Huang Jiapeng, Bao Chuncha, Yang Chunlan, Qu Yun
Clinical Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, China.
Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
Mol Neurobiol. 2025 Apr;62(4):4484-4498. doi: 10.1007/s12035-024-04574-x. Epub 2024 Oct 26.
Ischemic stroke is one of the leading causes of death and disability. Dual transcranial direct current stimulation (dual-tDCS) is a promising intervention to treat ischemic stroke, but its efficacy and underlying mechanism remain to be verified. Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has recently emerged as a key mediator in cerebral injury. However, little is known about the effect of cGAS-STING on neuronal damage in ischemic stroke, and it remains to be studied whether the cGAS-STING pathway is involved in tDCS intervention for ischemic stroke. Therefore, we aimed to investigate whether dual-tDCS can alleviate ischemic brain injury in a rat model of ischemic stroke and if so, whether via cGAS-STING pathway. Middle cerebral artery occlusion (MCAO) was employed to induce a rat model of ischemic stroke. Male SD rats weighing 250-280 g were randomly assigned to the Sham, MCAO, Dual-tDCS, Dual-tDCS + RU.521, and Dual-tDCS + 2'3'-cGAMP groups, with 10 rats in each group completing the experiment. Behavioral, morphological, MRI, and molecular biological methods were performed. We found that the cGAS-STING pathway was activated and expressed in neurons after MCAO. Dual-tDCS improved motor function and infarct volume, inhibited neuronal apoptosis, promoted the expression of neurotrophins (BDNF and NGF), CD31, and VEGF, and suppressed inflammation reaction after MCAO via the cGAS-STING pathway. Taken together, dual-tDCS may improve MCAO-induced brain injury and promote the recovery of motor function, resulting from the inhibition of neuronal apoptosis and inflammation reaction, as well as promotion of the expression of nerve plasticity- and angiogenesis-related proteins, via cGAS-STING pathway.
缺血性中风是导致死亡和残疾的主要原因之一。双经颅直流电刺激（dual-tDCS）是一种有前景的治疗缺血性中风的干预方法，但其疗效和潜在机制仍有待验证。环磷酸鸟苷-腺苷合成酶（cGAS）-干扰素基因刺激因子（STING）通路最近已成为脑损伤的关键介质。然而，关于cGAS-STING对缺血性中风中神经元损伤的影响知之甚少，cGAS-STING通路是否参与tDCS对缺血性中风的干预仍有待研究。因此，我们旨在研究双经颅直流电刺激是否能减轻缺血性中风大鼠模型的缺血性脑损伤，如果是，是否通过cGAS-STING通路。采用大脑中动脉闭塞（MCAO）法诱导大鼠缺血性中风模型。将体重250-280g的雄性SD大鼠随机分为假手术组、MCAO组、双经颅直流电刺激组、双经颅直流电刺激+RU.521组和双经颅直流电刺激+2'3'-cGAMP组，每组10只大鼠完成实验。采用行为学、形态学、MRI和分子生物学方法。我们发现MCAO后cGAS-STING通路在神经元中被激活并表达。双经颅直流电刺激通过cGAS-STING通路改善运动功能和梗死体积，抑制神经元凋亡，促进神经营养因子（BDNF和NGF）、CD31和VEGF的表达，并抑制MCAO后的炎症反应。综上所述，双经颅直流电刺激可能通过cGAS-STING通路抑制神经元凋亡和炎症反应，促进神经可塑性和血管生成相关蛋白的表达，从而改善MCAO诱导的脑损伤并促进运动功能恢复。
