Department of Neurological Surgery, University of Wisconsin, Madison, Wisconsin, USA.
William S. Middleton Veterans Hospital, Madison, Wisconsin, USA.
J Neurochem. 2024 Oct;168(10):3430-3448. doi: 10.1111/jnc.16055. Epub 2024 Jan 26.
Post-stroke neuroinflammation is pivotal in brain repair, yet persistent inflammation can aggravate ischemic brain damage and hamper recovery. Following stroke, specific molecules released from brain cells attract and activate central and peripheral immune cells. These immune cells subsequently release diverse inflammatory molecules within the ischemic brain, initiating a sequence of events, including activation of transcription factors in different brain cell types that modulate gene expression and influence outcomes; the interactive action of various noncoding RNAs (ncRNAs) to regulate multiple biological processes including inflammation, epitranscriptomic RNA modification that controls RNA processing, stability, and translation; and epigenetic changes including DNA methylation, hydroxymethylation, and histone modifications crucial in managing the genic response to stroke. Interactions among these events further affect post-stroke inflammation and shape the depth of ischemic brain damage and functional outcomes. We highlighted these aspects of neuroinflammation in this review and postulate that deciphering these mechanisms is pivotal for identifying therapeutic targets to alleviate post-stroke dysfunction and enhance recovery.
卒中后的神经炎症在脑修复中起着关键作用，但持续的炎症会加重缺血性脑损伤并阻碍恢复。卒中后，脑细胞释放的特定分子吸引并激活中枢和外周免疫细胞。这些免疫细胞随后在缺血性脑内释放多种炎症分子，引发一系列事件，包括不同脑内细胞类型的转录因子激活，调节基因表达并影响结果；各种非编码 RNA(ncRNA) 的相互作用调节包括炎症在内的多种生物学过程，表观转录组 RNA 修饰控制 RNA 加工、稳定性和翻译；以及在管理对卒中的基因反应中至关重要的表观遗传变化，包括 DNA 甲基化、羟甲基化和组蛋白修饰。这些事件之间的相互作用进一步影响卒中后的炎症，并影响缺血性脑损伤的深度和功能结果。我们在这篇综述中强调了神经炎症的这些方面，并假设破译这些机制对于确定治疗靶点以减轻卒中后功能障碍和促进恢复至关重要。
