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脑出血后白质损伤分子机制和治疗研究进展

王晓刚¹, 卢雅彬¹, 李纤^1,2,*

¹首都医科大学基础医学院生物化学与分子生物学学系，北京 100069；²北京市肿瘤转移与侵袭重点实验室，北京市神经损伤与修复重点实验室，北京 100069

摘要

脑出血(intracerebral hemorrhage, ICH)是临床上常见的卒中类型，具有高致残率、高死亡率特点。由于高血压合并细小动脉硬化、血液病或脑血管淀粉样变等病因，血液自破裂的血管溢出，血肿压迫且大量毒性代谢产物可直接损伤脑实质，造成中枢神经系统功能缺陷。中枢神经系统包括灰质与白质，灰质由神经元胞体和树突组成，白质由髓鞘包覆的神经轴突和少突胶质细胞组成。目前，ICH的研究多集中于灰质损伤的机制，而针对白质损伤(white matter injury, WMI)的研究仍处于起步阶段，这或是临床使用神经元退行性变保护剂治疗失败的原因之一。近年来，研究人员已确定占位效应、神经炎症、氧化应激等病理生理机制是ICH后WMI的原因，但其分子机制尚未阐明，故针对ICH后WMI的治疗手段亦不成熟。在本文中，我们将简述白质的结构与功能，总结WMI的病理改变，并重点讨论ICH后WMI的分子机制和治疗研究进展。

关键词： 脑出血; 白质损伤; 分子机制; 治疗手段

Advances in molecular mechanisms and therapeutic strategies of white matter injury after intracerebral hemorrhage 

WANG Xiao-Gang¹, LU Ya-Bin¹, LI Qian^1,2,*

¹Department of Molecular Biology and Biochemistry, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China；²Beijing Key Laboratory of Cancer & Metastasis Research; Beijing Key Laboratory of Neural Regeneration and Repair, Beijing 100069, China

Abstract

Intracerebral hemorrhage (ICH) is the most common subtype of stroke with high disability and high mortality rates. Due to the hypertension with arteriosclerosis, hemopathy and cerebrovascular amyloidosis, the influx of blood from ruptured vessels into the brain destroys the cerebral parenchyma and results in dysfunction of central nervous system because of hematoma compression and a series of toxic metabolites. The cerebral parenchyma consists of gray and white matter. The white matter consists of myelinated axons and oligodendrocytes, whereas the gray matter consists of neuronal cell bodies and dendrites. Currently, most of studies have explored the mechanisms of gray matter injury. But researches of white matter injury (WMI) are still in their infancy, which may be partially responsible for the failure of treatments with neuroprotectants targeting degenerating neuronal cells. In recent years, researchers have progressively identified pathophysiological mechanisms of WMI after ICH including mass effect, neuroinflammation and oxidative stress, but information on the molecular mechanisms of WMI and its effective treatment remains limited. In this paper, we will describe the structure and function of white matter, summarize pathology of WMI and focus on the research advances in the molecular mechanisms and therapeutic strategies of WMI after ICH. 

Key words: intracerebral hemorrhage; white matter injury; molecular mechanisms; therapeutic strategies

收稿日期：　　录用日期：

通讯作者：李纤　　E-mail: qianli@ccmu.edu.cn

DOI: 10.13294/j.aps.2024.0002

引用本文：

王晓刚, 卢雅彬, 李纤. 脑出血后白质损伤分子机制和治疗研究进展[J]. 生理学报 2024; 76 (1): 59-76.

WANG Xiao-Gang, LU Ya-Bin, LI Qian. Advances in molecular mechanisms and therapeutic strategies of white matter injury after intracerebral hemorrhage . Acta Physiol Sin 2024; 76 (1): 59-76 (in Chinese with English abstract).