We established a stroke-prone renovascular hypertensive rat model by bilateral constriction of the renal artery with sliver loop clips. After ten weeks, middle cerebral artery occlusion was induced for 2 hours. The ra...We established a stroke-prone renovascular hypertensive rat model by bilateral constriction of the renal artery with sliver loop clips. After ten weeks, middle cerebral artery occlusion was induced for 2 hours. The rats then received electro-acupuncture at Baihui （DU 20） and Dazhui （DU 14） after onset of ischemia for 30 days. In situ hybridization study showed that electroacupuncture significantly reduced the number of neurocan mRNA-positive cells in the ischemic penumbra and hippocampal tissues of rats. Electron microscopy results demonstrated that the structure of neurons and blood vessels in the ischemic tissues were restored with electroacupuncture. Overall, these data suggest that electroacupuncture may protect neurons against ischemic reperfusion injury in stroke-prone renovascular hypertensive rats, which may be regulated by downregulation of expression of nerve inhibitory factor neurocan mRNA.展开更多
BACKGROUND： Inhibitory signals, i.e. neurite growth inhibitors （NGIs）, presenting on central nervous system （CNS） myelin have been shown to play a crucial role in inhibiting lesioned axonal sprouting and leading ...BACKGROUND： Inhibitory signals, i.e. neurite growth inhibitors （NGIs）, presenting on central nervous system （CNS） myelin have been shown to play a crucial role in inhibiting lesioned axonal sprouting and leading to less functional recovery. Vaccines targeting NGIs may provide multifactorial protection against brain insults by overcoming the inhibitory effects of these NGIs and boosting the body＇s immune repair mechanisms. OBJECTIVE： To evaluate the effect of poststroke DNA immunization against NGIs on the rehabilitation for sensorimotor function of rat models of local cerebral ischemia. DESIGN： Completely randomized grouping design, and controlled experiment. SETTING： Brain Injury Research Laboratory, Department of Neurosurgery, National Neuroscience Institute, Singapore. MATERIALS： Sixty adult male Sprague-Dawley rats ranging in age from 45 to 120 days and in weight from 180 to 250 grams were provided by Animal Center of Department of Anatomy, Faculty of Medicine, National University of Singapore. pcDNA3.1（＋）-neurite growth inhibitors （pcDNA-NGIs） a gift was provided by Dr. Xiao from Department of Clinical Research, Singapore General Hospital, Singapore. METHODS： The experiment was carried out at Brain Injury Research Laboratory, Department of Neurosurgery, National Neuroscience Institute, Singapore from August 2003 to April 2005. （1）The involved rats were randomized into 3 groups： pcDNA-NGIs group （group A）, pcDNA3.1 （＋） group （group B） and model group （group C）, with 20 rats in each group. Left focal cerebral ischemia （FCI） was permanently induced through middle cerebral artery occlusion （MCAO） with the assistance of an operating microscope. Successful MCAO was determined by a 20% decrease to baseline in the ipsilateral cerebral blood flow. 100 μg of pcDNA-NGIs eluted in phosphate-buffered saline （PBS） was intramuscularly injected into the tibial muscle once a week after MCAO for 6 weeks in group A. As control, pcDNA3.1 （＋） was also administrated in the same way in group B and nothing was administrated in group C. （2） The modified neurological severity score （mNSS）, a composite of motor, sensory, reflex and balance tests, was used to test the sensorimotor deficit. The mNSS was graded on a scale of 0 - 18, i.e. normal score was 0, maximal deficit score was 18, and 1 point was warded for the inability to perform the tasks or the lack of a tested reflex. （3） The newly generated axons of corticorubral projection were traced by stereotaxic guided injection of 100 g/L biotinylated dextran amine. Rats were sacrificed two weeks after tracing, and cryostat coronal sections of midbrains （30μm） were reacted to BDA according to the manufacturer＇s instruction by the free-floating method. Images were captured on a DM RXA2 LEICA Microscope with a Spot Digital Camera system （Germany）, and the numbers of labeled axons on the denervated side in four standard coronal sections including the red nucleus were manually quantified. MAIN OUTCOME MEASURES： （1） The number of newly generated axons of corticorubral projection. （2）The improvement in sensorimotor deficit. RESULTS： All the involved 60 rats entered the stage of final analysis. （1） The number of newly generated axons of corticorubral projection of rats： Only ipsilateral axons of CRP were noted with little evidence of fibers crossing to the contralateral red nucleus in rats of groups B and C. More BDA-positive fibers crossing the midline and terminating in the contralateral red nucleus in appropriate target areas mirroring the non-differentiated red nucleus were found in rats of group A. Quantitative analysis showed that BDA-labeled axons in the denervated side of rats in group A were more than those in group B （P 〈 0.05）. （2） Improvement in sensorimotor deficit of rats： At 2 weeks after immunization, significant improvement in sensorimotor deficit was found in rats of group A. There were significant differences of improvement in sensorimotor deficit of rats between group A and group B or group C at 12 and 14 weeks after immunization （P 〈 0.05）. CONCLUSION： （1） Poststroke DNA immunization against NGIs leads to increased sensorimotor recovery following FCI and compensatory newly growth of axons from corticorubral projection.展开更多
BACKGROUND： Inhibitory signals, i.e. neurite growth inhibitors （NGIs）, presenting on central nervous system （CNS） myelin have been shown to play a crucial role in inhibiting lesioned axonal sprouting and leading ...BACKGROUND： Inhibitory signals, i.e. neurite growth inhibitors （NGIs）, presenting on central nervous system （CNS） myelin have been shown to play a crucial role in inhibiting lesioned axonal sprouting and leading to less functional recovery. Vaccines targeting NGIs may provide multifactorial protection against brain insults by overcoming the inhibitory effects of these NGIs and boosting the immune repair mechanisms of body. OBJECTIVE： To evaluate the effect of pre-stroke DNA immunization against NGIs on the rehabilitation for sensorimotor function of rat models of focal cerebral ischemia. DESIGN： A completely randomized design, and controlled experiment. SETTING： Brain Injury Research Laboratory, Department of Neurosurgery, National Neuroscience Institute, Singapore. MATERIALS： Sixty adult male Sprague-Dawley rats ranging in age from 45 to 120 days and in body mass from 180 to 250 g were provided by the Animal Center of Department of Anatomy, Faculty of Medicine, National University of Singapore. pcDNA3.1（＋）-neurite growth inhibitors （pcDNA-NGIs） a gift was provided by Dr. Xiao from the Department of Clinical Research, Singapore General Hospital, Singapore. METHODS： The experiment was carried out at Brain Injury Research Laboratory, Department of Neurosurgery, National Neuroscience Institute, Singapore from August 2003 to April 2005. ① The involved rats were randomized into 3 groups： model group （group A）, pcDNA3.1（＋） group （group B） and pcDNA-NGIs group （group C）, with 20 rats in each group. Left focal cerebral ischemia was permanently induced through middle cerebral artery occlusion with the assistance of an operating microscope. Successful middle cerebral artery occlusion was determined by a 20% decrease to baseline in the ipsilateral cerebral blood flow. 100 μg of pcDNA-NGIs eluted in phosphate-buffered saline （PBS） was intramuscularly injected into the tibial muscle once a week before middle cerebral artery occlusion for 6 weeks in group C. As control, pcDNA3.1 （＋） was also administrated in the same way in group B and nothing was administrated in group A. ② The modified neurological severity score （mNSS）, a composite of motor, sensory, reflex and balance tests, was used to test the sensorimotor deficit. The mNSS was graded on 0-18, i.e. normal score was 0, maximal deficit score was 18, and 1 point was warded for the inability to perform the tasks or the lack of a tested reflex. ③ The newly generated axons of corticorubral projection were traced by stereotaxic guided injection of 100 g/L biotinylated dextran amine （BDA）. Rats were sacrificed two weeks after tracing, and cryostat coronal sections of midbrains （30 μm） were reacted to BDA according to the manufacturer＇s instruction by the free-floating method. Images were captured on a DM RXA2 LEICA Microscope with a Spot Digital Camera system （Germany）, and the numbers of labeled axons on the denervated side in four standard coronal sections including the red nucleus were manually quantified. MAIN OUTCOME MEASURES： ① The number of newly generated axons of corticorubral projection; ② The improvement of the sensorimotor deficit. RESULTS： All the involved 60 rats entered the final analysis. ① The number of newly generated axons of corticorubral projection of rats： Only ipsilateral axons of corticorubral projiction were noted with little evidence of fibers crossing to the contralateral red nucleus in rats of groups A and B. More BDA-positive fibers crossing the midline and terminating in the contralateral red nucleus in appropriate target areas mirroring the non-differentiated red nucleus were found in rats of group C. Quantitative analysis showed that BDA-labelled axons in the denervated side of rats in group C were more than those in group B （P 〈 0.05）. ② The improvement of the sensorimotor deficit： At two weeks after middle cerebral artery occlusion, significant improvement in sensorimotor deficit was found in rats of group C. There was significant difference of improvement in sensorimotor deficit of rats between group C and group B or group A at eight and 10 weeks after middle cerebral artery occlusion （P 〈 0.05）. CONCLUSION： Pre-stroke DNA immunization against NGIs led to increased sensorimotor recovery following focal cerebral ischemia and compensatory newly growth of axons from corticorubral projection.展开更多
目的系统评价远隔缺血后适应对缺血性脑卒中患者神经功能及预后的影响。方法使用计算机系统检索Pubmed、Web of Science、embase、Cochrane图书馆、中国知网(CNKI)、维普网(VIP)、万方数据知识服务平台(Wanfang Data)、中国生物医学文...目的系统评价远隔缺血后适应对缺血性脑卒中患者神经功能及预后的影响。方法使用计算机系统检索Pubmed、Web of Science、embase、Cochrane图书馆、中国知网(CNKI)、维普网(VIP)、万方数据知识服务平台(Wanfang Data)、中国生物医学文献数据库(CBM)有关于远隔缺血后适应治疗缺血性脑卒中的随机对照试验,干预组采用RIPostC进行治疗,对照组采用常规药物治疗,结局指标包括美国国立卫生研究院卒中量表(NIHSS)评分、Barthel指数(BI)评分以及改良Rankin(mRS)评分。检索时间为建库至2023年7月,将符合条件的文献进行Meta分析。结果总共纳入9篇文献,共包括998名缺血性脑卒中患者。Meta分析结果显示,干预组的NIHSS评分低于对照组[MD=-2.30,95%CI(-2.99,-1.62)],BI评分高于对照组[MD=9.40,95%CI(4.56,14.23)],mRS评分低于对照组[MD=-0.42,95%CI(-0.76,-0.08)]。结论远隔缺血后适应能够减轻IRI,有效改善缺血性脑卒中患者的神经功能,提高患者的日常生活自理能力。但本研究纳入文献较少,样本量较小,今后还需要开展更多大样本、多中心、高质量的随机对照试验进行验证。展开更多
基金Research Projects of Science and Technology Bureau of Foshan City, No. 04080131the Administration Bureau of Traditional Chinese Medicine of Guangdong Province, No. 1050006the Natural Science Foundation of Guangdong Province, No. 8152800007000001
文摘We established a stroke-prone renovascular hypertensive rat model by bilateral constriction of the renal artery with sliver loop clips. After ten weeks, middle cerebral artery occlusion was induced for 2 hours. The rats then received electro-acupuncture at Baihui （DU 20） and Dazhui （DU 14） after onset of ischemia for 30 days. In situ hybridization study showed that electroacupuncture significantly reduced the number of neurocan mRNA-positive cells in the ischemic penumbra and hippocampal tissues of rats. Electron microscopy results demonstrated that the structure of neurons and blood vessels in the ischemic tissues were restored with electroacupuncture. Overall, these data suggest that electroacupuncture may protect neurons against ischemic reperfusion injury in stroke-prone renovascular hypertensive rats, which may be regulated by downregulation of expression of nerve inhibitory factor neurocan mRNA.
基金the grants from the National Medical Research Council and Health Research of Singapore
文摘BACKGROUND： Inhibitory signals, i.e. neurite growth inhibitors （NGIs）, presenting on central nervous system （CNS） myelin have been shown to play a crucial role in inhibiting lesioned axonal sprouting and leading to less functional recovery. Vaccines targeting NGIs may provide multifactorial protection against brain insults by overcoming the inhibitory effects of these NGIs and boosting the body＇s immune repair mechanisms. OBJECTIVE： To evaluate the effect of poststroke DNA immunization against NGIs on the rehabilitation for sensorimotor function of rat models of local cerebral ischemia. DESIGN： Completely randomized grouping design, and controlled experiment. SETTING： Brain Injury Research Laboratory, Department of Neurosurgery, National Neuroscience Institute, Singapore. MATERIALS： Sixty adult male Sprague-Dawley rats ranging in age from 45 to 120 days and in weight from 180 to 250 grams were provided by Animal Center of Department of Anatomy, Faculty of Medicine, National University of Singapore. pcDNA3.1（＋）-neurite growth inhibitors （pcDNA-NGIs） a gift was provided by Dr. Xiao from Department of Clinical Research, Singapore General Hospital, Singapore. METHODS： The experiment was carried out at Brain Injury Research Laboratory, Department of Neurosurgery, National Neuroscience Institute, Singapore from August 2003 to April 2005. （1）The involved rats were randomized into 3 groups： pcDNA-NGIs group （group A）, pcDNA3.1 （＋） group （group B） and model group （group C）, with 20 rats in each group. Left focal cerebral ischemia （FCI） was permanently induced through middle cerebral artery occlusion （MCAO） with the assistance of an operating microscope. Successful MCAO was determined by a 20% decrease to baseline in the ipsilateral cerebral blood flow. 100 μg of pcDNA-NGIs eluted in phosphate-buffered saline （PBS） was intramuscularly injected into the tibial muscle once a week after MCAO for 6 weeks in group A. As control, pcDNA3.1 （＋） was also administrated in the same way in group B and nothing was administrated in group C. （2） The modified neurological severity score （mNSS）, a composite of motor, sensory, reflex and balance tests, was used to test the sensorimotor deficit. The mNSS was graded on a scale of 0 - 18, i.e. normal score was 0, maximal deficit score was 18, and 1 point was warded for the inability to perform the tasks or the lack of a tested reflex. （3） The newly generated axons of corticorubral projection were traced by stereotaxic guided injection of 100 g/L biotinylated dextran amine. Rats were sacrificed two weeks after tracing, and cryostat coronal sections of midbrains （30μm） were reacted to BDA according to the manufacturer＇s instruction by the free-floating method. Images were captured on a DM RXA2 LEICA Microscope with a Spot Digital Camera system （Germany）, and the numbers of labeled axons on the denervated side in four standard coronal sections including the red nucleus were manually quantified. MAIN OUTCOME MEASURES： （1） The number of newly generated axons of corticorubral projection. （2）The improvement in sensorimotor deficit. RESULTS： All the involved 60 rats entered the stage of final analysis. （1） The number of newly generated axons of corticorubral projection of rats： Only ipsilateral axons of CRP were noted with little evidence of fibers crossing to the contralateral red nucleus in rats of groups B and C. More BDA-positive fibers crossing the midline and terminating in the contralateral red nucleus in appropriate target areas mirroring the non-differentiated red nucleus were found in rats of group A. Quantitative analysis showed that BDA-labeled axons in the denervated side of rats in group A were more than those in group B （P 〈 0.05）. （2） Improvement in sensorimotor deficit of rats： At 2 weeks after immunization, significant improvement in sensorimotor deficit was found in rats of group A. There were significant differences of improvement in sensorimotor deficit of rats between group A and group B or group C at 12 and 14 weeks after immunization （P 〈 0.05）. CONCLUSION： （1） Poststroke DNA immunization against NGIs leads to increased sensorimotor recovery following FCI and compensatory newly growth of axons from corticorubral projection.
基金the grants from the National Medical Research Council and Singhealth Research of Singapore
文摘BACKGROUND： Inhibitory signals, i.e. neurite growth inhibitors （NGIs）, presenting on central nervous system （CNS） myelin have been shown to play a crucial role in inhibiting lesioned axonal sprouting and leading to less functional recovery. Vaccines targeting NGIs may provide multifactorial protection against brain insults by overcoming the inhibitory effects of these NGIs and boosting the immune repair mechanisms of body. OBJECTIVE： To evaluate the effect of pre-stroke DNA immunization against NGIs on the rehabilitation for sensorimotor function of rat models of focal cerebral ischemia. DESIGN： A completely randomized design, and controlled experiment. SETTING： Brain Injury Research Laboratory, Department of Neurosurgery, National Neuroscience Institute, Singapore. MATERIALS： Sixty adult male Sprague-Dawley rats ranging in age from 45 to 120 days and in body mass from 180 to 250 g were provided by the Animal Center of Department of Anatomy, Faculty of Medicine, National University of Singapore. pcDNA3.1（＋）-neurite growth inhibitors （pcDNA-NGIs） a gift was provided by Dr. Xiao from the Department of Clinical Research, Singapore General Hospital, Singapore. METHODS： The experiment was carried out at Brain Injury Research Laboratory, Department of Neurosurgery, National Neuroscience Institute, Singapore from August 2003 to April 2005. ① The involved rats were randomized into 3 groups： model group （group A）, pcDNA3.1（＋） group （group B） and pcDNA-NGIs group （group C）, with 20 rats in each group. Left focal cerebral ischemia was permanently induced through middle cerebral artery occlusion with the assistance of an operating microscope. Successful middle cerebral artery occlusion was determined by a 20% decrease to baseline in the ipsilateral cerebral blood flow. 100 μg of pcDNA-NGIs eluted in phosphate-buffered saline （PBS） was intramuscularly injected into the tibial muscle once a week before middle cerebral artery occlusion for 6 weeks in group C. As control, pcDNA3.1 （＋） was also administrated in the same way in group B and nothing was administrated in group A. ② The modified neurological severity score （mNSS）, a composite of motor, sensory, reflex and balance tests, was used to test the sensorimotor deficit. The mNSS was graded on 0-18, i.e. normal score was 0, maximal deficit score was 18, and 1 point was warded for the inability to perform the tasks or the lack of a tested reflex. ③ The newly generated axons of corticorubral projection were traced by stereotaxic guided injection of 100 g/L biotinylated dextran amine （BDA）. Rats were sacrificed two weeks after tracing, and cryostat coronal sections of midbrains （30 μm） were reacted to BDA according to the manufacturer＇s instruction by the free-floating method. Images were captured on a DM RXA2 LEICA Microscope with a Spot Digital Camera system （Germany）, and the numbers of labeled axons on the denervated side in four standard coronal sections including the red nucleus were manually quantified. MAIN OUTCOME MEASURES： ① The number of newly generated axons of corticorubral projection; ② The improvement of the sensorimotor deficit. RESULTS： All the involved 60 rats entered the final analysis. ① The number of newly generated axons of corticorubral projection of rats： Only ipsilateral axons of corticorubral projiction were noted with little evidence of fibers crossing to the contralateral red nucleus in rats of groups A and B. More BDA-positive fibers crossing the midline and terminating in the contralateral red nucleus in appropriate target areas mirroring the non-differentiated red nucleus were found in rats of group C. Quantitative analysis showed that BDA-labelled axons in the denervated side of rats in group C were more than those in group B （P 〈 0.05）. ② The improvement of the sensorimotor deficit： At two weeks after middle cerebral artery occlusion, significant improvement in sensorimotor deficit was found in rats of group C. There was significant difference of improvement in sensorimotor deficit of rats between group C and group B or group A at eight and 10 weeks after middle cerebral artery occlusion （P 〈 0.05）. CONCLUSION： Pre-stroke DNA immunization against NGIs led to increased sensorimotor recovery following focal cerebral ischemia and compensatory newly growth of axons from corticorubral projection.
文摘目的系统评价远隔缺血后适应对缺血性脑卒中患者神经功能及预后的影响。方法使用计算机系统检索Pubmed、Web of Science、embase、Cochrane图书馆、中国知网(CNKI)、维普网(VIP)、万方数据知识服务平台(Wanfang Data)、中国生物医学文献数据库(CBM)有关于远隔缺血后适应治疗缺血性脑卒中的随机对照试验,干预组采用RIPostC进行治疗,对照组采用常规药物治疗,结局指标包括美国国立卫生研究院卒中量表(NIHSS)评分、Barthel指数(BI)评分以及改良Rankin(mRS)评分。检索时间为建库至2023年7月,将符合条件的文献进行Meta分析。结果总共纳入9篇文献,共包括998名缺血性脑卒中患者。Meta分析结果显示,干预组的NIHSS评分低于对照组[MD=-2.30,95%CI(-2.99,-1.62)],BI评分高于对照组[MD=9.40,95%CI(4.56,14.23)],mRS评分低于对照组[MD=-0.42,95%CI(-0.76,-0.08)]。结论远隔缺血后适应能够减轻IRI,有效改善缺血性脑卒中患者的神经功能,提高患者的日常生活自理能力。但本研究纳入文献较少,样本量较小,今后还需要开展更多大样本、多中心、高质量的随机对照试验进行验证。
