Zhang Chenrui, Li Liaoyu, Wang Feng, Du Hailong, Wang Xiaoliang, Gu Xiaoyu, Liu Xinlei, Han Haie, Wu Jianliang, Sun Jianping
Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, China.
Department of Thyroid and Breast Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, China.
Curr Neurovasc Res. 2025;21(4):472-482. doi: 10.2174/0115672026352738241205105129.
Stroke, primarily known as ischemic stroke, is a leading cause of mortality and disability worldwide. Reperfusion after the ischemia stroke resolves is necessary for maintaining the health of brain tissues; however, it also induces inflammation and oxidative stress, resulting in brain injury. This study aimed to investigate the role of circ0001679 in the pathology of I/R (Ischemia/Reperfusion)-induced brain injury and explore its therapeutic potential for I/R injury.
The Oxygen-Glucose Deprivation/Re-oxygenation (OGD/R) model was employed in primary mouse astrocytes, and the Middle Cerebral Artery Occlusion (MCAO) model was established in mice to mimic ischemia-reperfusion-induced injury. Si-circ0001679, anti-miR- 216, and TLR4 ORF-clone were transfected either in cells or mice to study the molecular mechanisms during I/R-induced injury. Inflammation and oxidative stress were monitored after treatment.
Upregulated gene expression of circ0001679 was noticed in both OGD/R-treated primary mouse astrocytes and MCAO-induced mouse brain tissue. Silencing circ0001679 reduced cellular damage, inflammation, and oxidative stress induced by OGD/R treatment. Knocking down of circ0001679 alone with either miR-216 inhibition or TLR4 overexpression increased the inflammation response and oxidative stress compared to circ0001679 silencing only. Moreover, inhibition of circ0001679 attenuated brain injury in MCAO-treated mice via reduced infarction, neuronal damage, apoptosis, inflammation, and oxidative stress.
This study unveiled a novel regulatory axis of circ0001679-miR-216-TLR4 in I/Rinduced brain injury. Targeting circ0001679 may represent a promising therapeutic strategy for I/R-induced brain injury.
中风，主要指缺血性中风，是全球范围内导致死亡和残疾的主要原因。缺血性中风缓解后的再灌注对于维持脑组织的健康是必要的；然而，它也会引发炎症和氧化应激，从而导致脑损伤。本研究旨在探讨circ0001679在缺血/再灌注（I/R）诱导的脑损伤病理过程中的作用，并探索其对I/R损伤的治疗潜力。
在原代小鼠星形胶质细胞中采用氧糖剥夺/复氧（OGD/R）模型，并在小鼠中建立大脑中动脉闭塞（MCAO）模型以模拟缺血再灌注诱导的损伤。将Si-circ0001679、抗miR-216和TLR4开放阅读框克隆转染到细胞或小鼠中，以研究I/R诱导损伤过程中的分子机制。治疗后监测炎症和氧化应激情况。
在OGD/R处理的原代小鼠星形胶质细胞和MCAO诱导的小鼠脑组织中均观察到circ0001679基因表达上调。沉默circ0001679可减少OGD/R处理诱导的细胞损伤、炎症和氧化应激。与仅沉默circ0001679相比，单独敲低circ0001679并抑制miR-216或过表达TLR4会增加炎症反应和氧化应激。此外，抑制circ0001679可减轻MCAO处理小鼠的脑损伤，表现为梗死面积减小、神经元损伤减轻、细胞凋亡减少、炎症减轻和氧化应激减轻。
本研究揭示了I/R诱导的脑损伤中circ0001679-miR-216-TLR4的新型调控轴。靶向circ0001679可能是治疗I/R诱导的脑损伤的一种有前景的治疗策略。
