目的:观察疏肝和胃汤对抑郁模型大鼠延髓、脊髓及胃黏膜组织5-羟色胺(5-hydroxytryptamine,5-HT)表达的影响,部分揭示疏肝和胃汤改善抑郁状态及胃肠功能作用中的5-HT调节机制.方法:100只大鼠随机分成生理盐水组、模型组、百优解组及疏...目的:观察疏肝和胃汤对抑郁模型大鼠延髓、脊髓及胃黏膜组织5-羟色胺(5-hydroxytryptamine,5-HT)表达的影响,部分揭示疏肝和胃汤改善抑郁状态及胃肠功能作用中的5-HT调节机制.方法:100只大鼠随机分成生理盐水组、模型组、百优解组及疏肝和胃汤大、小剂量组.采用慢性心理应激加孤养法制作抑郁模型,共计造模4 wk.在第3周,百优解组及疏肝和胃汤大、小剂量组分别予以0.36mg/(kg·d)、20、10 g/(kg·d)体质量给药,生理盐水组及模型组给予等体积生理盐水,每天分2次灌胃.在第4周结束后,使用内固定法取大鼠延髓迷走神经背核部位的脑、胸髓(T6-T8,根据脊神经定位)及胃黏膜组织,应用免疫组织化学技术检测上述部位5-HT的表达.结果:模型组大鼠延髓组织5-HT含量较生理盐水组显著下降(3314.46±757.47 vs10050.01±472.82),差异具有显著统计学意义(P<0.01);模型组大鼠脊髓与胃黏膜组织5-HT含量较生理盐水组显著上升(7014.51±628.93 vs 4135.62±148.01、4400.12±315.78vs 3614.59±210.54),差异具有显著统计学意义(P<0.01).治疗2 wk后,疏肝和胃汤大、小剂量组和百优解组大鼠延髓中5-HT含量与模型组比较显著增加(9556.06±406.73 vs 3314.46±757.47、7800.91±264.37 vs 3314.46±757.47、9770.94±339.23 v s 3314.46±757.47),差异具有显著统计学意义(P<0.01),脊髓与胃黏膜中5-HT含量与模型组比较显著下降(4487.24±160.55 vs 7014.51±628.93、5667.02±294.84 v s 7014.51±628.93、4908.46±129.58 v s 7014.51±628.93、3736.45±242.36 v s 4400.12±315.78、3978.35±355.96 v s 4400.12±315.78、3826.96±474.88 vs 4400.12±315.78),差异具有统计学意义(P<0.05或P<0.01).其中,疏肝和胃汤大剂量组与百优解组延髓中5-HT含量比较,差异无统计学意义(P>0.05),而疏肝和胃汤大剂量降低脊髓与胃黏膜中5-HT含量的作用较百优解更为明显(4487.24±160.55 vs 4908.46±129.58、3736.45±242.36vs 3826.96±474.88),差异具有统计学意义(P<0.05).结论:疏肝和胃汤可能是通过增加延髓中5-HT的表达,降低脊髓与胃黏膜中5-HT的表达,双向调节"脑(延髓)-脊髓-胃"脑肠轴通路中5-HT的含量,达到改善抑郁状态与胃肠功能的作用.展开更多
Proteoglycans in the central nervous system play integral roles as ＂traffic signals＂ for the direction of neurite outgrowth. This attribute of proteoglycans is a major factor in regeneration of the injured central n...Proteoglycans in the central nervous system play integral roles as ＂traffic signals＂ for the direction of neurite outgrowth. This attribute of proteoglycans is a major factor in regeneration of the injured central nervous system. In this review, the structures of proteoglycans and the evidence suggesting their involvement in the response following spinal cord injury are presented. The review further describes the methods routinely used to determine the effect proteoglycans have on neurite outgrowth. The effects of proteoglycans on neurite outgrowth are not completely understood as there is disagreement on what component of the molecule is interacting with growing neurites and this ambiguity is chronicled in an historical context. Finally, the most recent findings suggesting possible receptors, interactions, and sulfation patterns that may be important in eliciting the effect of proteoglycans on neurite outgrowth are discussed. A greater understanding of the proteoglycan-neurite interaction is necessary for successfully promoting regeneration in the iniured central nervous system.展开更多
Myelin regeneration is indispensably important for patients suffering from several central nervous system （CNS） disorders such as multiple sclerosis （MS） and spinal cord injury （SCI）, because it is not only esse...Myelin regeneration is indispensably important for patients suffering from several central nervous system （CNS） disorders such as multiple sclerosis （MS） and spinal cord injury （SCI）, because it is not only essential for restoring neurophysiology, but also protects denuded axons for secondary degeneration. Understanding the cellular and molecular mechanisms underlying remyelination is critical for the development of remyelination-specific therapeutic approaches. As remyelination shares certain common mechanisms with developmental myelination, knowledge from study of developmental myelination contributes greatly to emerging myelin regeneration therapies, best evidenced as the recently developed human anti-Nogo receptor interacting protein-1 （LINGO-1） monoclonal antibodies to treat MS patients in clinical trials.展开更多
As most spinal cord injuries （SCIs） are incomplete, an important target for promoting neural repair and recovery of lost motor function is to promote the connections of spared descending spinal pathways with spinal ...As most spinal cord injuries （SCIs） are incomplete, an important target for promoting neural repair and recovery of lost motor function is to promote the connections of spared descending spinal pathways with spinal motor circuits. Among the pathways, the corticospinal tract （CST） is most associated with skilled voluntary functions in humans and many animals. CST loss, whether at its origin in the motor cortex or in the white matter tracts subcortically and in the spinal cord, leads to movement impairments and paraly- sis. To restore motor function after injury will require repair of the damaged CST. In this review, I discuss how knowledge of activity-dependent development of the CST--which establishes connectional speci- ficity through axon pruning, axon outgrowth, and synaptic competition among CST terminals--informed a novel activity-based therapy for promoting sprouting of spared CST axons after injur in mature animals. This therapy, which comprises motor cortex electrical stimulation with and without concurrent trans-spi- nal direct current stimulation, leads to an increase in the gray matter axon length of spared CST axons in the rat spinal cord and, after a pyramidal tract lesion, restoration of skilled locomotor movements. I discuss how this approach is now being applied to a C4 contusion rat model.展开更多
文摘目的:观察疏肝和胃汤对抑郁模型大鼠延髓、脊髓及胃黏膜组织5-羟色胺(5-hydroxytryptamine,5-HT)表达的影响,部分揭示疏肝和胃汤改善抑郁状态及胃肠功能作用中的5-HT调节机制.方法:100只大鼠随机分成生理盐水组、模型组、百优解组及疏肝和胃汤大、小剂量组.采用慢性心理应激加孤养法制作抑郁模型,共计造模4 wk.在第3周,百优解组及疏肝和胃汤大、小剂量组分别予以0.36mg/(kg·d)、20、10 g/(kg·d)体质量给药,生理盐水组及模型组给予等体积生理盐水,每天分2次灌胃.在第4周结束后,使用内固定法取大鼠延髓迷走神经背核部位的脑、胸髓(T6-T8,根据脊神经定位)及胃黏膜组织,应用免疫组织化学技术检测上述部位5-HT的表达.结果:模型组大鼠延髓组织5-HT含量较生理盐水组显著下降(3314.46±757.47 vs10050.01±472.82),差异具有显著统计学意义(P<0.01);模型组大鼠脊髓与胃黏膜组织5-HT含量较生理盐水组显著上升(7014.51±628.93 vs 4135.62±148.01、4400.12±315.78vs 3614.59±210.54),差异具有显著统计学意义(P<0.01).治疗2 wk后,疏肝和胃汤大、小剂量组和百优解组大鼠延髓中5-HT含量与模型组比较显著增加(9556.06±406.73 vs 3314.46±757.47、7800.91±264.37 vs 3314.46±757.47、9770.94±339.23 v s 3314.46±757.47),差异具有显著统计学意义(P<0.01),脊髓与胃黏膜中5-HT含量与模型组比较显著下降(4487.24±160.55 vs 7014.51±628.93、5667.02±294.84 v s 7014.51±628.93、4908.46±129.58 v s 7014.51±628.93、3736.45±242.36 v s 4400.12±315.78、3978.35±355.96 v s 4400.12±315.78、3826.96±474.88 vs 4400.12±315.78),差异具有统计学意义(P<0.05或P<0.01).其中,疏肝和胃汤大剂量组与百优解组延髓中5-HT含量比较,差异无统计学意义(P>0.05),而疏肝和胃汤大剂量降低脊髓与胃黏膜中5-HT含量的作用较百优解更为明显(4487.24±160.55 vs 4908.46±129.58、3736.45±242.36vs 3826.96±474.88),差异具有统计学意义(P<0.05).结论:疏肝和胃汤可能是通过增加延髓中5-HT的表达,降低脊髓与胃黏膜中5-HT的表达,双向调节"脑(延髓)-脊髓-胃"脑肠轴通路中5-HT的含量,达到改善抑郁状态与胃肠功能的作用.
基金supported by the NIH(NS53470)the Kentucky Spinal Cord and Head Injury Research Trust(#10-11A)the Department of Defense,CDMRP(SC090248/W81XWH-10-1-0778)
文摘Proteoglycans in the central nervous system play integral roles as ＂traffic signals＂ for the direction of neurite outgrowth. This attribute of proteoglycans is a major factor in regeneration of the injured central nervous system. In this review, the structures of proteoglycans and the evidence suggesting their involvement in the response following spinal cord injury are presented. The review further describes the methods routinely used to determine the effect proteoglycans have on neurite outgrowth. The effects of proteoglycans on neurite outgrowth are not completely understood as there is disagreement on what component of the molecule is interacting with growing neurites and this ambiguity is chronicled in an historical context. Finally, the most recent findings suggesting possible receptors, interactions, and sulfation patterns that may be important in eliciting the effect of proteoglycans on neurite outgrowth are discussed. A greater understanding of the proteoglycan-neurite interaction is necessary for successfully promoting regeneration in the iniured central nervous system.
基金supported by grants from NIH(R01NS080844)Michel J.Fox foundation,Intramural Research Support Programby funds from the Department of Pediatrics,University of Mississippi Medical Center
文摘Myelin regeneration is indispensably important for patients suffering from several central nervous system （CNS） disorders such as multiple sclerosis （MS） and spinal cord injury （SCI）, because it is not only essential for restoring neurophysiology, but also protects denuded axons for secondary degeneration. Understanding the cellular and molecular mechanisms underlying remyelination is critical for the development of remyelination-specific therapeutic approaches. As remyelination shares certain common mechanisms with developmental myelination, knowledge from study of developmental myelination contributes greatly to emerging myelin regeneration therapies, best evidenced as the recently developed human anti-Nogo receptor interacting protein-1 （LINGO-1） monoclonal antibodies to treat MS patients in clinical trials.
基金Support provided by grants from the National Institutes of Health R01NS064004the New York State Department of Health Spinal Cord Injury Board C30606GG,C30835GG
文摘As most spinal cord injuries （SCIs） are incomplete, an important target for promoting neural repair and recovery of lost motor function is to promote the connections of spared descending spinal pathways with spinal motor circuits. Among the pathways, the corticospinal tract （CST） is most associated with skilled voluntary functions in humans and many animals. CST loss, whether at its origin in the motor cortex or in the white matter tracts subcortically and in the spinal cord, leads to movement impairments and paraly- sis. To restore motor function after injury will require repair of the damaged CST. In this review, I discuss how knowledge of activity-dependent development of the CST--which establishes connectional speci- ficity through axon pruning, axon outgrowth, and synaptic competition among CST terminals--informed a novel activity-based therapy for promoting sprouting of spared CST axons after injur in mature animals. This therapy, which comprises motor cortex electrical stimulation with and without concurrent trans-spi- nal direct current stimulation, leads to an increase in the gray matter axon length of spared CST axons in the rat spinal cord and, after a pyramidal tract lesion, restoration of skilled locomotor movements. I discuss how this approach is now being applied to a C4 contusion rat model.
