Electroacupuncture Protects Against Post-stroke Cognitive Impairment by Promoting an IL-33/ST2 Axis-Mediated Microglia M2 Polarization

IF 3.8 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yuhan Zhang, Zhimin Ding, Yamin Wang, Hao Liu, Jing Gao, Huiling Wang, Mingli Wu, Xiaodong Feng, Xin Shen
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引用次数: 0

Abstract

Post-stroke cognitive impairment (PSCI) is a common and debilitating complication of stroke that significantly hinders rehabilitation. Electroacupuncture (EA), which integrates traditional acupuncture with electrical stimulation, has been widely applied in clinical practice and shown remarkable efficacy in treating PSCI. However, its underlying mechanisms remain largely unexplored. The PSCI rat model was established by middle cerebral artery occlusion/reperfusion (MCAO/R). EA treatment commenced 24 h after reperfusion and was administered daily for two weeks. To investigate the role of the Interleukin-33 (IL-33)/Interleukin 1 Receptor-Like 1 (ST2) signaling pathway in EA’s therapeutic effects, the ST2 inhibitor Astegolimab (Anti-ST2) was stereotactically injected into the lateral ventricle prior to EA intervention. Neurological function was evaluated using the Zea-Longa neurological deficit score, while emotional and cognitive behaviors were assessed through the open field test (OFT) and novel object recognition (NOR) test. Cerebral infarct volume was quantified using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Protein expression in the striatum was analyzed by Western blotting and immunofluorescence staining, and structural alterations were examined using hematoxylin–eosin (HE) staining. Microglial polarization in the ischemic penumbra was evaluated via double immunofluorescence staining. Serum levels of inflammatory cytokines, including interleukin (IL)-33, IL-10, IL-4, TNF-α, IL-1β, and IL-6, were determined using enzyme-linked immunosorbent assay (ELISA). EA markedly enhanced learning and memory in stroke rats, upregulated IL-33 expression, promoted M2 microglial polarization, and preserved the integrity of brain white matter. However, blockade of the IL-33/ST2 pathway with Anti-ST2 diminished the therapeutic benefits of EA, aggravated white matter injury and cerebral infarct volume, and amplified the inflammatory response. EA facilitates microglial polarization toward the M2 phenotype via the IL-33/ST2 signaling pathway, strengthens the structural integrity of cerebral white matter, and promotes neurological recovery after ischemic stroke.

电针通过促进IL-33/ST2轴介导的小胶质细胞M2极化来预防脑卒中后认知障碍
脑卒中后认知障碍(PSCI)是一种常见的卒中并发症,严重阻碍康复。电针(Electroacupuncture, EA)是传统针刺与电刺激相结合的疗法,已广泛应用于临床,在治疗PSCI方面疗效显著。然而,其潜在机制在很大程度上仍未被探索。采用大脑中动脉闭塞/再灌注法(MCAO/R)建立PSCI大鼠模型。EA治疗于再灌注后24小时开始,每天给药,持续两周。为了研究白细胞介素-33 (IL-33)/白细胞介素1受体样1 (Interleukin- 1 receptor -样1,ST2)信号通路在EA治疗中的作用,在EA干预前将ST2抑制剂阿斯特戈利单抗(Anti-ST2)立体定向注射到侧脑室。采用Zea-Longa神经功能缺损评分评估神经功能,通过开放场测试(OFT)和新物体识别(NOR)测试评估情绪和认知行为。脑梗死体积采用2,3,5-三苯四唑氯化(TTC)染色定量。Western blotting和免疫荧光染色分析纹状体蛋白表达,苏木精-伊红(HE)染色检测结构变化。双免疫荧光染色评价缺血半暗区小胶质细胞极化。采用酶联免疫吸附法(ELISA)检测血清炎症因子水平,包括白细胞介素(IL)-33、IL-10、IL-4、TNF-α、IL-1β和IL-6。EA显著增强脑卒中大鼠学习记忆能力,上调IL-33表达,促进M2小胶质细胞极化,保持脑白质完整性。然而,用Anti-ST2阻断IL-33/ST2通路会降低EA的治疗效果,加重白质损伤和脑梗死体积,并放大炎症反应。EA通过IL-33/ST2信号通路促进小胶质细胞向M2表型极化,增强脑白质结构完整性,促进缺血性脑卒中后神经功能恢复。
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来源期刊
Neurochemical Research
Neurochemical Research 医学-神经科学
CiteScore
7.70
自引率
2.30%
发文量
320
审稿时长
6 months
期刊介绍: Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.
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