tDCS对中风大鼠功能恢复和Notch信号通路的影响

Effect of transcranial direct current stimulation on Notch pathway activation and functional recovery promotion in stroke rats

临床研究表明,在大鼠双眼眶上孔、眶下缘和鼻交点处采用经颅直流电刺激(transcranial direct current stimulation,tDCS)有助于中风后的康复.然而,tDCS的潜在神经生物学机制仍然知之甚少.本研究主要关注卒中后tDCS疗法对功能恢复和Notch信号通路的影响.采用大鼠中脑动脉闭塞(middle cerebral arterial occlusion,MCAO)再灌注模型,将实验动物随机分为缺血组(MCAO)和缺血后治疗组(MCAO+tDCS),采用神经系统严重程度评分(modified neurological severity score,mNSS)结合动物的行为学表现对神经功能的恢复进行评估.通过2,3,5-三苯基氯化四氮唑(2,3,5-triphenyltetrazole chloride,TTC)染色从组织学上比较治疗前后大鼠脑缺血组织损伤的恢复情况.应用实时定量聚合酶链反应(real time quantitative polymerase chain reaction,RT-PCR)测定缺血性脑中Notch信号通路中受体蛋白、配体蛋白及下游因子的基因表达变化.结果表明,大鼠脑缺血可以激活Notch信号通路,采用多导联脑反射仪的tDCS疗法可以提高Notch信号通路中Notch1、NICD、RBP-JK和Hes-1的mRNA水平,促进神经功能的恢复,并显著减少脑梗死的体积.多导联脑反射仪的tDCS疗法有望发展为一种可靠的临床治疗方式.

Clinical studies show that transcranial direct current stimulation(tDCS)in the intersections of the bilateral supraorbital foramen and inferior orbital rim and nose is helpful for rehabilitation after stroke.However,the neurobiological mechanism of tDCS is poorly understood.Here we focus on the effect of tDCS on functional recovery and Notch signaling pathway after stroke.Middle cerebral arterial occlusion(MCAO)reperfusion is induced in rats.Animals with comparable infarcts are randomly divided into ischemia group(MCAO)and post-ischemia treatment group(MCAO+tDCS).Neural system severity score(mNSS)combined with animal behavioral performance is used to evaluate the recovery of neural function.TTC(2,3,5-triphenyltetrazolium chloride)staining is applied to compare histologically the recovery of ischemic tissue injury before and after treatments.Real-time quantitative polymerase chain reaction(RT-PCR)is used to determine mRNA expression changes of receptor protein,ligand protein,and downstream factor in the Notch signaling pathway in ischemic brains.The results reveal that ischemia could activate Notch signaling pathway,tDCS treated by multilead brain reflex instrument could facilitate mRNA expression of Notch1,NICD,RBP-JK and Hes-1,promote the recovery of neurological function,and significantly reduce the volume of cerebral infarct.Our study suggests that tDCS with multi-lead brain reflex instrument can be expected to become a reliable clinical treatment.