:1036313. doi: 10.3389/fncel.2022.1036313. eCollection 2022.
Intracerebral hemorrhage (ICH) is the second-largest stroke subtype and has a high mortality and disability rate. Secondary brain injury (SBI) is delayed after ICH. The main contributors to SBI are inflammation, oxidative stress, and excitotoxicity. Harmful substances from blood and hemolysis, such as hemoglobin, thrombin, and iron, induce SBI. When cells suffer stress, a critical protective mechanism called "autophagy" help to maintain the homeostasis of damaged cells, remove harmful substances or damaged organelles, and recycle them. Autophagy plays a critical role in the pathology of ICH, and its function remains controversial. Several lines of evidence demonstrate a pro-survival role for autophagy in ICH by facilitating the removal of damaged proteins and organelles. However, many studies have found that heme and iron can aggravate SBI by enhancing autophagy. Autophagy and inflammation are essential culprits in the progression of brain injury. It is a fascinating hypothesis that autophagy regulates inflammation in ICH-induced SBI. Autophagy could degrade and clear pro-IL-1β and apoptosis-associated speck-like protein containing a CARD (ASC) to antagonize NLRP3-mediated inflammation. In addition, mitophagy can remove endogenous activators of inflammasomes, such as reactive oxygen species (ROS), inflammatory components, and cytokines, in damaged mitochondria. However, many studies support the idea that autophagy activates microglia and aggravates microglial inflammation the toll-like receptor 4 (TLR4) pathway. In addition, autophagy can promote ICH-induced SBI through inflammasome-dependent NLRP6-mediated inflammation. Moreover, some resident cells in the brain are involved in autophagy in regulating inflammation after ICH. Some compounds or therapeutic targets that regulate inflammation by autophagy may represent promising candidates for the treatment of ICH-induced SBI. In conclusion, the mutual regulation of autophagy and inflammation in ICH is worth exploring. The control of inflammation by autophagy will hopefully prove to be an essential treatment target for ICH.
脑出血（ICH）是第二大常见的中风亚型，具有很高的死亡率和致残率。脑出血后会出现继发性脑损伤（SBI）。继发性脑损伤的主要原因是炎症、氧化应激和兴奋性毒性。血液和溶血产生的有害物质，如血红蛋白、凝血酶和铁，会引发继发性脑损伤。当细胞受到应激时，一种名为“自噬”的关键保护机制有助于维持受损细胞的稳态，清除有害物质或受损细胞器，并使其循环利用。自噬在脑出血的病理过程中起着关键作用，但其功能仍存在争议。有几条证据表明，自噬通过促进受损蛋白质和细胞器的清除，在脑出血中发挥促生存作用。然而，许多研究发现，血红素和铁可通过增强自噬加重继发性脑损伤。自噬和炎症是脑损伤进展的重要元凶。自噬调节脑出血诱导的继发性脑损伤中的炎症，这是一个引人入胜的假说。自噬可以降解并清除前白细胞介素-1β和含半胱天冬酶激活和招募结构域的凋亡相关斑点样蛋白（ASC），以拮抗NLRP3介导的炎症。此外，线粒体自噬可以清除受损线粒体中的炎性小体内源性激活剂，如活性氧（ROS）、炎症成分和细胞因子。然而，许多研究支持自噬激活小胶质细胞并加重小胶质细胞炎症（Toll样受体4（TLR4）途径）这一观点。此外，自噬可通过炎性小体依赖性NLRP6介导的炎症促进脑出血诱导的继发性脑损伤。此外，脑内的一些驻留细胞参与了脑出血后自噬调节炎症的过程。一些通过自噬调节炎症的化合物或治疗靶点可能是治疗脑出血诱导的继发性脑损伤的有希望的候选药物。总之，脑出血中自噬与炎症的相互调节值得探索。通过自噬控制炎症有望成为脑出血的重要治疗靶点。
