头皮机械刺激通过控制脑水肿减轻2-VO大鼠脑低灌注

Scalp mechanical stimulation alleviates cerebral hypoperfusion in rats with 2-VO by controlling cerebral edema

目的:探讨头皮机械刺激(SMS),作用机理与头针相似,对脑低灌注大鼠脑水肿的脑保护作用。方法:首先,我们通过测量皮肤温度和脑血流量来筛选SMS的强度。接下来,我们观察了头皮机械刺激对2-VO模型大鼠脑血流量、脑水肿和相关病理学改变的脑保护作用。利用免疫组化和免疫印迹法检测神经凋亡相关蛋白(caspase-3、cleaved-caspase-3)和脑水肿相关蛋白(GFAP和AQP4)的表达差异。随后分析神经细胞凋亡与AQP4蛋白水平的相关性。结果:0.5 N为最适合本研究的刺激强度。与对照组相比,0.5 N、1 N、2 N组均可以维持头皮温度,改善脑血流量(均P<0.05)。SMS干预显著增加了2-VO大鼠脑血流量,降低脑含水量(P<0.001和P=0.0449)。与2-VO组相比,SMS组大鼠海马CA1区caspase-3阳性细胞数(P=0.0086)和cleavedcaspase-3阳性细胞数(P=0.036)显著减少,与caspase-3蛋白表达水平(P=0.019)相似。与sham组比较,2-VO组大鼠GFAP和AQP4表达增高(P=0.0369和P=0.0142),SMS组大鼠GFAP和AQP4表达明显降低(P=0.0484和P=0.0229)。AQP4与caspase-3、cleavedcaspase-3的表达呈正相关(R2=0.6071/R2=0.8500)。结论:本研究揭示了SMS改善脑低灌注的最佳强度及其可能的作用机制。SMS可能是一种简便、有前景的预防缺血性卒中和认知障碍的方法。

Objective:To illustrate the cerebral protective effect of scalp mechanical stimulation(SMS),similar to scalp acupuncture in basic mechanism,on cerebral edema in rats with cerebral hypoperfusion.Methods:First,we screened the strength of SMS by measuring skin temperature and blood perfusion using laser speckle contrast imaging.Next,we observed the cerebral protective effects on cerebral blood perfusion,cerebral edema,and pathological changes in rats with modified two-vessel carotid artery occlusion(2-VO).Furthermore,the apoptosis-related proteins(caspase-3,cleaved-caspase-3)and cerebral edema related proteins[antiglial fibrillary acidic protein(GFAP)and antiaquaporin-4(AQP4)]were measured via immunohistochemistry and Western blot analysis.Additionally,the correlation between neural apoptosis and AQP4 protein levels was analyzed.Results:We found that 0.5 N was the best SMS intensity suitable for our study.Compared with the control group,0.5,1,and 2 N maintained the scalp temperature and improved scalp blood flow(all P<.05).SMS intervention significantly increased cerebral blood flow and reduced the brain water content in rats with 2-VO(P<.001 and P=.0449,respectively).Compared to the rats with 2-VO,SMS treatment significantly reduced the number of caspase-3-positive cells(P=.0086)and cleaved caspase-3-positive cells(P=.036)in the hippocampal CA1,which was similar to the protein level of caspase-3(P=.019).Compared to the sham group,the expression of GFAP and AQP4 was higher in the 2-VO group(P=.0369 and P=.0142),which was significantly decreased by SMS(P=.0484 and P=.0229).The expression of AQP4 was positively correlated with the expression of caspase-3 or cleaved caspase-3(R^(2)=0.6071/R^(2)=0.8500).Conclusion:This study demonstrated the optimum SMS intensity for ameliorating cerebral hypoperfusion and its possible mechanism of action.Therefore,SMS is a promising and straightforward method for preventing ischemic stroke and cognitive impairment.