治疗性电刺激,例如经颅皮层刺激和周围体感刺激,用于改善中风患者的运动功能。我们假设这些刺激通过调节新的共同信号通路在缺血性卒中亚急性期发挥神经保护作用。用高清晰度(HD)-经颅交流电流刺激(tACS;20Hz,89.1A/mm2),HD-经颅直流电刺激(tDCS;强度,55A/mm2;电荷密度,66,000C/m2),或电针(EA,2Hz,1mA)在中风的早期阶段。使用行为运动功能测试评估治疗效果。使用转录组学和其他生物医学分析确定了潜在的机制。所有治疗性电动工具都减轻了缺血性中风引起的运动功能障碍。我们使用转录组分析专注于电刺激参与细胞凋亡和细胞死亡的常见基因,并选择了11个最有效的靶标(Trem2,S100a9,Lgals3,Tlr4,Myd88,NF-kB,STAT1,IL-6,IL-1β,TNF-α,和Iba1)。随后的研究表明,电刺激调节炎症细胞因子,包括IL-1β和TNF-α,通过调节STAT1和NF-kB激活,特别是在变形虫小胶质细胞中;此外,电刺激通过激活神经营养因子增强神经元存活,包括BDNF和FGF9。应用于经颅皮质或外周神经水平以促进功能恢复的治疗性电刺激可以通过调节常见的神经元死亡途径和上调神经营养因子来改善神经保护。因此,联合经颅皮质和外周体感刺激可能发挥协同神经保护作用,进一步增强对缺血性卒中患者运动功能障碍的有益作用。
Therapeutic electrical stimulation, such as transcranial cortical stimulation and peripheral somatosensory stimulation, is used to improve motor function in patients with stroke. We hypothesized that these stimulations exert neuroprotective effects during the subacute phase of ischemic stroke by regulating novel common signaling pathways. Male C57BL/6J mouse models of ischemic stroke were treated with high-definition (HD)-transcranial alternating current stimulation (tACS; 20 Hz, 89.1 A/mm2), HD-transcranial direct current stimulation (tDCS; intensity, 55 A/mm2; charge density, 66,000 C/m2), or electroacupuncture (EA, 2 Hz, 1 mA) in the early stages of stroke. The therapeutic effects were assessed using behavioral motor function tests. The underlying mechanisms were determined using transcriptomic and other biomedical analyses. All therapeutic electrical tools alleviated the motor dysfunction caused by ischemic stroke insults. We focused on electrically stimulating common genes involved in apoptosis and cell death using transcriptome analysis and chose 11 of the most potent targets (Trem2, S100a9, Lgals3, Tlr4, Myd88, NF-kB, STAT1, IL-6, IL-1β, TNF-α, and Iba1). Subsequent investigations revealed that electrical stimulation modulated inflammatory cytokines, including IL-1β and TNF-α, by regulating STAT1 and NF-kB activation, especially in amoeboid microglia; moreover, electrical stimulation enhanced neuronal survival by activating neurotrophic factors, including BDNF and FGF9. Therapeutic electrical stimulation applied to the transcranial cortical- or periphery-nerve level to promote functional recovery may improve neuroprotection by modulating a common neuronal death pathway and upregulating neurotrophic factors. Therefore, combining transcranial cortical and peripheral somatosensory stimulation may exert a synergistic neuroprotective effect, further enhancing the beneficial effects on motor deficits in patients with ischemic stroke.