Qiu Meiqian, Xu En, Zhan Lixuan
Institute of Neurosciences and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University and Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China.
Front Mol Neurosci. 2021 Oct 11;14:697416. doi: 10.3389/fnmol.2021.697416. eCollection 2021.
Ischemic stroke is one of the leading causes of death and disability worldwide. Microglia/macrophages (MMs)-mediated neuroinflammation contributes significantly to the pathological process of ischemic brain injury. Microglia, serving as resident innate immune cells in the central nervous system, undergo pro-inflammatory phenotype or anti-inflammatory phenotype in response to the microenvironmental changes after cerebral ischemia. Emerging evidence suggests that epigenetics modifications, reversible modifications of the phenotype without changing the DNA sequence, could play a pivotal role in regulation of MM polarization. However, the knowledge of the mechanism of epigenetic regulations of MM polarization after cerebral ischemia is still limited. In this review, we present the recent advances in the mechanisms of epigenetics involved in regulating MM polarization, including histone modification, non-coding RNA, and DNA methylation. In addition, we discuss the potential of epigenetic-mediated MM polarization as diagnostic and therapeutic targets for ischemic stroke. It is valuable to identify the underlying mechanisms between epigenetics and MM polarization, which may provide a promising treatment strategy for neuronal damage after cerebral ischemia.
缺血性中风是全球范围内导致死亡和残疾的主要原因之一。小胶质细胞/巨噬细胞（MMs）介导的神经炎症在缺血性脑损伤的病理过程中起重要作用。小胶质细胞作为中枢神经系统中的固有免疫细胞，在脑缺血后会根据微环境变化转变为促炎表型或抗炎表型。新出现的证据表明，表观遗传修饰，即在不改变DNA序列的情况下对表型进行可逆修饰，可能在MM极化调节中起关键作用。然而，关于脑缺血后MM极化的表观遗传调控机制的了解仍然有限。在这篇综述中，我们介绍了参与调节MM极化的表观遗传机制的最新进展，包括组蛋白修饰、非编码RNA和DNA甲基化。此外，我们讨论了表观遗传介导的MM极化作为缺血性中风诊断和治疗靶点的潜力。确定表观遗传学与MM极化之间的潜在机制很有价值，这可能为脑缺血后神经元损伤提供一种有前景的治疗策略。
