Huang Ruoyu, Pang Qiuyu, Zheng Lexin, Lin Jiaxi, Li Hanxi, Wan Lingbo, Wang Tao
Department of Forensic Science, School of Basic Medicine and Biological Sciences, Suzhou Medicine College of Soochow University, Suzhou, Jiangsu Province, China.
Neural Regen Res. 2025 Apr 1;20(4):1015-1030. doi: 10.4103/NRR.NRR-D-23-01462. Epub 2024 Apr 3.
Cholesterol is an important component of plasma membranes and participates in many basic life functions, such as the maintenance of cell membrane stability, the synthesis of steroid hormones, and myelination. Cholesterol plays a key role in the establishment and maintenance of the central nervous system. The brain contains 20% of the whole body's cholesterol, 80% of which is located within myelin. A huge number of processes (e.g., the sterol regulatory element-binding protein pathway and liver X receptor pathway) participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis, intracellular transport, and efflux. Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences. Therefore, we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases. Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype, with high mortality and morbidity. Historical cholesterol levels are associated with the risk of intracerebral hemorrhage. Moreover, secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation, such as neuroinflammation, demyelination, and multiple types of programmed cell death. Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage. In this paper, we review normal cholesterol metabolism in the central nervous system, the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage, and the links between cholesterol metabolism and cell death. We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.
胆固醇是质膜的重要组成部分，参与许多基本生命功能，如维持细胞膜稳定性、类固醇激素合成和髓鞘形成。胆固醇在中枢神经系统的建立和维持中起关键作用。大脑含有全身20%的胆固醇，其中80%位于髓鞘内。大量过程（如固醇调节元件结合蛋白途径和肝X受体途径）通过包括胆固醇生物合成、细胞内运输和流出等机制参与大脑中胆固醇代谢的调节。某些涉及上述过程相互作用的脑损伤或疾病会影响正常的胆固醇代谢，从而引发有害后果。因此，我们推测与胆固醇相关的分子和途径可作为中枢神经系统疾病的治疗靶点。脑出血是最严重的出血性卒中亚型，具有高死亡率和高发病率。既往胆固醇水平与脑出血风险相关。此外，脑出血后的继发性病理变化与胆固醇代谢失调有关，如神经炎症、脱髓鞘和多种类型的程序性细胞死亡。脑出血后已发现大脑内细胞内胆固醇蓄积。在本文中，我们综述了中枢神经系统中正常的胆固醇代谢、脑出血后参与胆固醇代谢紊乱的已知机制以及胆固醇代谢与细胞死亡之间的联系。我们还综述了基于胆固醇代谢确定的几个可能且有建设性的治疗靶点，为有兴趣治疗脑出血的人员提供基于胆固醇的观点和参考。
