基于磁共振波谱成像技术探讨强制性运动疗法对脑缺血再灌注损伤大鼠运动功能的影响

Effect of Constraint-Induced Movement Therapy on Motor Function of Rats with Cerebral Ischemia-Reperfusion Injury Based on Magnetic Resonance Spectroscopy Imaging

目的:基于动物磁共振波谱(MRS)成像技术探讨强制性运动疗法(CIMT)改善脑缺血再灌注损伤大鼠运动功能的机制。方法:采用改良Longa线栓法构建左侧大脑中动脉阻塞(MCAO)再灌注损伤大鼠模型,造模成功后采用随机数字表法分为对照组和CIMT组,每组6只。对照组于笼中自由活动;CIMT组于造模后第7天进行CIMT干预,干预时将大鼠健侧固定后置于跑台上,强迫患侧运动,1次/d,20 min/次,7 d/周,连续干预2周。于干预前后,采用旷场实验评价2组大鼠的运动功能;采用改良神经功能缺损评分(mNSS)评价大鼠神经功能缺损情况;采用9.4 T小动物核磁进行MRS成像扫描,检测大鼠双侧运动皮层M1区谷氨酸和γ-氨基丁酸水平的变化。结果:①运动功能:与对照组比较,CIMT组干预后大鼠自主活动总距离明显增加,差异具有统计学意义(P<0.05)。②神经功能缺损情况:与对照组比较,CIMT组干预后mNSS评分明显降低,差异具有统计学意义(P<0.05)。③运动皮层M1区谷氨酸和γ-氨基丁酸水平比较:与干预前比较,对照组干预后健侧运动皮层M1区谷氨酸/肌酐明显降低,CIMT组干预后患侧运动皮层M1区谷氨酸/肌酐明显升高、γ-氨基丁酸/肌酐明显降低(P<0.05)。与对照组比较,CIMT组干预后患侧运动皮层M1区谷氨酸/肌酐明显升高、γ-氨基丁酸/肌酐明显降低(P<0.05)。结论:强制性运动疗法可改善脑缺血再灌注损伤大鼠的运动功能障碍及神经功能缺损,其机制可能与提高脑缺血再灌注损伤大鼠患侧运动皮层M1区兴奋性神经递质谷氨酸水平,降低抑制性神经递质γ-氨基丁酸水平有关。

Objective:Animal magnetic resonance spectroscopy(MRS)imaging was used to explore the regulatory effect of constraint-induced movement therapy(CIMT)on motor function of rats with cerebral ischemia-reperfusion injury.Methods:The modified Longa's method was used to prepare the left middle cerebral artery occlusion(MCAO)reperfusion injury rats model.After modeling,the rats were randomly divided into control group and CIMT group,with six rats in each group.The rats moved freely in the cage in the control group;CIMT intervention was performed in the CIMT group after modeling at the 7th day,in which the rat's unaffected side was immobilized,and the affected side was forced to move on the treadmill,once a day,20 minutes a time,seven days a week,lasting for two weeks.Before and after CIMT intervention,the open field test was used to evaluate the motor function;the modified neurological severity score(mNSS)was used to evaluate the neurological deficits;9.4 T small animal MRS imaging was used to detect the changes of glutamate andγ-aminobutyric acid levels in the M1 area of the bilateral motor cortex of rats.Results:(1)Motor function:compared with the control group,the total distance of spontaneous locomotor activity in the CIMT group significantly increased after intervention,and the difference was statistically significant(P<0.05).(2)mNSS score results:compared with the control group,the mNSS in the CIMT group significantly decreased after intervention,and the differences were statistically significant(P<0.05).(3)Comparison of glutamate andγ-aminobutyric acid levels in the M1 area of the motor cortex:compared with that before intervention,the ratio of glutamate/creatinine in the M1 area of the contralesional motor cortex significantly decreased in the control group,and the ratio of glutamate/creatinine in the M1 area of the affected side in the CIMT group after intervention significantly increased,the ratio ofγ-aminobutyric acid/creatinine significantly decreased(P<0.05).Compared with the control group,the ratio of glutamate/creatinine in the M1 area of the affected motor cortex in the CIMT group significantly increased,and the ratio ofγ-aminobutyric acid/creatinine significantly decreased(P<0.05).Conclusion:CIMT can improve motor dysfunction and neurological deficit of rats with cerebral ischemia-reperfusion injury,and its mechanism may be related to increase the level of excitatory neurotransmitter glutamate in M1 area of motor cortex and reduce the level of inhibitory neurotransmitterγ-aminobutyric acid.