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1电针对脑卒中肢体痉挛大鼠γ-氨基丁酸代谢酶的影响显示文摘目的:探讨电针通过调控γ-氨基丁酸代谢酶改善脑卒中肢体痉挛大鼠肌张力的作用机制。方法:将24只SD大鼠分为正常组、假手术组、模型组和电针组。用大脑中动脉栓塞法建立局灶性脑缺血模型。电针组造模成功后第3天开始取申脉,照海针刺治疗6天,其余组在同等条件下饲养,不做其他处理。采用Bederson评定神经功能,Ashworth分级评定肌张力,Feeney平衡木评分标准评定运动功能,免疫组化染色SP法、实时定量PCR测定各组标本中GABA-T、SSADH的表达。结果:与模型组相比,治疗后电针组神经功能缺损症状改善(P<0.05);肌张力降低(P<0.05);运动功能提高(P<0.05)。免疫组化染色SP法示GABA-T平均光密度值电针组颈膨大(模型组:0.2256±0.0190;电针组:0.2094±0.0083)和腰膨大中(模型组:0.2163±0.0088;电针组:0.1988±0.0054)较模型组明显下降(P<0.05);而脑干中较模型组表达也有下降趋势(模型组:0.2129±0.0086;电针组:0.2072±0.0119)。实时定量PCR测定SSADHm RNA结果与模型组比较显示电针组脑干(模型组:1.67±0.38;电针组:1.22±0.07)、颈膨大(模型组:1.27±0.28;电针组:0.96±0.09)和腰膨大中(模型组:1.07±0.32;电针组:1.08±0.07)表达均降低(P<0.05)。结论:电针阴阳跷脉腧穴通过降低中枢系统中GABA-T和SSADH的释放使GABA的降解速度减慢,从而增加突触间隙的GABA浓度,增强GABA的抑制作用是改善偏瘫肢体痉挛的可能机制之一。毛雪莲 秦思 金荣疆 朱天民 沈小雨 冯丽娟 2018中国康复医学杂志2018,33,1:24
2Early constraint-induced movement therapy affects behavior and neuronal plasticity in ischemia-injured rat brains显示文摘Constraint-induced movement therapy is an effective rehabilitative training technique used to improve the restoration of impaired upper extremity movement after stroke. However, whether constraint-induced movement therapy is more effective than conventional rehabilitation in acute or sub-acute stroke remains controversial. The aim of the present study was to identify the optimal time to start constraint-induced movement therapy after ischemic stroke and to explore the mechanisms by which constraint-induced movement therapy leads to post-stroke recovery. Sixty-four adult male Sprague-Dawley rats were randomly divided into four groups: sham-surgery group, cerebral ischemia/reperfusion group, early constraint-induced movement therapy group, and late constraint-induced movement therapy group. Rat models of left middle cerebral artery occlusion were established according to the Zea Longa line embolism method. Constraint-induced movement therapy was conducted starting on day 1 or day 14 in the early constraint-induced movement therapy and late constraint-induced movement therapy groups, respectively. To explore the effect of each intervention time on neuromotor function, behavioral function was assessed using a balance beam walking test before surgery and at 8 and 21 days after surgery. The expression levels of brain-derived neurotrophic factor, nerve growth factor and Nogo receptor were evaluated using real time-polymerase chain reaction and western blot assay to assess the effect of each intervention time. The results showed that the behavioral score was significantly lower in the early constraint-induced movement therapy group than in the cerebral ischemia/reperfusion and late constraint-induced movement therapy groups at 8 days. At 21 days, the scores had significantly decreased in the early constraint-induced movement therapy and late constraint-induced movement therapy groups. At 8 days, only mild pyknosis appeared in neurons of the ischemic penumbra in the early constraint-induced movement therapy group, which was distinctly better than in the cerebral ischemia/reperfusion group. At 21 days, only a few vacuolated cells were observed and no obvious inflammatory cells were visible in late constraint-induced movement therapy group, which was much better than at 8 days. The mRNA and protein expression levels of brain-derived neurotrophic factor and nerve growth factor were significantly higher, but expression levels of Nogo receptor were significantly lower in the early constraint-induced movement therapy group compared with the cerebral ischemia/reperfusion and late constraint-induced movement therapy groups at 8 days. The changes in expression levels at 21 days were larger but similar in both the early constraint-induced movement therapy and late constraint-induced movement therapy groups. Besides, the protein nerve growth factor level was higher in the late constraint-induced movement therapy group than in the early constraint-induced movement therapy group at 21 days. These results suggest that both early(1 day) and late(14 days) constraint-induced movement therapy induces molecular plasticity and facilitates functional recovery after ischemic stroke, as illustrated by the histology. The mechanism may be associated with downregulation of Nogo receptor expression and upregulation of brain-derived neurotrophic factor and nerve growth factor expression.Xi-Hua Liu Hong-Yan Bi Jie Cao Shuo Ren Shou-Wei Yue 2019Neural Regeneration Research2019,14,5:11
3改良强制性运动调节脑缺血再灌注模型大鼠运动皮层内神经递质水平的研究显示文摘目的研究改良强制性运动对脑缺血再灌注模型大鼠运动功能恢复的作用及其机制。方法将大鼠随机分为对照组和改良强制性运动疗法(mCIMT)组,每组12只。采用Longa线栓法建立大鼠左侧大脑中动脉栓塞(MCAO)模型。mCIMT组在造模后7 d开始连续训练14 d,使用有弹性的的绷带将健肢绑于前胸,并在强制性转轮设备中进行患肢活动的训练,对照组大鼠不进行mCIMT训练,仅笼内自由活动。在造模后20 d内记录大鼠体质量,通过错步实验评定大鼠的行为学变化。在造模后18 d时处死部分大鼠,使用高效液相色谱法(high performance liquid chromatography, HPLC)检测脑运动皮层和纹状体内单胺类神经递质〔5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIVV)和高香草酸(HVA)〕和氨基酸类神经递质〔天门冬氨酸(ASP)、谷氨酰胺(Gln)、甘氨酸(Gly)、牛磺酸(Tau)、γ氨基丁酸(GABA)〕含量,酶联免疫吸附(ELISA)法检测脑运动皮层和纹状体组织总p70核糖体蛋白S6激酶(p70s6k)蛋白和磷酸化蛋白(p-p70s6k)的表达水平。结果造模后21 d内,与对照组比较,mCIMT组大鼠体质量无明显变化(P>0.05),mCIMT组大鼠在造模后17 d时错步率下降(P<0.05);造模后18 d时,与对照组比较,mCIMT组大鼠运动皮层中单胺类神经递质5-HIVV水平增加(P<0.05),运动皮层中氨基酸类神经递质的相对含量(与Glu之比)除ASP/Glu降低(P<0.05)外,其余氨基酸类神经递质包括Gln、Gly、Tau、GABA与Glu之比均增加(P<0.05或P<0.01)。与对照组比较,mCIMT组大鼠运动皮层中p-p70s6k表达减少(P<0.05)。而对照组与mCIMT组大鼠纹状体中的单胺类神经递质和氨基酸神经递质差异均无统计学意义(P>0.05)。结论 mCIMT具有一定的改善脑缺血再灌注模型大鼠运动功能的效果,其机制可能与提高大鼠脑运动皮层内氨基酸类神经递质和5-HIVV水平、减少p-p70s6k表达有关。高蓓瑶 许东升 谢蓓菁 刘培乐 李策 杜亮 华艳 胡健 白玉龙 2020四川大学学报(医学版)2020,51,5:9
4Motor tract reorganization after acute central nervous system injury: a translational perspective显示文摘Acute central nervous system injuries are among the most common causes of disability worldwide,with widespread social and economic implications.Motor tract injury accounts for the majority of this disability;therefore,there is impetus to understand mechanisms underlying the pathophysiology of injury and subsequent reorganization of the motor tract that may lead to recovery.After acute central nervous system injury,there are changes in the microenvironment and structure of the motor tract.For example,ischemic stroke involves decreased local blood flow and tissue death from lack of oxygen and nutrients.Traumatic injury,in contrast,causes stretching and shearing injury to microstructures,including myelinated axons and their surrounding vessels.Both involve blood-brain barrier dysfunction,which is an important initial event.After acute central nervous system injury,motor tract reorganization occurs in the form of cortical remapping in the gray matter and axonal regeneration and rewiring in the white matter.Cortical remapping involves one cortical region taking on the role of another.cAMP-response-element binding protein is a key transcription factor that can enhance plasticity in the peri-infarct cortex.Axonal regeneration and rewiring depend on complex cell-cell interactions between axons,oligodendrocytes,and other cells.The RhoA/Rho-associated coiled-coil containing kinase signaling pathway plays a central role in axon growth/regeneration through interactions with myelin-derived axonal growth inhibitors and regulation of actin cytoskeletal dynamics.Oligodendrocytes and their precursors play a role in myelination,and neurons are involved through their voltage-gated calcium channels.Understanding the pathophysiology of injury and the biology of motor tract reorganization may allow the development of therapies to enhance recovery after acute central nervous system injury.These include targeted rehabilitation,novel pharmacotherapies,such as growth factors and axonal growth inhibitor blockade,and the implementation of neurotechnologies,such as central nervous system stimulators and robotics.The translation of these advances depends on careful alignment of preclinical studies and human clinical trials.As experimental data mount,the future is one of optimism.Hajime Takase Robert W.Regenhardt 2021Neural Regeneration Research2021,16,6:2
5CIMT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显示文摘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。李莹莹 华艳 余克威 鲍伟奇 王瑜元 胡健 胡世红 白玉龙 2022复旦学报(医学版)2022,49,6:0
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