CIMT促进脑缺血大鼠运动功能恢复与局部脑区葡萄糖代谢的相关性

Correlation between recovery of motor function and regional glucose metabolism induced by CIMT in rats with cerebral ischemia

目的研究脑缺血再灌注(middle cerebral artery occlusion,MCAO)模型大鼠在强制性运动疗法(constraint-induced movement therapy,CIMT)干预前后局部脑区葡萄糖代谢水平与行为学评分的相关性,及MCAO模型大鼠自然恢复过程及CIMT干预后的运动恢复情况与脑区激活的相关性,并进一步探讨CIMT的作用机制。方法将22只健康雄性SD大鼠随机分为实验组(6只)、对照组(6只)、假手术组(6只)和正常组(4只)。实验组和对照组通过线栓法建立大鼠MCAO模型,假手术组在手术中不阻断大脑中动脉,正常组不予特殊处理。术后对实验组和假手术组大鼠进行CIMT治疗。在术后第7天和第22天,利用错步实验(foot-fault test,FFT)和平衡木实验(beam balance and walking,BBW)进行前肢运动功能评估;采用微型正电子发射断层扫描仪(micro PET/CT)对大鼠大脑的葡萄糖代谢情况进行扫描;采用皮尔逊相关分析法分别将脑缺血组大鼠的行为学评分与各脑区葡萄糖代谢水平进行相关性分析。结果术后第7天,实验组和对照组大鼠的BBW得分分别与左侧脑区的岛叶皮层、听觉皮层的葡萄糖代谢水平呈负相关,与右侧的脑区后腹部海马、上丘和下丘的葡萄糖代谢水平呈正相关,差异均有统计学意义;错步率分别与左侧脑区的躯体感觉皮层、岛叶皮层和眶额叶皮层的葡萄糖代谢水平呈负相关,与右侧的中脑葡萄糖代谢水平呈正相关,差异均有统计学意义。术后22天,实验组和对照组大鼠的BBW得分分别与左侧脑区的杏仁核、壳尾核、岛叶皮层和内嗅皮层的葡萄糖代谢水平呈正相关,且与右侧脑区的伏隔核和壳尾核的葡萄糖代谢水平呈负相关,差异均有统计学意义;错步率与右侧内嗅皮层呈负相关,差异具有统计学意义。结论CIMT促进大鼠运动功能恢复与双侧大脑半球的激活有关。CIMT促进脑缺血大鼠平衡功能的改善主要与右侧伏隔核的激活有关,其促进大鼠精细抓握功能的恢复可能与右侧内嗅皮层的激活有关。

Objective To study the correlation between regional cerebral glucose metabolism and behavioral scores in middle cerebral artery occlusion(MCAO)model rats before and after the intervention of constraint induced movement therapy(CIMT),and the correlation between the natural recovery process and motor function recovery in MCAO model rats and the brain activation after CIMT intervention,and to further explore the mechanism of CIMT.Methods Twenty-two adult male Sprague-Dawley(SD)rats were randomly divided into an ischemic group treated with CIMT(CIMT,n=6),an ischemic group(Control,n=6),a sham-operated group(Sham,n=6),and a blank control group(Normal,n=4).The MCAO models of rats in the CIMT group and Control group were established by thread embolism method.The middle cerebral artery was not blocked during the operation for the Sham group,and the Normal group was not given any special treatment.After operation,rats in the CIMT group and Sham group were treated with CIMT.On the 7th day(d7)and the 22nd day(d22)after surgery,foot-fault test(FFT)and the beam balance and walking(BBW)test were used to evaluate the forelimb motor;micro positron emission tomography-computed tomography(micro PET/CT)imaging with fluorodeoxyglucose(18F-FDG)was used to scan the glucose metabolism in different brain regions of rats;Pearson correlation analysis was used to analyze the correlation between behavioral scores and glucose metabolism level in the CIMT group and Control group.Results On d7,the BBW score in the CIMT group and Control group was negatively correlated with glucose metabolism in the left insular cortex and the auditory cortex,and positively correlated with glucose metabolism in the right posterior hippocampus,superior colliculus,and inferior colliculus,with statistically significant differences;the FFT score was negatively correlated with glucose metabolism in the left somatosensory cortex,insular cortex and orbitofrontal cortex,and positively correlated with glucose metabolism in the right midbrain,with statistically significant differences.On d22,the BBW score in the CIMT group and Control group was positively correlated with glucose metabolism in the amygdala,caudate putamen,insular cortex and entorhinal cortex,and negatively correlated with glucose metabolism in the nucleus accumbens(Acb)core shell and caudate putamen in the right brain region,with statistically significant differences;the FFT score was negatively correlated with the entorhinal cortex in the right hemisphere and the difference was statistically significant.Conclusion The recovery of motor function promoted by CIMT was associated with the activation of both cerebral hemispheres in rats.The improvement of balance function promoted by CIMT in rats with cerebral ischemia was mainly related to the activation of Acb core shell in the right hemisphere.The recovery of fine grasping function promoted by CIMT may be related to the activation of the right entorhinal cortex.