不同电流强度刺激下单侧纹状体和单侧内侧前脑束损毁的帕金森病大鼠模型的行为学表现

Behavior of parkinsonian rats with unilateral striatal lesion and medial forebrain bundle lesion under stimulation with different current intensities

目的比较6-羟基多巴胺(6-OHDA)损毁单侧纹状体和单侧内侧前脑束(MFB)帕金森病(PD)大鼠模型以不同电流强度行丘脑底核(STN)脑深部电刺激术(DBS)后的行为学差异。方法将24只成年雄性SD大鼠随机分为1位点纹状体损毁组(n=12)和MFB损毁组(n=12)。对两组大鼠模型分别以0、100、150和200μA逐步增加的电流强度行STN-DBS治疗,比较两组在甲基苯丙胺诱导的旋转实验、步行实验和旋转棒实验中的不同表现。结果在甲基苯丙胺诱导的旋转实验中,电流强度达到200μA时,MFB损毁组的旋转圈数降至(0.7±0.5)r/min,而1位点纹状体损毁组则完全停止了旋转(0 r/min),与150μA刺激时相比,两组模型的旋转症状都得到了显著改善(P<0.01)。在步行实验和旋转棒实验中,电流强度达到150μA时,与100μA刺激时相比,1位点纹状体损毁组和MFB损毁组启动时间分别显著缩短为(4.2±1.8)s和(18±2.3)s,平均步长长度分别显著增加为(14.6±0.6)cm和(14.8±0.8)cm,步伐调整数(前进)分别显著增加为(4.5±0.5)步和(4.2±0.4)步,步伐调整数(后退)分别显著增加为(11.2±0.3)步和(11.4±0.4)步;旋转棒实验综合成绩结果(ORP)分别提高为(3405±572)分和(2904±931)分;运动障碍症状都得到显著改善(P<0.01)。结论在PD大鼠模型STN-DBS治疗实验中,不同症状获得显著治疗效果的电刺激参数是不同的,应根据不同实验目的,选取合适的行为学实验方法来筛选最佳电刺激参数。

Objective To compare the behavioral differences in Parkinson's disease(PD)rat models with 6-hydroxydopamine lesions of the unilateral striatum and the unilateral medial forebrain bundle(MFB)after deep brain stimulation of the subthalamic nucleus(STN-DBS)with different current intensities.Methods Twenty-four adult male Sprague-Dawley(SD)rats were randomly divided into two groups,1-site striatum lesion model group(n=12)and MFB lesion model group(n=12).Both groups were treated with STN-DBS at incrementally increasing current intensities of 0,100,150 and 200μA.The differences in behavioral performance were compared using methamphetamine-induced rotational test,walking test and rotarod test.Results During methamphetamine-induced rotational test,when the current intensity reached 200μA,the rotation count of the MFB lesion group decreased to(0.7±0.5)r/min,while the rotation of the 1-site striatum lesion group completely stopped(0 r/min).Compared to stimulation at 150μA,the rotation symptoms of both groups were significantly improved(P<0.01).During walking test and rotarod test,when the current intensity reached 150μA,compared to 100μA stimulation,the initiation time in the 1-site striatum lesion group and the MFB lesion group significantly shortened to(4.2±1.8)s and(18±2.3)s,respectively.The average step length significantly increased to(14.6±0.6)cm and(14.8±0.8)cm,respectively.The number of step adjustments(forward)increased significantly to(4.5±0.5)and(4.2±0.4)steps,respectively.Step adjustments(backward)increased significantly to(11.2±0.3)and(11.4±0.4)steps,respectively.The ORP of rotarod test increased to(3405±572)and(2904±931)scores,respectively.The symptoms of movement disorders were significantly improved(P<0.01).Conclusion The electrical stimulation parameters for obtaining significant therapeutic effects in the STN-DBS treatment experiments on PD rat models are different for different symptoms.According to different experimental objectives,appropriate behavioral experimental methods should be selected to screen the best electrical stimulation parameters.