牛膝多肽促神经生长作用及其相关机制的研究
|
摘要
目的
研究牛膝多肽(Achyranthes bidentata Blum Polypeptides,ABPP)对体外培养的大鼠海马神经元突起生长的促进作用及其对GAP-43和NF-H基因表达的影响,以及与ERK1/2信号转导通路的关系。研究ABPP诱导PC12细胞神经元性分化的作用,初步探讨ABPP对PC12细胞的ERK1/2信号转导途径的影响。观察ABPP对小鼠坐骨神经夹伤后神经再生的影响。
方法
1.以体外原代培养的胎鼠海马神经元为研究模型,通过MTT检测ABPP对海马神经元细胞活性的影响,通过免疫荧光细胞化学法,采用Image-Pro Express软件测量不同浓度ABPP(0.1μg/ml、0.5μg/ml、1.0μg/ml)加药24 h,对海马神经元神经突起生长的影响;通过实时荧光定量PCR法定量分析不同浓度ABPP加药6 h,对海马神经元GAP-43和NF-H基因表达的影响。同时应用ERK特异性拮抗剂PD98059与ABPP共培养海马神经元分析ABPP对海马神经元的作用与ERK1/2信号转导通路的关系。
2.以PC12细胞为研究模型,观察在低血清的情况下不同浓度ABPP(0.25μg/ml、0.5μg/ml、1.0μg/ml)诱导PC12细胞发生的形态学改变,第7 d和第14 d时分别观察细胞分化的形态学改变。通用免疫荧光细胞化学法,观察NF-H在ABPP诱导分化的PC12细胞中的表达,从而鉴定ABPP诱导的分化细胞;为了研究与ABPP促分化有关的信号转导通路,采用Western blotting法观察不同浓度ABPP加药不同作用时间后对低血清培养的PC12细胞ERK活性的影响,同时应用ERK特异性拮抗剂PD98059与ABPP共培养PC12细胞,分析ERK1/2信号转导通路在ABPP对PC12细胞影响中的作用。
3.ICR小鼠50只,雌雄各半,行左侧坐骨神经夹伤术。术后随机分为5组:ABPP低、中、高剂量组(剂量分别为1,4,16 mg/kg),弥可保组(阳性对照,剂量为65μg/kg)及生理盐水组(空白对照,给予等体积生理盐水)。经尾静脉注射给药,每日一次,连续给药21 d。术后定期做足迹试验,损伤后3周记录复合肌动作电位,计算运动神经传导速度;取损伤远端5mm处坐骨神经,进行免疫组织化学染色及透射电镜观察,测定再生神经纤维密度、再生神经纤维直径和髓鞘厚度;取腓肠肌做石蜡切片,染色后测定肌纤维横截面积。
结果
1.MTT结果显示在0.01到10μg/ml范围内,ABPP对海马神经元没有明显毒性。不同浓度ABPP(0.1μg/ml、0.5μg/ml、1.0μg/ml)加药24 h,海马神经元神经突起长度明显增加,存在时间依赖性和剂量反应关系,加药24 h后作用最强,剂量为1μg/ml时作用最佳。ABPP(0.5μg/ml、1.0μg/ml)培养6 h后,海马神经元的GAP-43和NF-H的mRNA表达量与阴性对照组相比是明显升高的。PD98059抑制了ABPP(0.5μg/ml)对海马神经元突起的生长,同时降低了NF-H和GAP-43基因mRNA和蛋白质的表达。并且ABPP促神经生长的作用可能是通过ERK通路产生的。
2.ABPP处理PC12细胞3 d后,部分PC12细胞开始出现神经元样的形态:细胞胞体的皱缩、平展以及可见有明显的类似于神经元突起的生长,细胞停止增殖。随着加药时间延长具有神经元样的细胞逐渐增多,到第7 d时,NGF和ABPP处理组PC12细胞的突起都显著增多,能形成网络;到第14 d时,这种现象愈发显著。加药后第7 d和第14 d,ABPP各浓度组的细胞分化率以及细胞突起长度均明显提高,且存在明显的剂量反应关系。加药第7 d和第14 d,ABPP高剂量组与NGF组的PC12细胞均出现NF-H标记阳性的分化细胞。ABPP在0.25μg/ml、0.5μg/ml、1.0μg/ml剂量范围内作用于低血清培养的PC12细胞2 d,对ERK1/2的激活作用存在明显的剂量反应关系,以1.0mg/ml者作用为最大。当用PD98059抑制MEK1/2的活化时,ABPP对ERK1/2的激活作用被部分阻断。
3.ABPP对小鼠坐骨神经夹伤后的神经功能恢复有促进作用,对SFI的改善存在剂量反应关系。能提高损伤后神经近、远端复合肌动作电位幅度和运动神经动作电位,再生髓鞘的密度、厚度、轴突直径及腓肠肌肌纤维横截面积,均显著优于空白对照组,超微结构观察显示,ABPP组小鼠坐骨神经夹伤段有髓神经纤维的髓鞘形态、厚度及成熟度均优于对照组。
结论
1.ABPP能促进体外培养的海马神经元神经突起的生长,其作用与GAP-43和NF-H基因表达的升高相关,可能是通过ERK1/2信号转导途径实现的。
2.ABPP具有诱导PC12细胞神经元性分化的作用,该作用可能是通过ERK1/2信号转导途径实现的。
3.ABPP能促进小鼠坐骨神经夹伤后的神经再生和功能恢复。
Objective
To determine the effects of ABPP(Achyranthes bidentata Blum Polypeptides) on neurite growth in cultured hippocampal neurons of rats.To study the potential ability of ABPP to induce the neuronal differentiation of PC12 cells and to preliminary investigate the activation of ERK1/2 cascade induced by ABPP.To study the repair effects of ABPP on the crushed sciatic rat nerve in mice.
Methods
1.The cytotoxicity of ABPP was tested with MTT.After 24 h of incubation by different concentrations(0.1μg/ml,0.5μg/ml,1.0μg/ml) of ABPP,the hippocampal neurons were photographed by TCS SP2 confocal microscope with fluorescent immunocytochemistry,and the neurite length was analyzed using the Image-Pro Express software.Real-time quantitative RT-PCR was performed to examine the mRNA levels of GAP-43 and NF-H after 6 h with different concentrations of ABPP.Western blotting were performed to further examine the protein levels of GAP-43 and NF-H in cultured hippocampal neurons after 24 h incubation with different concentrations of ABPP,and detected the activities of ERK1/2 in hippocampal neurons co-culture with ABPP and the MEK1/2 inhibitor,PD98059.
2.By cell culture in the low-concentration of serum,the morphological changes of PC12 cells treated with of ABPP at different concentration(0.25μg/ml、0.5μg/ml、1.0μg/ml) was detected.Fluorescent immunocytochemistry was performed to examine the expression of NF-H,a well-known neuronal marker,in differentiated PC12 cells induced by 1.0μg/ml ABPP.In order to study the signaling pathways involved in the differentiation induced by ABPP,Western blotting was performed to detect the acitvities of ERK1/2 in PC12 cells activated by 1.0μg/ml ABPP after different periods(0h、6h、12h、1d、2d、3d and 7d) using the activated(Diphosphorylated ERK1&2) antibody and mitogen activated protein kinase(MAP Kinase,MAPK,ERK-1 & ERK-2) antibody when PC12 cells were cultured in low-concentration of serum medium.
3.Fifty mice were performed sciatic nerve crush injury operation.After that the animals were randomly divided into 5 groups of 10 animals each and treated tail vein administration as follows:ABPP groups(low,middle and high dose,1,4,16 mg/kg, respectively),Methycobal group(served as positive control) at 65μg/kg and saline group (served as negative control).The treatment lasted for 21d.At different time after nerve crush,a combination of experiments,including walking track analysis, electrophysiological assessments,immunohistochemistry and electron microscopy to the regenerated sciatic nerve,masson trichome staining to the gastrocnemius muscle,as well as morphometric analyses,was carried out to evaluate the regenerative outcomes of ABPP administration.
Results
1.ABPP promoted the neurite growth of cultured hippocampal neurons.Real-time quantitative RT-PCR showed that the mRNA level of GAP-43 and NF-H in cultured hippocampal neurons was up-regulated by ABPP in a dose-dependent manner.Meanwhile, fluorescent immunocytochemistry and Western blotting showed that the protein level of GAP-43 and NF-H was up-regulated by ABPP.ABPP-induced phosphrylation of ERK1/2 was blocked by PD98059.
2.After 3 days treated with ABPP(0.25μg/ml、0.5μg/ml、1.0μg/ml),neuron morphology was observed in PC12 cells:compaction of cell bodies,the outgrowth of neurites,unproliferation.As the time went on,the number of the differentiated PC12 cells increased.At day 7 the differentiated PC12 cells could produced the neurite network and at day 14 the phenomena became mo(?)e obvious.It has been shown that ABPP could promote the differentiation of PC12 by dose-effect relation.ABPP activated ERK1/2 in PC12 cells by dose-effect relation and time-dependent character,with the best concentration of 1.0μg/ml after being co-cultured with PC12 cells for 2 days.And PD98059 significantly inhibited ABPP-induced phosphorylation of ERK1/2.
3.The results indicated that treatment with ABPP at a dose range(1-16 mg/kg) promoted histological regeneration and functional recovery of the injured sciatic nerve and its target muscle,yielding a desired efficacy greater than that by vehicle treatment and close to or even greater at some parameters than that by methylcobalamin,a positive control.
Conclusion
1.ABPP could promote the neurite growth and modulate the expression of GAP-43 and NF-H in cultured hippocampal neurons,suggesting neurotrophic effects of ABPP.
2.ABPP could induce the neuronal differentiation of PC12 cells.The differentiation of PC12 cells induced by ABPP may be mediated through ERK1/2 phosphorylation cascade potentially.
3.Plant polypeptides,ABPP,may be a potential agent in ameliorating the effects of neuropathy caused by sciatic nerve crash.
研究牛膝多肽(Achyranthes bidentata Blum Polypeptides,ABPP)对体外培养的大鼠海马神经元突起生长的促进作用及其对GAP-43和NF-H基因表达的影响,以及与ERK1/2信号转导通路的关系。研究ABPP诱导PC12细胞神经元性分化的作用,初步探讨ABPP对PC12细胞的ERK1/2信号转导途径的影响。观察ABPP对小鼠坐骨神经夹伤后神经再生的影响。
方法
1.以体外原代培养的胎鼠海马神经元为研究模型,通过MTT检测ABPP对海马神经元细胞活性的影响,通过免疫荧光细胞化学法,采用Image-Pro Express软件测量不同浓度ABPP(0.1μg/ml、0.5μg/ml、1.0μg/ml)加药24 h,对海马神经元神经突起生长的影响;通过实时荧光定量PCR法定量分析不同浓度ABPP加药6 h,对海马神经元GAP-43和NF-H基因表达的影响。同时应用ERK特异性拮抗剂PD98059与ABPP共培养海马神经元分析ABPP对海马神经元的作用与ERK1/2信号转导通路的关系。
2.以PC12细胞为研究模型,观察在低血清的情况下不同浓度ABPP(0.25μg/ml、0.5μg/ml、1.0μg/ml)诱导PC12细胞发生的形态学改变,第7 d和第14 d时分别观察细胞分化的形态学改变。通用免疫荧光细胞化学法,观察NF-H在ABPP诱导分化的PC12细胞中的表达,从而鉴定ABPP诱导的分化细胞;为了研究与ABPP促分化有关的信号转导通路,采用Western blotting法观察不同浓度ABPP加药不同作用时间后对低血清培养的PC12细胞ERK活性的影响,同时应用ERK特异性拮抗剂PD98059与ABPP共培养PC12细胞,分析ERK1/2信号转导通路在ABPP对PC12细胞影响中的作用。
3.ICR小鼠50只,雌雄各半,行左侧坐骨神经夹伤术。术后随机分为5组:ABPP低、中、高剂量组(剂量分别为1,4,16 mg/kg),弥可保组(阳性对照,剂量为65μg/kg)及生理盐水组(空白对照,给予等体积生理盐水)。经尾静脉注射给药,每日一次,连续给药21 d。术后定期做足迹试验,损伤后3周记录复合肌动作电位,计算运动神经传导速度;取损伤远端5mm处坐骨神经,进行免疫组织化学染色及透射电镜观察,测定再生神经纤维密度、再生神经纤维直径和髓鞘厚度;取腓肠肌做石蜡切片,染色后测定肌纤维横截面积。
结果
1.MTT结果显示在0.01到10μg/ml范围内,ABPP对海马神经元没有明显毒性。不同浓度ABPP(0.1μg/ml、0.5μg/ml、1.0μg/ml)加药24 h,海马神经元神经突起长度明显增加,存在时间依赖性和剂量反应关系,加药24 h后作用最强,剂量为1μg/ml时作用最佳。ABPP(0.5μg/ml、1.0μg/ml)培养6 h后,海马神经元的GAP-43和NF-H的mRNA表达量与阴性对照组相比是明显升高的。PD98059抑制了ABPP(0.5μg/ml)对海马神经元突起的生长,同时降低了NF-H和GAP-43基因mRNA和蛋白质的表达。并且ABPP促神经生长的作用可能是通过ERK通路产生的。
2.ABPP处理PC12细胞3 d后,部分PC12细胞开始出现神经元样的形态:细胞胞体的皱缩、平展以及可见有明显的类似于神经元突起的生长,细胞停止增殖。随着加药时间延长具有神经元样的细胞逐渐增多,到第7 d时,NGF和ABPP处理组PC12细胞的突起都显著增多,能形成网络;到第14 d时,这种现象愈发显著。加药后第7 d和第14 d,ABPP各浓度组的细胞分化率以及细胞突起长度均明显提高,且存在明显的剂量反应关系。加药第7 d和第14 d,ABPP高剂量组与NGF组的PC12细胞均出现NF-H标记阳性的分化细胞。ABPP在0.25μg/ml、0.5μg/ml、1.0μg/ml剂量范围内作用于低血清培养的PC12细胞2 d,对ERK1/2的激活作用存在明显的剂量反应关系,以1.0mg/ml者作用为最大。当用PD98059抑制MEK1/2的活化时,ABPP对ERK1/2的激活作用被部分阻断。
3.ABPP对小鼠坐骨神经夹伤后的神经功能恢复有促进作用,对SFI的改善存在剂量反应关系。能提高损伤后神经近、远端复合肌动作电位幅度和运动神经动作电位,再生髓鞘的密度、厚度、轴突直径及腓肠肌肌纤维横截面积,均显著优于空白对照组,超微结构观察显示,ABPP组小鼠坐骨神经夹伤段有髓神经纤维的髓鞘形态、厚度及成熟度均优于对照组。
结论
1.ABPP能促进体外培养的海马神经元神经突起的生长,其作用与GAP-43和NF-H基因表达的升高相关,可能是通过ERK1/2信号转导途径实现的。
2.ABPP具有诱导PC12细胞神经元性分化的作用,该作用可能是通过ERK1/2信号转导途径实现的。
3.ABPP能促进小鼠坐骨神经夹伤后的神经再生和功能恢复。
Objective
To determine the effects of ABPP(Achyranthes bidentata Blum Polypeptides) on neurite growth in cultured hippocampal neurons of rats.To study the potential ability of ABPP to induce the neuronal differentiation of PC12 cells and to preliminary investigate the activation of ERK1/2 cascade induced by ABPP.To study the repair effects of ABPP on the crushed sciatic rat nerve in mice.
Methods
1.The cytotoxicity of ABPP was tested with MTT.After 24 h of incubation by different concentrations(0.1μg/ml,0.5μg/ml,1.0μg/ml) of ABPP,the hippocampal neurons were photographed by TCS SP2 confocal microscope with fluorescent immunocytochemistry,and the neurite length was analyzed using the Image-Pro Express software.Real-time quantitative RT-PCR was performed to examine the mRNA levels of GAP-43 and NF-H after 6 h with different concentrations of ABPP.Western blotting were performed to further examine the protein levels of GAP-43 and NF-H in cultured hippocampal neurons after 24 h incubation with different concentrations of ABPP,and detected the activities of ERK1/2 in hippocampal neurons co-culture with ABPP and the MEK1/2 inhibitor,PD98059.
2.By cell culture in the low-concentration of serum,the morphological changes of PC12 cells treated with of ABPP at different concentration(0.25μg/ml、0.5μg/ml、1.0μg/ml) was detected.Fluorescent immunocytochemistry was performed to examine the expression of NF-H,a well-known neuronal marker,in differentiated PC12 cells induced by 1.0μg/ml ABPP.In order to study the signaling pathways involved in the differentiation induced by ABPP,Western blotting was performed to detect the acitvities of ERK1/2 in PC12 cells activated by 1.0μg/ml ABPP after different periods(0h、6h、12h、1d、2d、3d and 7d) using the activated(Diphosphorylated ERK1&2) antibody and mitogen activated protein kinase(MAP Kinase,MAPK,ERK-1 & ERK-2) antibody when PC12 cells were cultured in low-concentration of serum medium.
3.Fifty mice were performed sciatic nerve crush injury operation.After that the animals were randomly divided into 5 groups of 10 animals each and treated tail vein administration as follows:ABPP groups(low,middle and high dose,1,4,16 mg/kg, respectively),Methycobal group(served as positive control) at 65μg/kg and saline group (served as negative control).The treatment lasted for 21d.At different time after nerve crush,a combination of experiments,including walking track analysis, electrophysiological assessments,immunohistochemistry and electron microscopy to the regenerated sciatic nerve,masson trichome staining to the gastrocnemius muscle,as well as morphometric analyses,was carried out to evaluate the regenerative outcomes of ABPP administration.
Results
1.ABPP promoted the neurite growth of cultured hippocampal neurons.Real-time quantitative RT-PCR showed that the mRNA level of GAP-43 and NF-H in cultured hippocampal neurons was up-regulated by ABPP in a dose-dependent manner.Meanwhile, fluorescent immunocytochemistry and Western blotting showed that the protein level of GAP-43 and NF-H was up-regulated by ABPP.ABPP-induced phosphrylation of ERK1/2 was blocked by PD98059.
2.After 3 days treated with ABPP(0.25μg/ml、0.5μg/ml、1.0μg/ml),neuron morphology was observed in PC12 cells:compaction of cell bodies,the outgrowth of neurites,unproliferation.As the time went on,the number of the differentiated PC12 cells increased.At day 7 the differentiated PC12 cells could produced the neurite network and at day 14 the phenomena became mo(?)e obvious.It has been shown that ABPP could promote the differentiation of PC12 by dose-effect relation.ABPP activated ERK1/2 in PC12 cells by dose-effect relation and time-dependent character,with the best concentration of 1.0μg/ml after being co-cultured with PC12 cells for 2 days.And PD98059 significantly inhibited ABPP-induced phosphorylation of ERK1/2.
3.The results indicated that treatment with ABPP at a dose range(1-16 mg/kg) promoted histological regeneration and functional recovery of the injured sciatic nerve and its target muscle,yielding a desired efficacy greater than that by vehicle treatment and close to or even greater at some parameters than that by methylcobalamin,a positive control.
Conclusion
1.ABPP could promote the neurite growth and modulate the expression of GAP-43 and NF-H in cultured hippocampal neurons,suggesting neurotrophic effects of ABPP.
2.ABPP could induce the neuronal differentiation of PC12 cells.The differentiation of PC12 cells induced by ABPP may be mediated through ERK1/2 phosphorylation cascade potentially.
3.Plant polypeptides,ABPP,may be a potential agent in ameliorating the effects of neuropathy caused by sciatic nerve crash.
引文
[1]Flors AJ,Lavemia CJ,Owens PW.Anatomy and physiology of peripheral nerve injury and repair.Am J Orthop.2000,29(3):167-173.
[2]Lee SK,Wolfe SW.Peripheral nerve injury and repair.J Am Acad Orthop Surg.2000,8(4):243-252.
[3]Terenghi G.Peripheral nerve regeneration and neurotrophic factors.J.Anat.1999,194(pt 1):1-14.
[4]Schmidt CE,Leach JB.Neural tissue engineering:strategies for repair and regeneration.Annu Rev Biomed Eng.2003,5:293-347.
[5]Edgar D,Barde YA,Thoenen H.Subpopulations of cultured chick sympathetic neurones differ in their requirements for survival factors.Nature.1981,289(5795):294-295.
[6]Sendtner M,Holtmann B,Kolbeck R,et al.Brain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nerve section.Nature,1992,360(6404):757-759.
[7]Sendtner M,kreutzberg GW,Thoenen H.Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy.Nature,1990,345(6274):440-441.
[8]Reynolds ML,Woolf CJ.Reciprocal Schwann cell-axon interactions.Curr Opin Neurobiol.1993,3(5),683-693.
[9]Simon M,Porter R,Brown R,et al.Effects of NT-4 and BDNF delivery to damaged sciatic nerves on phenotypic recovery of fast and slow muscles fibres.Eur J Neurosci.2003,18(9):2460-2466.
[10]Romero MI,Rangappa N,Garry MG,et al.Functional regeneration of chronically injured sensory afferents into adult spinal cord after neurotrophin gene therapy.J.Neurosci.2001,21(21):8.408-16.
[11]Winter CG,Saotome Y,Levison Sw,et al.A role for ciliary neurotrophic factor as an inducer of reactive gliosis,the glial response to central nervous system injury.Proc Natl Acad Sci USA.1995,92(13):5865-5869.
[12]Gary Walsh.Biopharmaceuticals:Biochemistry and Biotechnology.John Wiley &Sons,Ltd.2003.
[13]Saklani A,Kutty SK.Plant-derived compounds in clinical trials.Drug Discovery Today.2008,13(3-4):161-71.Epub 2007 Nov 26.
[14]中国药典委员会,《中国药典》2005年版.
[1] Jin M, Guan CB, Jiang YA, et al. Ca2+-dependent regulation of Rho GTPases triggers turning of nerve growth cones. J. Neuroscience.2005;25(9): 2338-2347.
[2] Cheung ZH, Chin WH, Chen Y, et al. Cdk5 is involved in BDNF-stimulated dendritic growth in hippocampal neurons. PLoS Biol. 2007;5(4): e63
[3] Ji Y, Pang PT, Feng L, Lu B. Cyclic AMP controls BDNF-induced TrkB phosphorylation and dendritic spine formation in mature hippocampal neurons. Nat Neurosci. 2005;8(2): 164-172.
[4] Yamada K, Nabeshima T. Brain-derived neurotrophic factor/TrkB signaling in memory processes. J Pharmacol Sci. 2003;91(4):267-270.
[5] Holland PM, Abramson RD, Watson R, et al. Detection of specific polymerase chain reaction product by utilizing the 5'-3' exonoclease to thermos aquaticus DNA polymerase. Proc Natl Acd Sci USA.1991;88(16): 7276-7296.
[6] Heid CA, Stevens J, Livak KJ, et al. Real time quantitative PCR. Genome Res. 1996;6(10): 986-994.
[7] Dotti CG, Sullivan CA., Banker GA. The establishment of polarity by hippocampal neurons in culture. J. Neurosci. 1988;8(4): 1454-1468.
[8] Barnes AP, Polleux F. Establishment of Axon-Dendrite Polarity in Developing Neurons.: Annu Rev Neurosci. 2009 Mar 24. [Epub ahead of print]
[9] Barnes AP, Solecki D, Polleux F. New insights into the molecular mechanisms specifying neuronal polarity in vivo. Curr Opin Neurobiol. 2008 Feb;18(1):44-52.
[10] Dotti CG, Banker GA. Experimentally induced alteration in the polarity of developing neurons. Nature. 1987;330(6145): 254-256.
[1 l]Dajas-Bailador F, Jones EV, Whitmarsh AJ. The JIP1 scaffold protein regulates axonal development in cortical neurons. J Pharmacol Sci. 2003;91(4):267-270.
[12] Setou M, Hayasaka T, Yao I. Axonal transport versus dendritic transport. J Neurobiol. 2004;58(2):201-206.
[13]Skene JH. Axonal Growth-Associated Proteins. Annu Rev neurosci. 1989; 12: 127-156.
[14]Xu JJ, Chen EY, Lu CL, et al. Recombinant ciliary neurotrophic factor promotes nerve regeneration and induces gene expression in silicon tube-bridged transected sciatic nerves in adult rats. J Clin Neurosci. 2009;16(6):812-817.
[15]Larsen MH, Hay-Schmidt A, Ronn LC, et al. Temporal expression of brain-derived neurotrophic factor (BDNF) mRNA in the rat hippocampus after treatment with selective and mixed monoaminergic antidepressants. Eur J Pharmacol. 2008;578(2-3):114-122.
[16] Aigner L, Arber S, Kapfhammer JP, et al. Overexpression of the neural growth-associated protein GAP-43 induces nerve sprouting in the adult nervous system of transgenic mice. Cell.1995;83:269 -278.
[17]Tsai SY, Yang LY, Wu CH, et al. Injury-induced Janus kinase/protein kinase C-dependent phosphorylation of growth-associated protein 43 and signal transducer and activator of transcription 3 for neurite growth in dorsal root ganglion. J Neurosci Res. 2007;85(2):321-231.
[18]Teng FY, Tang BL. Axonal regeneration in adult CNS neurons-signaling molecules and pathways. J Neurochem. 2006;96(6):1501-8. Epub 2006 Feb 10.
[19]BenowitzL I, Routtenberg A. GAP243: an intrinsic determinant of neuronal development and plasticity. Trends Neurosci. 1997; 20: 84 - 91.
[20] Liu D, McIlvain HB, Fennell M, et al. Screening of immunophilin ligands by quantitative analysis of neurofilament expression and neurite outgrowth in cultured neurons and cells. J NeurosciMeth. 2007; 163:310 - 320.
[21]Costantini LC, Isacson O. Immunophilin ligands and GDNF enhance neurite branching or elongation from developing dopamine neurons in culture. Exp Neurol. 2000;164(1):60-70.
[22]Uchida A, Brown A .Arrival, reversal and departure of neurofilament at the tips of growing axons. Mol Biol Cell.2004;15(9): 4215-4225.
[23]Zhang G, Jin LQ, Sul JY, et al. Live imaging of regenerating lamprey spinal axons. Neurorehabil Neural Repair. 2005;19(1):46-57.
[24] Whitmarsh AJ, Cavanagh J, Tournier C, et al. A mammalian scaffold complex that selectively mediates MAP kinase activation. Science.1998;281(5383): 1671-1674.
[25]Ikeda A, Hasegawa K, Masaki M, et al. Mixed lineage kinase LZK forms a functional signaling complex with JIP-1, a scaffold protein of the c-Jun NH(2)-terminal kinase pathway. J Biochem. 2001 Dec;130(6):773-781.
[26]Yasuda J, Whitmarsh AJ, Cavanagh J, et al. The JIP group of mitogen-activated protein kinase scaffold proteins. Mol Cell Biol. 1999;19(10):7245-7254.
1. Greene LA and Tischler AS,Establishment of a noradrenergic clonal cell line of rat adrenal pheochromocytoma cells that respond to nerve growth factor. Proc Nat Acad Sci. 1976;73: 2424-2428.
2. McFarlane EH, Dawe GS, Marks M, Campbell IC. Changes in neurite outgrowth but not in cell division induced by low EMF exposure: influence of field strength and culture conditions on responses in rat PC12 pheochromocytoma " cells. Bioelectrochemistry. 2000;52(l):23-28.
3. Mien JP,Mushynski WE. Neurofilaments in health and disease. Prog Nucleic Acid Res Mol Biol.1998;61:1-23.
4. Gotow T. Neurofilaments in health and disease.Med Electron Microsc.2000;33(4):173-199.
5. Tsang YM, Chiong F, Kuznetsov D, Kasarskis E, Geula C. Motor neurons are rich in non-phosphorylated neurofilaments: cross-species comparison and alterations in ALS. Brain Res. 2000;861(l):45-58.
6. Whitmarsh AJ,Cavanagh J,Tournier C, et al. A mammalian scaffold complex that selectively mediates MAP kinase activation. Science. 1998;281(5383): 1671-1674.
7. Ikeda A, Hasegawa K, Masaki M, et al. Mixed lineage kinase LZK forms a functional signaling complex with JIP-1, a scaffold protein of the c-Jun NH(2)-terminal kinase pathway. J Biochem. 2001 Dec;130(6):773-781.
8. Klesse LJ,Meyers KA,Marshall CJ,et al. Nerve growth factor induces survival and differentiation through two distinct signaling cascades in PC12 cells. Oncogene. 1999; 18:2055-2068.
9. Sun P, Watanabe H, Takano K. Sustained activation of M-Ras induced by nerve growth factor is essential for neuronal differentiation of PC12 cells. Genes Cells. 2006; 11 (9): 1097-1113.
10. Agell N, Bachs O, Rocamora N, Villalonga P. Modulation of the Ras/Raf/MEK/ERK pathway by Ca(2+), and calmodulin. Cell Signal. 2002;14(8):649-654.
11. Wooten MW, Seibenhener ML, Neidigh KB, et al. Mapping of atypical protein kinase C within the nerve growth factor signaling cascade: relationship to differentiation and survival of PC12 cells. Mol Cell Biol. 2000;20(13):4494-4504.
12. Tong L,Perez-Polo JR. Effect of nerve growth factor on AP-l,NF-Kappa B,and Oct DNA-binding activity in apoptotic PC12 cells: extrinsic and intrinsic elements. J Neurosci Res.1996;45(1): 1-12.
13. Groot M, Boxer LM, Thiel G. Nerve growth factor- and epidermal growth factor-regulated gene transcription in PC12 pheochromocytoma and INS-1 insulinoma cells. Eur J Cell Biol. 2000;79(12):924-935.
14. Lambeng N, Michel PP, Brugg B, et al. Mechanisms of apoptosis in PC12 cells irreversibly differentiated with nerve growth factor and cyclic AMP. Brain Res. 1999;821(1):60-68.
15. Gutacker C, Klock G, Diel P, et al. Nerve growth factor and epidermal growth factor stimulate clusterin gene expression in PC12 cells. Biochem J. 1999;339 ( Pt 3):759-766.
[1]Edgar D,Barde YA,Thoenen H.Subpopulations of cultured chick sympathetic neurones differ in their requirements for survival factors.Nature.1981,289(5795):294-295.
[2]Sendtner M,Holtmann B,Kolbeck R,Thoenen H,Barde YA.Brain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nerve section.Nature,1992,360(6404):757-759;
[3]Sendtner M,kreutzberg GW,Thoenen H.Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy.Nature,1990,345(6274):440-441;
[4]Reynolds ML,Woolf CJ.Reciprocal Schwann cell-axon interactions.Curr Opin Neurobiol.1993,3(5),683-693;
[5]Simon M,Porter R,Brown R,Coulton GR,Terenghi G.Effects of NT-4 and BDNF delivery to damaged sciatic nerves on phenotypic recovery of fast and slow muscles fibres.Eur J Neurosci.2003,18(9):2460-2466;
[6]Inserra MM,Bloch DA,Terris D J,Functional indices for sciatic,peroneal,and posterior tibial nerve lesions in the mouse,Microsurgery.1998,18:119-124.
[7]Islamov RR,Hendricks WA,Jones RJ,et al.17b-Estradiol stimulates regeneration of sciatic nerve in female mice,Brain Res.2002,943:283-286.
[8]Roglio I,Bianchi R,Gotti S,et al.Pesaresi,D.Caruso,G.C.Panzica,R.C.Meicangi,Neuroprotective effects of dihydroprogesterone and progesterone in an experimental model of nerve crush injury,Neuroscience.2008,155:673-685.
[9]Boyd JG,Gordon T.Glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor sustain the axonal regeneration of chronically axotomized motoneurons in vivo,Exp.Neurol.2003,183:610-6191
[10] Terenghi G. Peripheral nerve regeneration and neurotrophic factors. J. Anat. 1999,194: 1-14.
[11] Gordon T, Sulaiman O, Boyd JG. Experimental strategies to promote functional recovery after peripheral nerve injuries. J. Peripher. Nerv. Syst. 2003, 8: 236-250.
[12] Fu SY, Gordon T. Contributing factors to poor functional recovery after delayed nerve repair: prolonged axotomy, J. Neurosci. 1995,15: 3876-3885.
[13] Fu SY, Gordon T. The cellular and molecular basis of peripheral nerve regeneration, Mol. Neurobiol. 1997,14: 67-116.
[14] Oliveira EF, Mazzer N, Barbieri CH, et al. Correlation between functional index and morphometry to evaluate recovery of the rat sciatic nerve following crush injury: experimental study. J Reconstr Microsurg. 2001,17: 69-75.
[15]Raso VV, Barbieri CH, Mazzer N, et al. Can therapeutic ultrasound influence the regeneration of peripheral nerves? J. Neurosci. Methods. 2005,142: 185-192.
[16] Mazzer PY, Barbieri CH, Mazzer N, et al. Morphologic and morphometric evaluation of experimental acute crush injuries of the sciatic nerve of rats. J. Neurosci. Methods. 2008, 173: 249-258.
[17] Ide C. Peripheral nerve regeneration, Neurosci. Res. 1996,25: 101-121.
[18] Stoll G, Muller HW. Nerve injury, axonal degeneration and neural regeneration: basic insights. Brain Pathol. 1999, 9: 313-325.
[19] Committee of National Pharmacopoeia, Pharmacopoeia of the People's Republic of China, Chemical Industry Press, Beijing (2005) 49.
[20] Sakakima H, Yoshida Y, Morimoto N. The effect of denervation and subsequent reinnervation on the morphology of rat soleus muscels. J. Phys. Ther. Sci. 2002, 14: 21-26.
[21] Batt J, Bain J, Goncalves J. Differential gene expression profiling of short and long term denervated muscle. FASEB J. 2006, 20:115-117.
[22] Eisenberg HA, Hood DA. Blood flow, mitochondria, and performance in skeletal muscle after denervation and reinnervation, J. Appl. Physiol. 1994, 76: 859-866.
[23] White KK, Vaughan DW. Age effects on cytochrome oxidase activities during denervation and recovery of three muscle fiber types. Anat. Rec. 1991,230: 460-467.
1. Fry EJ, Ho C, David S. A role for Nogo receptor in macrophage clearance from injured peripheral nerve. Neuron. 2007;53(5):649-662.
2. Hirata K, Kawabuchi M. Myelin phagocytosis by macrophages and nonmacrophages during Wallerian degeneration. Microsc Res Tech. 2002 6;57(6):541-547.
3. Pu LL, Syed SA, Reid M, et al. Effects of nerve growth factor on nerve regeneration through a vein graft across a gap. Plast Reconstr Surg. 1999;104(5):1379-1385.
4. Reynolds ML, Woolf CJ. Reciprocal Schwann cell-axon interactions. Curr Opin Neurobiol. 1993;3(5):683-693.
5. Berthold CH, Nilsson RI. De- and remyelination in spinal roots during normal perinatal development in the cat: a brief summary of structural observations and a conceptual hypothesis. J Anat. 2002;200(4):391-403.
6. Son YJ, Thompson WJ. Schwann cell processes guide regeneration of peripheral axons. Neuron. 1995;14(1):125-132.
7. Hall S. Axonal regeneration through acellular muscle grafts. J Anat. 1997; 190:57-71.
8. Murphy RA, Acheson A, Hodges R, et al. Immunological relationships of NGF, BDNF, and NT-3: recognition and functional inhibition by antibodies to NGF. J Neurosci. 1993;13(7):2853-2862.
9. Terenghi G, Calder JS, Birch R, et al. A morphological study of Schwann cells and axonal regeneration in chronically transected human peripheral nerves. Journal of Hand Surgery. 1998;23(5):583-587.
10. Terris DJ, Fee WE Jr. Current issues in nerve repair. Arch Otolaryngol Head Neck Surg. 1993; 119(7):725-731.
11. Brushart TM. Motor axons preferentially reinnervate motor pathways. J Neurosci. 1993;13(6):2730-2738.
12. Skaper SD, Moore SE, Walsh FS. Cell signalling cascades regulating neuronal growth-promoting and inhibitory cues. Prog Neurobiol. 2001;65(6):593-608.
13. Edelman GM, Jones FS. Gene regulation of cell adhesion: a key step in neural morphogenesis. Brain Res Brain Res Rev. 1998;26(2-3):337-352.
14. Saad B, Constam DB, Ortmann R, et al. Astrocyte-derived TGF-beta 2 and NGF differentially regulate neural recognition molecule expression by cultured astrocytes. J Cell Biol. 1991 ;115(2):473-484.
15. Gu X, Thomas PK, King RH. Chemotropism in nerve regeneration studied in tissue culture. J Anat. 1995;186:153-163.
16. Madison RD, Robinson GA, Chadaram SR. The specificity of motor neurone regeneration (preferential reinnervation). Acta Physiol (Oxf). 2007; 189(2):201-206.
17. Madison RD, Archibald SJ, Brushart TM. Reinnervation accuracy of the rat femoral nerve by motor and sensory neurons. J Neurosci. 1996; 16(18):5698—5703.
18. Terzis JK, Smith KL. Repair and grafting of the peripheral nerve. In General Principles of Plastic Surgery (ed.McCarthy JG).1990: 630-697.
19. Hirata K, Kawabuchi M. Myelin phagocytosis by macrophages and nonmacrophages during Wallerian degeneration. Microsc Res Tech. 2002, 57: 541-547.
20. Chen ZL, Yu WM, Strickland S. Peripheral regeneration. Ann Rev Neurosci. 2007, 30: 209-233.
21. Scherer SS, Salzer JL. Axon-Schwann cell interactions during peripheral nerve degenerationand regeneraion. Oxford University Press, Oxford, 2001,299-330.
22. Hopkins SJ, Rothwell NJ. Cytokines and the nervous system. I: Expression and recognition. Trends Neurosci. 1995;18(2):83-88.
23. Kurihara H, Shinohara H, Yoshino H, et al. Neurotrophins in cultured cells from periodontal tissues. J Periodontol. 2003;74(1):76-84.
24. Davies AM. The neurotrophic hypothesis: where does it stand? Philos Trans R Soc Lond B Biol Sci. 1996;351(1338):389-394.
25. Rossi J, Airaksinen MS. GDNF family signalling in exocrine tissues: distinct roles for GDNF and neurturin in parasympathetic neuron development. Adv Exp Med Biol. 2002;506(Pt A):19-26.
26. Anand P, Terenghi G, Warner G, et al. The role of endogenous nerve growth factor in human diabetic neuropathy. Nat Med. 1996;2(6):703-707.
27. Hiltunen JO, Laurikainen A, Klinge E, et al.Neurotrophin-3 is a target-derived neurotrophic factor for penile erection-inducing neurons. Neuroscience. 2005;133(1):51-58.
28. Berkemeier LR, Winslow JW, Kaplan DR, et al. Neurotrophin-5: a novel neurotrophic factor that activates trk and trkB. Neuron. 1991 ;7(5):857—866.
29. Hallbook F, Ibanez CF, Persson H. Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary. Neuron. 1991;6(5):845-858.
30. Rodriguez-Tebar A, Dechant G, Gotz R, et al. Binding of neurotrophin-3 to its neuronal receptors and interactions with nerve growth factor and brain-derived neurotrophic factor. EMBO J. 1992; 11(3):917-922.
31. Chao MV, Hempstead BL. p75 and Trk: a two-receptor system. Trends Neurosci. 1995;18(7):321-326.
32. Gargano N, Levi A, Alema S. Modulation of nerve growth factor internalization by direct interaction between p75 and TrkA receptors. J Neurosci Res. 1997;50(1):1-12.
33. Anneren C, Lindholm CK, Kriz V, et al.The FRK/RAK-SHB signaling cascade: a versatile signal-transduction pathway that regulates cell survival, differentiation and proliferation.Curr Mol Med. 2003;3(4):313-324.
34. Klein R, Lamballe F, Bryant S, et al. The trkB tyrosine protein kinase is a receptor for neurotrophin-4. Neuron. 1992;8(5):947-956.
35. Davies AM, Minichiello L, Klein R. Developmental changes in NT3 signalling via TrkA and TrkB in embryonic neurons. EMBO J. 1995;14(18):4482-4489.
36. Ryden M, Ibanez CF. Binding of neurotrophin-3 to p75LNGFR, TrkA, and TrkB mediated by a single functional epitope distinct from that recognized by trkC. J Biol Chem. 1996;271(10):5623-5627.
37. Wright DE, Snider WD. Neurotrophin receptor mRNA expression defines distinct populations of neurons in rat dorsal root ganglia. J Comp Neurol. 1995;351(3):329-338.
38. Bennett DL, Dmietrieva N, Priestley JV, et al. TrkA, CGRP and IB4 expression in retrogradely labelled cutaneous and visceral primary sensory neurones in the rat. Neurosci Lett. 1996;206(1):33-36.
39. Davis-Lopez de Carrizosa MA, Morado-Diaz CJ, Tena JJ, et al. Complementary actions of BDNF and neurotrophin-3 on the firing patterns and synaptic composition of motoneurons. J Neurosci. 2009;29(2):575-587
40. Yoshizaki K, Yamamoto S, Yamada A, et al.Neurotrophic factor neurotrophin-4 regulates ameloblastin expression via full-length TrkB.J Biol Chem. 2008;283(6):3385-91.
41. Griesbeck O, Parsadanian AS, Sendtner M, et al. Expression of neurotrophins in skeletal muscle: quantitative comparison and significance for motoneuron survival and maintenance of function. J Neurosci Res. 1995;42(1):21-33.
42. Wood TK, McDermott KW, Sullivan AM. Differential effects of growth/differentiation factor 5 and glial cell line-derived neurotrophic factor on dopaminergic neurons and astroglia in cultures of embryonic rat midbrain. J Neurosci Res. 2005;80(6):759-766.
43. Baloh RH, Tansey MG, Golden JP, et al. TrnR2, a novel receptor that mediates neurturin and GDNF signaling through Ret. Neuron. 1997;18(5):793-802.
44. Bennett DL, Michael GJ, Ramachandran N, et al. A distinct subgroup of small DRG cells express GDNF receptor components and GDNF is protective for these neurons after nerve injury. J Neurosci. 1998;18(8):3059-3072.
45. Matheson CR, Wang J, Collins FD, et al. Long-term survival effects of GDNF on neonatal rat facial motoneurons after axotomy. Neuroreport. 1997;8(7): 1739—1742.
46. Park K, Luo JM, Hisheh S, et al.Cellular mechanisms associated with spontaneous and ciliary neurotrophic factor-cAMP-induced survival and axonal regeneration of adult retinal ganglion cells.J Neurosci. 2004;24(48):10806-10815.
47. Richardson PM. Ciliary neurotrophic factor: a review. Pharmacol Ther. 1994;63(2): 187-198.
48. Rende M, Muir D, Ruoslahti E, et al. Immunolocalization of ciliary neuronotrophic factor in adult rat sciatic nerve. Glia. 1992;5(1):25-32.
49. Helgren ME, Squinto SP, Davis HL, et al. Trophic effect of ciliary neurotrophic factor on denervated skeletal muscle. Cell. 1994;76(3):493-504.
50. Macosko JC, Newbern JM, Rockford J, et al.Fewer active motors per vesicle may explain slowed vesicle transport in chick motoneurons after three days in vitro.Brain Res. 2008;1211:6-12.
51. Adler R. Ciliary neurotrophic factor as an injury factor. Curr Opin Neurobiol. 1993;3(5):785-789.
52. Yamamori T, Fukada K, Aebersold R, et al. The cholinergic neuronal differentiation factor from heart cells is identical to leukemia inhibitory factor. Science. 1989;246(4936):1412-1416.
53. Thompson SW, Vernallis AB, Heath JK, et al. Leukaemia inhibitory factor is retrogradely transported by a distinct population of adult rat sensory neurons: co-localization with trkA and other neurochemical markers. Eur J Neurosci. 1997;9(6):1244-1251.
54. Michael GJ, Averill S, Nitkunan A, et al. Nerve growth factor treatment increases brain-derived neurotrophic factor selectively in TrkA-expressing dorsal root ganglion cells and in their central terminations within the spinal cord. J Neurosci. 1997; 17(21):8476-8490.
55. Carraway KL, 3rd, Burden SJ. Neuregulins and their receptors. Curr Opin Neurobiol. 1995;5(5):606-612.
56. Chen MS, Bermingham-McDonogh O, Danehy FT, et al. Expression of multiple neuregulin transcripts in postnatal rat brains. J Comp Neurol. 1994;349(3):389-400.
57. Dong Z, Brennan A, Liu N, et al. Neu differentiation factor is a neuron-glia signal and regulates survival, proliferation, and maturation of rat Schwann cell precursors. Neuron. 1995;15(3):585-596.
58. Trachtenberg JT, Thompson WJ. Schwann cell apoptosis at developing neuromuscular junctions is regulated by glial growth factor. Nature. 1996;379(6561):174—177.
59. Castro C, Kuffler DP. Membrane-bound CSPG mediates growth cone outgrowth and substrate specificity by Schwann cell contact with the DRG neuron cell body and not via growth cone contact.Exp Neurol. 2006;200(1):19-25.
60. Oakley RA, Garner AS, Large TH, et al. Muscle sensory neurons require neurotrophin-3 from peripheral tissues during the period of normal cell death. Development. 1995;121(5):1341-1350.
61. Rush RA, Chie E, Liu D, et al. Neurotrophic factors are required by mature sympathetic neurons for survival, transmission and connectivity. Clin Exp Pharmacol Physiol. 1997;24(8):549-555.
62. Molliver DC, Wright DE, Leitner ML, et al. IB4-binding DRG neurons switch from NGF to GDNF dependence in early postnatal life. Neuron. 1997;19(4):849-861.
63. Jivan S, Novikova LN, Wiberg M, et al. The effects of delayed nerve repair on neuronal survival and axonal regeneration after seventh cervical spinal nerve axotomy in adult rats. Exp Brain Res. 2006;170(2):245-254.
64. Groves MJ, Christopherson T, Giometto B, et al. Axotomy-induced apoptosis in adult rat primary sensory neurons. J Neurocytol. 1997;26(9):615-624.
65. Krekoski CA, Parhad IM, Clark AW. Attenuation and recovery of nerve growth factor receptor mRNA in dorsal root ganglion neurons following axotomy. J Neurosci Res. 1996, 43(1): 1-11.
66. Verge VM, Gratto KA, Karchewski LA, et al. Neurotrophins and nerve injury in the adult. Philos Trans R Soc Lond B Biol Sci. 1996;351(1338):423-430.
67. Munson JB, Shelton DL, McMahon SB. Adult mammalian sensory and motor neurons: roles of endogenous neurotrophins and rescue by exogenous neurotrophins after axotomy. J Neurosci. 1997;17(1):470-476.
68. Anand P, Terenghi G, Birch R, et al. Endogenous NGF and CNTF levels in human peripheral nerve injury. Neuroreport. 1997;8(8):1935-1938.
69. Robertson MD, Toews AD, Bouldin TW, et al. NGFR-mRNA expression in sciatic nerve: a sensitive indicator of early stages of axonopathy. Brain Res Mol Brain Res. 1995;28(2):231-238.
70. Anton ES, Weskamp G, Reichardt LF, et al. Nerve growth factor and its low-affinity receptor promote Schwann cell migration. Proc Natl Acad Sci U S A. 1994;91(7):2795-2799.
71. Thippeswamy T, Howard MR, Cosgrave AS, et al.Nitric oxide-NGF mediated PPTA/SP, ADNP, and VIP expression in the peripheral nervous system.J Mol Neurosci. 2007;33(3):268-277.
72. Shadiack AM, Sun Y, Zigmond RE. Nerve growth factor antiserum induces axotomy-like changes in neuropeptide expression in intact sympathetic and sensory neurons. J Neurosci. 2001;21(2):363-371.
73. Zhang X, Ji RR, Nilsson S, et al. Neuropeptide Y and galanin binding sites in rat and monkey lumbar dorsal root ganglia and spinal cord and effect of peripheral axotomy. Eur J Neurosci. 1995;7(3):367-380.
74. Wakisaka S, Takikita S, Youn SH, et al. Partial coexistence of neuropeptide Y and calbindin D28k in the trigeminal ganglion following peripheral axotomy of the inferior alveolar nerve in the rat. Brain Res. 1996;707(2):228-234.
75. Mulderry PK. Neuropeptide expression by newborn and adult rat sensory neurons in culture: effects of nerve growth factor and other neurotrophic factors. Neuroscience. 1994;59(3):673-688.
76. Kerekes N, Landry M, Rydh-Rinder M, et al. The effect of NGF, BDNF and bFGF on expression of galanin in cultured rat dorsal root ganglia. Brain Res. 1997;754(1-2):131-141.
77. Bucelli RC, Gonsiorek EA, Kim WY, et al.Statins decrease expression of the proinflammatory neuropeptides calcitonin gene-related peptide and substance P in sensory neurons. J Pharmacol Exp Ther. 2008;324(3): 1172-1180.
78. Ohara S, Tantuwaya V, DiStefano PS, et al. Exogenous NT-3 mitigates the transganglionic neuropeptide Y response to sciatic nerve injury. Brain Res. 1995;699(1):143-148.
79. Thompsons WN,Priestley JV,Southalla. gp130 cytokines, leukaemia inhibitory factor and interleukin-6 induce neuropeptide expression in intact adult rat sensory neurons in vivo:time-course, specificity and comparison with sciatic nerve axotomy. Neuroscience.1998;84:1247-1255.
80. Cho HJ, Kim SY, Park MJ, et al. Expression of mRNA for brain-derived neurotrophic factor in the dorsal root ganglion following peripheral inflammation. Brain Res. 1997;749(2):358-362.
81. Zhou XF, Li WP, Zhou FH, et al. Differential effects of endogenous brain-derived neurotrophic factor on the survival of axotomized sensory neurons in dorsal root ganglia: a possible role for the p75 neurotrophin receptor. Neuroscience. 2005;132(3):591-603.
82. Kashiba H, Ueda Y, Ueyama T, et al. Relationship between BDNF- and trk-expressing neurones in rat dorsal root ganglion: an analysis by in situ hybridization. Neuroreport. 1997;8(5):1229-1234.
83. Skoff AM, Adler JE. Nerve growth factor regulates substance P in adult sensory neurons through both TrkA and p75 receptors.Exp Neurol. 2006;197(2):430-436.
84. Zhou XF, Rush RA. Endogenous brain-derived neurotrophic factor is anterogradely transported in primary sensory neurons. Neuroscience. 1996;74(4):945—953.
85. James R, Tonra JR, Curts R, et al. Axotomy upregulates the anterograde transport and expression of brain derived neurotrophic factor in sensory neurons. Journal of Neuroscience.1998;18:4371-4383.
86. Carroll SL, Miller ML, Frohnert PW, et al. Expression of neuregulins and their putative receptors, ErbB2 and ErbB3, is induced during Wallerian degeneration. J Neurosci. 1997;17(5):1642-1659.
87. Kuo LT, Groves MJ, Scaravilli F, et al. Neurotrophin-3 administration alters neurotrophin, neurotrophin receptor and nestin mRNA expression in rat dorsal root ganglia following axotomy .Neuroscience. 2007;147(2):491-507.
88. Rende M, Provenzano C, Tonali P. Modulation of low-affinity nerve growth factor receptor in injured, adult rat spinal cord motoneurons. J Comp Neurol. 1993 ;338(4):560-574.
89. Rende M, Provenzano C, Stipa G, et al. Effects of sciatic nerve grafts on choline acetyltransferase and p75 expression in transected adult hypoglossal motoneurons. Neuroscience. 1997;81(2):517-525.
90. Yan Q, Elliott J, Snider WD. Brain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death. Nature. 1992;360(6406):753-755.
91. Novikova L, Novikov L, Kellerth JO. Effects of neurotransplants and BDNF on the survival and regeneration of injured adult spinal motoneurons. Eur J Neurosci. 1997;9(12):2774-2777.
92. Kishino A, Ishige Y, Tatsuno T, et al.BDNF prevents and reverses adult rat motor neuron degeneration and induces axonal outgrowth. Exp Neurol. 1997;144(2):273-286.
93. Kasahara K, Nakagawa T, Kubota T. Neuronal loss and expression of neurotrophic factors in a model of rat chronic compressive spinal cord injury. Spine. 2006;31(18):2059-2066.
94. Sendtner M, Gotz R, Holtmann B, et al. Endogenous ciliary neurotrophic factor is a lesion factor for axotomized motoneurons in adult mice. J Neurosci. 1997;17(18):6999-7006.
95. Hiruma S, Shimizu T, Huruta T, et al. Ciliary neurotrophic factor immunoreactivity in rat intramuscular nerve during reinnervation through a silicone tube after severing of the rat sciatic nerve. Exp Mol Pathol. 1997;64(1):23-30.
96. Newman JP, Verity AN, Hawatmeh S, et al. Ciliary neurotrophic factors enhances peripheral nerve regeneration. Arch Otolaryngol Head Neck Surg. 1996;122(4):399-403.
97. Zhang J, Lineaweaver WC, Oswald T, et al. Ciliary neurotrophic factor for acceleration of peripheral nerve regeneration: an experimental study. J Reconstr Microsurg. 2004;20(4):323-327.
98. Curtis R, Scherer SS, Somogyi R, et al. Retrograde axonal transport of LIF is increased by peripheral nerve injury: correlation with increased LIF expression in distal nerve. Neuron. 1994; 12(1):191—204.
99. Matsuoka I, Nakane A, Kurihara K. Induction of LIF-mRNA by TGF-beta 1 in Schwann cells. Brain Res. 1997;776(1-2):170-180.
100.Tham S, Dowsing B, Finkelstein D, et al. Leukemia inhibitory factor enhances the regeneration of transected rat sciatic nerve and the function of reinnervated muscle. J Neurosci Res. 1997;47(2):208-215.
101.White JD, Davies M, Grounds MD. Leukaemia inhibitory factor increases myoblast replication and survival and affects extracellular matrix production: combined in vivo and in vitro studies in post-natal skeletal muscle. Cell Tissue Res. 2001;306(1):129-141.
102.Tessarollo L, Vogel KS, Palko ME, et al. Targeted mutation in the neurotrophin-3 gene results in loss of muscle sensory neurons. Proc Natl Acad Sci U S A. 1994;91(25):11844-11848.
103.Oakley RA, Lefcort FB, Clary DO, et al. Neurotrophin-3 promotes the differentiation of muscle spindle afferents in the absence of peripheral targets. J Neurosci. 1997;17(11):4262-4274.
104.Chen J, Qi JG, Zhang W, et al.Electro-acupuncture induced NGF, BDNF and NT-3 expression in spared L6 dorsal root ganglion in cats subjected to removal of adjacent ganglia.Neurosci Res. 2007;59(4):399-405.
105.Sterne GD, Coulton GR, Brown RA, et al. Neurotrophin-3-enhanced nerve regeneration selectively improves recovery of muscle fibers expressing myosin heavy chains 2b. J Cell Biol. 1997;139(3):709-715.
106.Chan JR, Cosgaya JM, Wu YJ, et al. Neurotrophins are key mediators of the myelination program in the peripheral nervous system. Proc Natl Acad Sci USA. 2001, 98: 14661-14668.
107.Yan Q, Matheson C, Lopez OT. In vivo neurotrophic effects of GDNF on neonatal and adult facial motor neurons. Nature. 1995;373(6512):341-344.
108.Nguyen QT, Parsadanian AS, Snider WD, et al. Hyperinnervation of neuromuscular junctions caused by GDNF overexpression in muscle. Science. 1998;279(5357): 1725-1729.
109.Hoke A, Gordon T, Zochodne DW, et al. A decline in glial cell-line-derived neurotrophic factor expression is associated with impaired regeneration after long-term Schwann cell denervation. Exp Neurol. 2002;173(1):77-85.
110.Naveilhan P, ElShamy WM, Ernfors P. Differential regulation of mRNAs for GDNF and its receptors Ret and GDNFR alpha after sciatic nerve lesion in the mouse. Eur J Neurosci. 1997;9(7): 1450-1460.
111.Mendell LM. Neurotrophins and sensory neurons: role in development, maintenance and injury. A thematic summary. Philos Trans R Soc Lond B Biol Sci. 1996;351(1338):463-467.
112.Whitworth IH, Brown RA, Dore CJ, et al. Nerve growth factor enhances nerve regeneration through fibronectin grafts. J Hand Surg [Br]. 1996;21(4):514-522.
113. Jivan S, Novikova LN, Wiberg M, et al.The effects of delayed nerve repair on neuronal survival and axonal regeneration after seventh cervical spinal nerve axotomy in adult rats. Exp Brain Res. 2006 ;170(2):245-254.
114.Gold BG. Axonal regeneration of sensory nerves is delayed by continuous intrathecal infusion of nerve growth factor. Neuroscience. 1997;76(4):1153-1158.
115.Zhu QT, Zhu JK, Chen GY. Location of collateral sprouting of donor nerve following end-to-side neurorrhaphy.Muscle Nerve. 2008;38(5): 1506-1509.
116.Sterne GD, Brown RA, Green CJ, et al. Neurotrophin-3 delivered locally via fibronectin mats enhances peripheral nerve regeneration. Eur J Neurosci. 1997;9(7):1388-1396.
117.Munson JB, McMahon SB. Effects of GDNF on axotomized sensory and motor neurons in adult rats. Eur J Neurosci. 1997;9(6):1126-1129.
118.Helgren ME, Cliffer KD, Torrento K, et al. Neurotrophin-3 administration attenuates deficits of pyridoxine-induced large-fiber sensory neuropathy. J Neurosci. 1997; 17(1): 372-382.
119.Lewin SL, Utley DS, Cheng ET, et al. Simultaneous treatment with BDNF and CNTF after peripheral nerve transection and repair enhances rate of functional recovery compared with BDNF treatment alone. Laryngoscope. 1997;107(7):992-999.
120.Papakostas I, Mourouzis I, Mourouzis K, et al. Functional effects of local thyroid hormone administration after sciatic nerve injury in rats.Microsurgery. 2009;29(1):35-41.
121.Subang MC, Bisby MA, Richardson PM. Delay of CNTF decrease following peripheral nerve injury in C57BL/WW mice. J Neurosci Res. 1997;49(5):563-568.
122.You S, Petrov T, Chung PH, et al. The expression of the low affinity nerve growth factor receptor in long-term denervated Schwann cells. Glia. 1997;20(2):87-100.
123.McAllister AK, Katz LC, Lo DC. Opposing roles for endogenous BDNF and NT-3 in regulating cortical dendritic growth. Neuron. 1997;18(5):767-778.
124.Roehm PC, Hansen MR. Strategies to preserve or regenerate spiral ganglion neurons. Curr Opin Otolaryngol Head Neck Surg. 2005;13(5):294-300.
125.Arce V, Pollock RA, Philippe JM, et al. Synergistic effects of schwann- and muscle-derived factors on motoneuron survival involve GDNF and cardiotrophin-1 (CT-1). J Neurosci. 1998;18(4):1440-1448.
126.Lindsay RM. Therapeutic potential of the neurotrophins and neurotrophin-CNTF combinations in peripheral neuropathies and motor neuron diseases. Ciba Found Symp. 1996;196:39-53.
127.Hoffer B, Olson L. Treatment strategies for neurodegenerative diseases based on trophic factors and cell transplantation techniques. J Neural Transm Suppl. 1997;49:l-10.
128.Strand AD, Baquet ZC, Aragaki AK, et al.Expression profiling of Huntington's disease models suggests that brain-derived neurotrophic factor depletion plays a major role in striatal degeneration.J Neurosci. 2007;27(43):11758-11768.
[2]Lee SK,Wolfe SW.Peripheral nerve injury and repair.J Am Acad Orthop Surg.2000,8(4):243-252.
[3]Terenghi G.Peripheral nerve regeneration and neurotrophic factors.J.Anat.1999,194(pt 1):1-14.
[4]Schmidt CE,Leach JB.Neural tissue engineering:strategies for repair and regeneration.Annu Rev Biomed Eng.2003,5:293-347.
[5]Edgar D,Barde YA,Thoenen H.Subpopulations of cultured chick sympathetic neurones differ in their requirements for survival factors.Nature.1981,289(5795):294-295.
[6]Sendtner M,Holtmann B,Kolbeck R,et al.Brain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nerve section.Nature,1992,360(6404):757-759.
[7]Sendtner M,kreutzberg GW,Thoenen H.Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy.Nature,1990,345(6274):440-441.
[8]Reynolds ML,Woolf CJ.Reciprocal Schwann cell-axon interactions.Curr Opin Neurobiol.1993,3(5),683-693.
[9]Simon M,Porter R,Brown R,et al.Effects of NT-4 and BDNF delivery to damaged sciatic nerves on phenotypic recovery of fast and slow muscles fibres.Eur J Neurosci.2003,18(9):2460-2466.
[10]Romero MI,Rangappa N,Garry MG,et al.Functional regeneration of chronically injured sensory afferents into adult spinal cord after neurotrophin gene therapy.J.Neurosci.2001,21(21):8.408-16.
[11]Winter CG,Saotome Y,Levison Sw,et al.A role for ciliary neurotrophic factor as an inducer of reactive gliosis,the glial response to central nervous system injury.Proc Natl Acad Sci USA.1995,92(13):5865-5869.
[12]Gary Walsh.Biopharmaceuticals:Biochemistry and Biotechnology.John Wiley &Sons,Ltd.2003.
[13]Saklani A,Kutty SK.Plant-derived compounds in clinical trials.Drug Discovery Today.2008,13(3-4):161-71.Epub 2007 Nov 26.
[14]中国药典委员会,《中国药典》2005年版.
[1] Jin M, Guan CB, Jiang YA, et al. Ca2+-dependent regulation of Rho GTPases triggers turning of nerve growth cones. J. Neuroscience.2005;25(9): 2338-2347.
[2] Cheung ZH, Chin WH, Chen Y, et al. Cdk5 is involved in BDNF-stimulated dendritic growth in hippocampal neurons. PLoS Biol. 2007;5(4): e63
[3] Ji Y, Pang PT, Feng L, Lu B. Cyclic AMP controls BDNF-induced TrkB phosphorylation and dendritic spine formation in mature hippocampal neurons. Nat Neurosci. 2005;8(2): 164-172.
[4] Yamada K, Nabeshima T. Brain-derived neurotrophic factor/TrkB signaling in memory processes. J Pharmacol Sci. 2003;91(4):267-270.
[5] Holland PM, Abramson RD, Watson R, et al. Detection of specific polymerase chain reaction product by utilizing the 5'-3' exonoclease to thermos aquaticus DNA polymerase. Proc Natl Acd Sci USA.1991;88(16): 7276-7296.
[6] Heid CA, Stevens J, Livak KJ, et al. Real time quantitative PCR. Genome Res. 1996;6(10): 986-994.
[7] Dotti CG, Sullivan CA., Banker GA. The establishment of polarity by hippocampal neurons in culture. J. Neurosci. 1988;8(4): 1454-1468.
[8] Barnes AP, Polleux F. Establishment of Axon-Dendrite Polarity in Developing Neurons.: Annu Rev Neurosci. 2009 Mar 24. [Epub ahead of print]
[9] Barnes AP, Solecki D, Polleux F. New insights into the molecular mechanisms specifying neuronal polarity in vivo. Curr Opin Neurobiol. 2008 Feb;18(1):44-52.
[10] Dotti CG, Banker GA. Experimentally induced alteration in the polarity of developing neurons. Nature. 1987;330(6145): 254-256.
[1 l]Dajas-Bailador F, Jones EV, Whitmarsh AJ. The JIP1 scaffold protein regulates axonal development in cortical neurons. J Pharmacol Sci. 2003;91(4):267-270.
[12] Setou M, Hayasaka T, Yao I. Axonal transport versus dendritic transport. J Neurobiol. 2004;58(2):201-206.
[13]Skene JH. Axonal Growth-Associated Proteins. Annu Rev neurosci. 1989; 12: 127-156.
[14]Xu JJ, Chen EY, Lu CL, et al. Recombinant ciliary neurotrophic factor promotes nerve regeneration and induces gene expression in silicon tube-bridged transected sciatic nerves in adult rats. J Clin Neurosci. 2009;16(6):812-817.
[15]Larsen MH, Hay-Schmidt A, Ronn LC, et al. Temporal expression of brain-derived neurotrophic factor (BDNF) mRNA in the rat hippocampus after treatment with selective and mixed monoaminergic antidepressants. Eur J Pharmacol. 2008;578(2-3):114-122.
[16] Aigner L, Arber S, Kapfhammer JP, et al. Overexpression of the neural growth-associated protein GAP-43 induces nerve sprouting in the adult nervous system of transgenic mice. Cell.1995;83:269 -278.
[17]Tsai SY, Yang LY, Wu CH, et al. Injury-induced Janus kinase/protein kinase C-dependent phosphorylation of growth-associated protein 43 and signal transducer and activator of transcription 3 for neurite growth in dorsal root ganglion. J Neurosci Res. 2007;85(2):321-231.
[18]Teng FY, Tang BL. Axonal regeneration in adult CNS neurons-signaling molecules and pathways. J Neurochem. 2006;96(6):1501-8. Epub 2006 Feb 10.
[19]BenowitzL I, Routtenberg A. GAP243: an intrinsic determinant of neuronal development and plasticity. Trends Neurosci. 1997; 20: 84 - 91.
[20] Liu D, McIlvain HB, Fennell M, et al. Screening of immunophilin ligands by quantitative analysis of neurofilament expression and neurite outgrowth in cultured neurons and cells. J NeurosciMeth. 2007; 163:310 - 320.
[21]Costantini LC, Isacson O. Immunophilin ligands and GDNF enhance neurite branching or elongation from developing dopamine neurons in culture. Exp Neurol. 2000;164(1):60-70.
[22]Uchida A, Brown A .Arrival, reversal and departure of neurofilament at the tips of growing axons. Mol Biol Cell.2004;15(9): 4215-4225.
[23]Zhang G, Jin LQ, Sul JY, et al. Live imaging of regenerating lamprey spinal axons. Neurorehabil Neural Repair. 2005;19(1):46-57.
[24] Whitmarsh AJ, Cavanagh J, Tournier C, et al. A mammalian scaffold complex that selectively mediates MAP kinase activation. Science.1998;281(5383): 1671-1674.
[25]Ikeda A, Hasegawa K, Masaki M, et al. Mixed lineage kinase LZK forms a functional signaling complex with JIP-1, a scaffold protein of the c-Jun NH(2)-terminal kinase pathway. J Biochem. 2001 Dec;130(6):773-781.
[26]Yasuda J, Whitmarsh AJ, Cavanagh J, et al. The JIP group of mitogen-activated protein kinase scaffold proteins. Mol Cell Biol. 1999;19(10):7245-7254.
1. Greene LA and Tischler AS,Establishment of a noradrenergic clonal cell line of rat adrenal pheochromocytoma cells that respond to nerve growth factor. Proc Nat Acad Sci. 1976;73: 2424-2428.
2. McFarlane EH, Dawe GS, Marks M, Campbell IC. Changes in neurite outgrowth but not in cell division induced by low EMF exposure: influence of field strength and culture conditions on responses in rat PC12 pheochromocytoma " cells. Bioelectrochemistry. 2000;52(l):23-28.
3. Mien JP,Mushynski WE. Neurofilaments in health and disease. Prog Nucleic Acid Res Mol Biol.1998;61:1-23.
4. Gotow T. Neurofilaments in health and disease.Med Electron Microsc.2000;33(4):173-199.
5. Tsang YM, Chiong F, Kuznetsov D, Kasarskis E, Geula C. Motor neurons are rich in non-phosphorylated neurofilaments: cross-species comparison and alterations in ALS. Brain Res. 2000;861(l):45-58.
6. Whitmarsh AJ,Cavanagh J,Tournier C, et al. A mammalian scaffold complex that selectively mediates MAP kinase activation. Science. 1998;281(5383): 1671-1674.
7. Ikeda A, Hasegawa K, Masaki M, et al. Mixed lineage kinase LZK forms a functional signaling complex with JIP-1, a scaffold protein of the c-Jun NH(2)-terminal kinase pathway. J Biochem. 2001 Dec;130(6):773-781.
8. Klesse LJ,Meyers KA,Marshall CJ,et al. Nerve growth factor induces survival and differentiation through two distinct signaling cascades in PC12 cells. Oncogene. 1999; 18:2055-2068.
9. Sun P, Watanabe H, Takano K. Sustained activation of M-Ras induced by nerve growth factor is essential for neuronal differentiation of PC12 cells. Genes Cells. 2006; 11 (9): 1097-1113.
10. Agell N, Bachs O, Rocamora N, Villalonga P. Modulation of the Ras/Raf/MEK/ERK pathway by Ca(2+), and calmodulin. Cell Signal. 2002;14(8):649-654.
11. Wooten MW, Seibenhener ML, Neidigh KB, et al. Mapping of atypical protein kinase C within the nerve growth factor signaling cascade: relationship to differentiation and survival of PC12 cells. Mol Cell Biol. 2000;20(13):4494-4504.
12. Tong L,Perez-Polo JR. Effect of nerve growth factor on AP-l,NF-Kappa B,and Oct DNA-binding activity in apoptotic PC12 cells: extrinsic and intrinsic elements. J Neurosci Res.1996;45(1): 1-12.
13. Groot M, Boxer LM, Thiel G. Nerve growth factor- and epidermal growth factor-regulated gene transcription in PC12 pheochromocytoma and INS-1 insulinoma cells. Eur J Cell Biol. 2000;79(12):924-935.
14. Lambeng N, Michel PP, Brugg B, et al. Mechanisms of apoptosis in PC12 cells irreversibly differentiated with nerve growth factor and cyclic AMP. Brain Res. 1999;821(1):60-68.
15. Gutacker C, Klock G, Diel P, et al. Nerve growth factor and epidermal growth factor stimulate clusterin gene expression in PC12 cells. Biochem J. 1999;339 ( Pt 3):759-766.
[1]Edgar D,Barde YA,Thoenen H.Subpopulations of cultured chick sympathetic neurones differ in their requirements for survival factors.Nature.1981,289(5795):294-295.
[2]Sendtner M,Holtmann B,Kolbeck R,Thoenen H,Barde YA.Brain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nerve section.Nature,1992,360(6404):757-759;
[3]Sendtner M,kreutzberg GW,Thoenen H.Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy.Nature,1990,345(6274):440-441;
[4]Reynolds ML,Woolf CJ.Reciprocal Schwann cell-axon interactions.Curr Opin Neurobiol.1993,3(5),683-693;
[5]Simon M,Porter R,Brown R,Coulton GR,Terenghi G.Effects of NT-4 and BDNF delivery to damaged sciatic nerves on phenotypic recovery of fast and slow muscles fibres.Eur J Neurosci.2003,18(9):2460-2466;
[6]Inserra MM,Bloch DA,Terris D J,Functional indices for sciatic,peroneal,and posterior tibial nerve lesions in the mouse,Microsurgery.1998,18:119-124.
[7]Islamov RR,Hendricks WA,Jones RJ,et al.17b-Estradiol stimulates regeneration of sciatic nerve in female mice,Brain Res.2002,943:283-286.
[8]Roglio I,Bianchi R,Gotti S,et al.Pesaresi,D.Caruso,G.C.Panzica,R.C.Meicangi,Neuroprotective effects of dihydroprogesterone and progesterone in an experimental model of nerve crush injury,Neuroscience.2008,155:673-685.
[9]Boyd JG,Gordon T.Glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor sustain the axonal regeneration of chronically axotomized motoneurons in vivo,Exp.Neurol.2003,183:610-6191
[10] Terenghi G. Peripheral nerve regeneration and neurotrophic factors. J. Anat. 1999,194: 1-14.
[11] Gordon T, Sulaiman O, Boyd JG. Experimental strategies to promote functional recovery after peripheral nerve injuries. J. Peripher. Nerv. Syst. 2003, 8: 236-250.
[12] Fu SY, Gordon T. Contributing factors to poor functional recovery after delayed nerve repair: prolonged axotomy, J. Neurosci. 1995,15: 3876-3885.
[13] Fu SY, Gordon T. The cellular and molecular basis of peripheral nerve regeneration, Mol. Neurobiol. 1997,14: 67-116.
[14] Oliveira EF, Mazzer N, Barbieri CH, et al. Correlation between functional index and morphometry to evaluate recovery of the rat sciatic nerve following crush injury: experimental study. J Reconstr Microsurg. 2001,17: 69-75.
[15]Raso VV, Barbieri CH, Mazzer N, et al. Can therapeutic ultrasound influence the regeneration of peripheral nerves? J. Neurosci. Methods. 2005,142: 185-192.
[16] Mazzer PY, Barbieri CH, Mazzer N, et al. Morphologic and morphometric evaluation of experimental acute crush injuries of the sciatic nerve of rats. J. Neurosci. Methods. 2008, 173: 249-258.
[17] Ide C. Peripheral nerve regeneration, Neurosci. Res. 1996,25: 101-121.
[18] Stoll G, Muller HW. Nerve injury, axonal degeneration and neural regeneration: basic insights. Brain Pathol. 1999, 9: 313-325.
[19] Committee of National Pharmacopoeia, Pharmacopoeia of the People's Republic of China, Chemical Industry Press, Beijing (2005) 49.
[20] Sakakima H, Yoshida Y, Morimoto N. The effect of denervation and subsequent reinnervation on the morphology of rat soleus muscels. J. Phys. Ther. Sci. 2002, 14: 21-26.
[21] Batt J, Bain J, Goncalves J. Differential gene expression profiling of short and long term denervated muscle. FASEB J. 2006, 20:115-117.
[22] Eisenberg HA, Hood DA. Blood flow, mitochondria, and performance in skeletal muscle after denervation and reinnervation, J. Appl. Physiol. 1994, 76: 859-866.
[23] White KK, Vaughan DW. Age effects on cytochrome oxidase activities during denervation and recovery of three muscle fiber types. Anat. Rec. 1991,230: 460-467.
1. Fry EJ, Ho C, David S. A role for Nogo receptor in macrophage clearance from injured peripheral nerve. Neuron. 2007;53(5):649-662.
2. Hirata K, Kawabuchi M. Myelin phagocytosis by macrophages and nonmacrophages during Wallerian degeneration. Microsc Res Tech. 2002 6;57(6):541-547.
3. Pu LL, Syed SA, Reid M, et al. Effects of nerve growth factor on nerve regeneration through a vein graft across a gap. Plast Reconstr Surg. 1999;104(5):1379-1385.
4. Reynolds ML, Woolf CJ. Reciprocal Schwann cell-axon interactions. Curr Opin Neurobiol. 1993;3(5):683-693.
5. Berthold CH, Nilsson RI. De- and remyelination in spinal roots during normal perinatal development in the cat: a brief summary of structural observations and a conceptual hypothesis. J Anat. 2002;200(4):391-403.
6. Son YJ, Thompson WJ. Schwann cell processes guide regeneration of peripheral axons. Neuron. 1995;14(1):125-132.
7. Hall S. Axonal regeneration through acellular muscle grafts. J Anat. 1997; 190:57-71.
8. Murphy RA, Acheson A, Hodges R, et al. Immunological relationships of NGF, BDNF, and NT-3: recognition and functional inhibition by antibodies to NGF. J Neurosci. 1993;13(7):2853-2862.
9. Terenghi G, Calder JS, Birch R, et al. A morphological study of Schwann cells and axonal regeneration in chronically transected human peripheral nerves. Journal of Hand Surgery. 1998;23(5):583-587.
10. Terris DJ, Fee WE Jr. Current issues in nerve repair. Arch Otolaryngol Head Neck Surg. 1993; 119(7):725-731.
11. Brushart TM. Motor axons preferentially reinnervate motor pathways. J Neurosci. 1993;13(6):2730-2738.
12. Skaper SD, Moore SE, Walsh FS. Cell signalling cascades regulating neuronal growth-promoting and inhibitory cues. Prog Neurobiol. 2001;65(6):593-608.
13. Edelman GM, Jones FS. Gene regulation of cell adhesion: a key step in neural morphogenesis. Brain Res Brain Res Rev. 1998;26(2-3):337-352.
14. Saad B, Constam DB, Ortmann R, et al. Astrocyte-derived TGF-beta 2 and NGF differentially regulate neural recognition molecule expression by cultured astrocytes. J Cell Biol. 1991 ;115(2):473-484.
15. Gu X, Thomas PK, King RH. Chemotropism in nerve regeneration studied in tissue culture. J Anat. 1995;186:153-163.
16. Madison RD, Robinson GA, Chadaram SR. The specificity of motor neurone regeneration (preferential reinnervation). Acta Physiol (Oxf). 2007; 189(2):201-206.
17. Madison RD, Archibald SJ, Brushart TM. Reinnervation accuracy of the rat femoral nerve by motor and sensory neurons. J Neurosci. 1996; 16(18):5698—5703.
18. Terzis JK, Smith KL. Repair and grafting of the peripheral nerve. In General Principles of Plastic Surgery (ed.McCarthy JG).1990: 630-697.
19. Hirata K, Kawabuchi M. Myelin phagocytosis by macrophages and nonmacrophages during Wallerian degeneration. Microsc Res Tech. 2002, 57: 541-547.
20. Chen ZL, Yu WM, Strickland S. Peripheral regeneration. Ann Rev Neurosci. 2007, 30: 209-233.
21. Scherer SS, Salzer JL. Axon-Schwann cell interactions during peripheral nerve degenerationand regeneraion. Oxford University Press, Oxford, 2001,299-330.
22. Hopkins SJ, Rothwell NJ. Cytokines and the nervous system. I: Expression and recognition. Trends Neurosci. 1995;18(2):83-88.
23. Kurihara H, Shinohara H, Yoshino H, et al. Neurotrophins in cultured cells from periodontal tissues. J Periodontol. 2003;74(1):76-84.
24. Davies AM. The neurotrophic hypothesis: where does it stand? Philos Trans R Soc Lond B Biol Sci. 1996;351(1338):389-394.
25. Rossi J, Airaksinen MS. GDNF family signalling in exocrine tissues: distinct roles for GDNF and neurturin in parasympathetic neuron development. Adv Exp Med Biol. 2002;506(Pt A):19-26.
26. Anand P, Terenghi G, Warner G, et al. The role of endogenous nerve growth factor in human diabetic neuropathy. Nat Med. 1996;2(6):703-707.
27. Hiltunen JO, Laurikainen A, Klinge E, et al.Neurotrophin-3 is a target-derived neurotrophic factor for penile erection-inducing neurons. Neuroscience. 2005;133(1):51-58.
28. Berkemeier LR, Winslow JW, Kaplan DR, et al. Neurotrophin-5: a novel neurotrophic factor that activates trk and trkB. Neuron. 1991 ;7(5):857—866.
29. Hallbook F, Ibanez CF, Persson H. Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary. Neuron. 1991;6(5):845-858.
30. Rodriguez-Tebar A, Dechant G, Gotz R, et al. Binding of neurotrophin-3 to its neuronal receptors and interactions with nerve growth factor and brain-derived neurotrophic factor. EMBO J. 1992; 11(3):917-922.
31. Chao MV, Hempstead BL. p75 and Trk: a two-receptor system. Trends Neurosci. 1995;18(7):321-326.
32. Gargano N, Levi A, Alema S. Modulation of nerve growth factor internalization by direct interaction between p75 and TrkA receptors. J Neurosci Res. 1997;50(1):1-12.
33. Anneren C, Lindholm CK, Kriz V, et al.The FRK/RAK-SHB signaling cascade: a versatile signal-transduction pathway that regulates cell survival, differentiation and proliferation.Curr Mol Med. 2003;3(4):313-324.
34. Klein R, Lamballe F, Bryant S, et al. The trkB tyrosine protein kinase is a receptor for neurotrophin-4. Neuron. 1992;8(5):947-956.
35. Davies AM, Minichiello L, Klein R. Developmental changes in NT3 signalling via TrkA and TrkB in embryonic neurons. EMBO J. 1995;14(18):4482-4489.
36. Ryden M, Ibanez CF. Binding of neurotrophin-3 to p75LNGFR, TrkA, and TrkB mediated by a single functional epitope distinct from that recognized by trkC. J Biol Chem. 1996;271(10):5623-5627.
37. Wright DE, Snider WD. Neurotrophin receptor mRNA expression defines distinct populations of neurons in rat dorsal root ganglia. J Comp Neurol. 1995;351(3):329-338.
38. Bennett DL, Dmietrieva N, Priestley JV, et al. TrkA, CGRP and IB4 expression in retrogradely labelled cutaneous and visceral primary sensory neurones in the rat. Neurosci Lett. 1996;206(1):33-36.
39. Davis-Lopez de Carrizosa MA, Morado-Diaz CJ, Tena JJ, et al. Complementary actions of BDNF and neurotrophin-3 on the firing patterns and synaptic composition of motoneurons. J Neurosci. 2009;29(2):575-587
40. Yoshizaki K, Yamamoto S, Yamada A, et al.Neurotrophic factor neurotrophin-4 regulates ameloblastin expression via full-length TrkB.J Biol Chem. 2008;283(6):3385-91.
41. Griesbeck O, Parsadanian AS, Sendtner M, et al. Expression of neurotrophins in skeletal muscle: quantitative comparison and significance for motoneuron survival and maintenance of function. J Neurosci Res. 1995;42(1):21-33.
42. Wood TK, McDermott KW, Sullivan AM. Differential effects of growth/differentiation factor 5 and glial cell line-derived neurotrophic factor on dopaminergic neurons and astroglia in cultures of embryonic rat midbrain. J Neurosci Res. 2005;80(6):759-766.
43. Baloh RH, Tansey MG, Golden JP, et al. TrnR2, a novel receptor that mediates neurturin and GDNF signaling through Ret. Neuron. 1997;18(5):793-802.
44. Bennett DL, Michael GJ, Ramachandran N, et al. A distinct subgroup of small DRG cells express GDNF receptor components and GDNF is protective for these neurons after nerve injury. J Neurosci. 1998;18(8):3059-3072.
45. Matheson CR, Wang J, Collins FD, et al. Long-term survival effects of GDNF on neonatal rat facial motoneurons after axotomy. Neuroreport. 1997;8(7): 1739—1742.
46. Park K, Luo JM, Hisheh S, et al.Cellular mechanisms associated with spontaneous and ciliary neurotrophic factor-cAMP-induced survival and axonal regeneration of adult retinal ganglion cells.J Neurosci. 2004;24(48):10806-10815.
47. Richardson PM. Ciliary neurotrophic factor: a review. Pharmacol Ther. 1994;63(2): 187-198.
48. Rende M, Muir D, Ruoslahti E, et al. Immunolocalization of ciliary neuronotrophic factor in adult rat sciatic nerve. Glia. 1992;5(1):25-32.
49. Helgren ME, Squinto SP, Davis HL, et al. Trophic effect of ciliary neurotrophic factor on denervated skeletal muscle. Cell. 1994;76(3):493-504.
50. Macosko JC, Newbern JM, Rockford J, et al.Fewer active motors per vesicle may explain slowed vesicle transport in chick motoneurons after three days in vitro.Brain Res. 2008;1211:6-12.
51. Adler R. Ciliary neurotrophic factor as an injury factor. Curr Opin Neurobiol. 1993;3(5):785-789.
52. Yamamori T, Fukada K, Aebersold R, et al. The cholinergic neuronal differentiation factor from heart cells is identical to leukemia inhibitory factor. Science. 1989;246(4936):1412-1416.
53. Thompson SW, Vernallis AB, Heath JK, et al. Leukaemia inhibitory factor is retrogradely transported by a distinct population of adult rat sensory neurons: co-localization with trkA and other neurochemical markers. Eur J Neurosci. 1997;9(6):1244-1251.
54. Michael GJ, Averill S, Nitkunan A, et al. Nerve growth factor treatment increases brain-derived neurotrophic factor selectively in TrkA-expressing dorsal root ganglion cells and in their central terminations within the spinal cord. J Neurosci. 1997; 17(21):8476-8490.
55. Carraway KL, 3rd, Burden SJ. Neuregulins and their receptors. Curr Opin Neurobiol. 1995;5(5):606-612.
56. Chen MS, Bermingham-McDonogh O, Danehy FT, et al. Expression of multiple neuregulin transcripts in postnatal rat brains. J Comp Neurol. 1994;349(3):389-400.
57. Dong Z, Brennan A, Liu N, et al. Neu differentiation factor is a neuron-glia signal and regulates survival, proliferation, and maturation of rat Schwann cell precursors. Neuron. 1995;15(3):585-596.
58. Trachtenberg JT, Thompson WJ. Schwann cell apoptosis at developing neuromuscular junctions is regulated by glial growth factor. Nature. 1996;379(6561):174—177.
59. Castro C, Kuffler DP. Membrane-bound CSPG mediates growth cone outgrowth and substrate specificity by Schwann cell contact with the DRG neuron cell body and not via growth cone contact.Exp Neurol. 2006;200(1):19-25.
60. Oakley RA, Garner AS, Large TH, et al. Muscle sensory neurons require neurotrophin-3 from peripheral tissues during the period of normal cell death. Development. 1995;121(5):1341-1350.
61. Rush RA, Chie E, Liu D, et al. Neurotrophic factors are required by mature sympathetic neurons for survival, transmission and connectivity. Clin Exp Pharmacol Physiol. 1997;24(8):549-555.
62. Molliver DC, Wright DE, Leitner ML, et al. IB4-binding DRG neurons switch from NGF to GDNF dependence in early postnatal life. Neuron. 1997;19(4):849-861.
63. Jivan S, Novikova LN, Wiberg M, et al. The effects of delayed nerve repair on neuronal survival and axonal regeneration after seventh cervical spinal nerve axotomy in adult rats. Exp Brain Res. 2006;170(2):245-254.
64. Groves MJ, Christopherson T, Giometto B, et al. Axotomy-induced apoptosis in adult rat primary sensory neurons. J Neurocytol. 1997;26(9):615-624.
65. Krekoski CA, Parhad IM, Clark AW. Attenuation and recovery of nerve growth factor receptor mRNA in dorsal root ganglion neurons following axotomy. J Neurosci Res. 1996, 43(1): 1-11.
66. Verge VM, Gratto KA, Karchewski LA, et al. Neurotrophins and nerve injury in the adult. Philos Trans R Soc Lond B Biol Sci. 1996;351(1338):423-430.
67. Munson JB, Shelton DL, McMahon SB. Adult mammalian sensory and motor neurons: roles of endogenous neurotrophins and rescue by exogenous neurotrophins after axotomy. J Neurosci. 1997;17(1):470-476.
68. Anand P, Terenghi G, Birch R, et al. Endogenous NGF and CNTF levels in human peripheral nerve injury. Neuroreport. 1997;8(8):1935-1938.
69. Robertson MD, Toews AD, Bouldin TW, et al. NGFR-mRNA expression in sciatic nerve: a sensitive indicator of early stages of axonopathy. Brain Res Mol Brain Res. 1995;28(2):231-238.
70. Anton ES, Weskamp G, Reichardt LF, et al. Nerve growth factor and its low-affinity receptor promote Schwann cell migration. Proc Natl Acad Sci U S A. 1994;91(7):2795-2799.
71. Thippeswamy T, Howard MR, Cosgrave AS, et al.Nitric oxide-NGF mediated PPTA/SP, ADNP, and VIP expression in the peripheral nervous system.J Mol Neurosci. 2007;33(3):268-277.
72. Shadiack AM, Sun Y, Zigmond RE. Nerve growth factor antiserum induces axotomy-like changes in neuropeptide expression in intact sympathetic and sensory neurons. J Neurosci. 2001;21(2):363-371.
73. Zhang X, Ji RR, Nilsson S, et al. Neuropeptide Y and galanin binding sites in rat and monkey lumbar dorsal root ganglia and spinal cord and effect of peripheral axotomy. Eur J Neurosci. 1995;7(3):367-380.
74. Wakisaka S, Takikita S, Youn SH, et al. Partial coexistence of neuropeptide Y and calbindin D28k in the trigeminal ganglion following peripheral axotomy of the inferior alveolar nerve in the rat. Brain Res. 1996;707(2):228-234.
75. Mulderry PK. Neuropeptide expression by newborn and adult rat sensory neurons in culture: effects of nerve growth factor and other neurotrophic factors. Neuroscience. 1994;59(3):673-688.
76. Kerekes N, Landry M, Rydh-Rinder M, et al. The effect of NGF, BDNF and bFGF on expression of galanin in cultured rat dorsal root ganglia. Brain Res. 1997;754(1-2):131-141.
77. Bucelli RC, Gonsiorek EA, Kim WY, et al.Statins decrease expression of the proinflammatory neuropeptides calcitonin gene-related peptide and substance P in sensory neurons. J Pharmacol Exp Ther. 2008;324(3): 1172-1180.
78. Ohara S, Tantuwaya V, DiStefano PS, et al. Exogenous NT-3 mitigates the transganglionic neuropeptide Y response to sciatic nerve injury. Brain Res. 1995;699(1):143-148.
79. Thompsons WN,Priestley JV,Southalla. gp130 cytokines, leukaemia inhibitory factor and interleukin-6 induce neuropeptide expression in intact adult rat sensory neurons in vivo:time-course, specificity and comparison with sciatic nerve axotomy. Neuroscience.1998;84:1247-1255.
80. Cho HJ, Kim SY, Park MJ, et al. Expression of mRNA for brain-derived neurotrophic factor in the dorsal root ganglion following peripheral inflammation. Brain Res. 1997;749(2):358-362.
81. Zhou XF, Li WP, Zhou FH, et al. Differential effects of endogenous brain-derived neurotrophic factor on the survival of axotomized sensory neurons in dorsal root ganglia: a possible role for the p75 neurotrophin receptor. Neuroscience. 2005;132(3):591-603.
82. Kashiba H, Ueda Y, Ueyama T, et al. Relationship between BDNF- and trk-expressing neurones in rat dorsal root ganglion: an analysis by in situ hybridization. Neuroreport. 1997;8(5):1229-1234.
83. Skoff AM, Adler JE. Nerve growth factor regulates substance P in adult sensory neurons through both TrkA and p75 receptors.Exp Neurol. 2006;197(2):430-436.
84. Zhou XF, Rush RA. Endogenous brain-derived neurotrophic factor is anterogradely transported in primary sensory neurons. Neuroscience. 1996;74(4):945—953.
85. James R, Tonra JR, Curts R, et al. Axotomy upregulates the anterograde transport and expression of brain derived neurotrophic factor in sensory neurons. Journal of Neuroscience.1998;18:4371-4383.
86. Carroll SL, Miller ML, Frohnert PW, et al. Expression of neuregulins and their putative receptors, ErbB2 and ErbB3, is induced during Wallerian degeneration. J Neurosci. 1997;17(5):1642-1659.
87. Kuo LT, Groves MJ, Scaravilli F, et al. Neurotrophin-3 administration alters neurotrophin, neurotrophin receptor and nestin mRNA expression in rat dorsal root ganglia following axotomy .Neuroscience. 2007;147(2):491-507.
88. Rende M, Provenzano C, Tonali P. Modulation of low-affinity nerve growth factor receptor in injured, adult rat spinal cord motoneurons. J Comp Neurol. 1993 ;338(4):560-574.
89. Rende M, Provenzano C, Stipa G, et al. Effects of sciatic nerve grafts on choline acetyltransferase and p75 expression in transected adult hypoglossal motoneurons. Neuroscience. 1997;81(2):517-525.
90. Yan Q, Elliott J, Snider WD. Brain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death. Nature. 1992;360(6406):753-755.
91. Novikova L, Novikov L, Kellerth JO. Effects of neurotransplants and BDNF on the survival and regeneration of injured adult spinal motoneurons. Eur J Neurosci. 1997;9(12):2774-2777.
92. Kishino A, Ishige Y, Tatsuno T, et al.BDNF prevents and reverses adult rat motor neuron degeneration and induces axonal outgrowth. Exp Neurol. 1997;144(2):273-286.
93. Kasahara K, Nakagawa T, Kubota T. Neuronal loss and expression of neurotrophic factors in a model of rat chronic compressive spinal cord injury. Spine. 2006;31(18):2059-2066.
94. Sendtner M, Gotz R, Holtmann B, et al. Endogenous ciliary neurotrophic factor is a lesion factor for axotomized motoneurons in adult mice. J Neurosci. 1997;17(18):6999-7006.
95. Hiruma S, Shimizu T, Huruta T, et al. Ciliary neurotrophic factor immunoreactivity in rat intramuscular nerve during reinnervation through a silicone tube after severing of the rat sciatic nerve. Exp Mol Pathol. 1997;64(1):23-30.
96. Newman JP, Verity AN, Hawatmeh S, et al. Ciliary neurotrophic factors enhances peripheral nerve regeneration. Arch Otolaryngol Head Neck Surg. 1996;122(4):399-403.
97. Zhang J, Lineaweaver WC, Oswald T, et al. Ciliary neurotrophic factor for acceleration of peripheral nerve regeneration: an experimental study. J Reconstr Microsurg. 2004;20(4):323-327.
98. Curtis R, Scherer SS, Somogyi R, et al. Retrograde axonal transport of LIF is increased by peripheral nerve injury: correlation with increased LIF expression in distal nerve. Neuron. 1994; 12(1):191—204.
99. Matsuoka I, Nakane A, Kurihara K. Induction of LIF-mRNA by TGF-beta 1 in Schwann cells. Brain Res. 1997;776(1-2):170-180.
100.Tham S, Dowsing B, Finkelstein D, et al. Leukemia inhibitory factor enhances the regeneration of transected rat sciatic nerve and the function of reinnervated muscle. J Neurosci Res. 1997;47(2):208-215.
101.White JD, Davies M, Grounds MD. Leukaemia inhibitory factor increases myoblast replication and survival and affects extracellular matrix production: combined in vivo and in vitro studies in post-natal skeletal muscle. Cell Tissue Res. 2001;306(1):129-141.
102.Tessarollo L, Vogel KS, Palko ME, et al. Targeted mutation in the neurotrophin-3 gene results in loss of muscle sensory neurons. Proc Natl Acad Sci U S A. 1994;91(25):11844-11848.
103.Oakley RA, Lefcort FB, Clary DO, et al. Neurotrophin-3 promotes the differentiation of muscle spindle afferents in the absence of peripheral targets. J Neurosci. 1997;17(11):4262-4274.
104.Chen J, Qi JG, Zhang W, et al.Electro-acupuncture induced NGF, BDNF and NT-3 expression in spared L6 dorsal root ganglion in cats subjected to removal of adjacent ganglia.Neurosci Res. 2007;59(4):399-405.
105.Sterne GD, Coulton GR, Brown RA, et al. Neurotrophin-3-enhanced nerve regeneration selectively improves recovery of muscle fibers expressing myosin heavy chains 2b. J Cell Biol. 1997;139(3):709-715.
106.Chan JR, Cosgaya JM, Wu YJ, et al. Neurotrophins are key mediators of the myelination program in the peripheral nervous system. Proc Natl Acad Sci USA. 2001, 98: 14661-14668.
107.Yan Q, Matheson C, Lopez OT. In vivo neurotrophic effects of GDNF on neonatal and adult facial motor neurons. Nature. 1995;373(6512):341-344.
108.Nguyen QT, Parsadanian AS, Snider WD, et al. Hyperinnervation of neuromuscular junctions caused by GDNF overexpression in muscle. Science. 1998;279(5357): 1725-1729.
109.Hoke A, Gordon T, Zochodne DW, et al. A decline in glial cell-line-derived neurotrophic factor expression is associated with impaired regeneration after long-term Schwann cell denervation. Exp Neurol. 2002;173(1):77-85.
110.Naveilhan P, ElShamy WM, Ernfors P. Differential regulation of mRNAs for GDNF and its receptors Ret and GDNFR alpha after sciatic nerve lesion in the mouse. Eur J Neurosci. 1997;9(7): 1450-1460.
111.Mendell LM. Neurotrophins and sensory neurons: role in development, maintenance and injury. A thematic summary. Philos Trans R Soc Lond B Biol Sci. 1996;351(1338):463-467.
112.Whitworth IH, Brown RA, Dore CJ, et al. Nerve growth factor enhances nerve regeneration through fibronectin grafts. J Hand Surg [Br]. 1996;21(4):514-522.
113. Jivan S, Novikova LN, Wiberg M, et al.The effects of delayed nerve repair on neuronal survival and axonal regeneration after seventh cervical spinal nerve axotomy in adult rats. Exp Brain Res. 2006 ;170(2):245-254.
114.Gold BG. Axonal regeneration of sensory nerves is delayed by continuous intrathecal infusion of nerve growth factor. Neuroscience. 1997;76(4):1153-1158.
115.Zhu QT, Zhu JK, Chen GY. Location of collateral sprouting of donor nerve following end-to-side neurorrhaphy.Muscle Nerve. 2008;38(5): 1506-1509.
116.Sterne GD, Brown RA, Green CJ, et al. Neurotrophin-3 delivered locally via fibronectin mats enhances peripheral nerve regeneration. Eur J Neurosci. 1997;9(7):1388-1396.
117.Munson JB, McMahon SB. Effects of GDNF on axotomized sensory and motor neurons in adult rats. Eur J Neurosci. 1997;9(6):1126-1129.
118.Helgren ME, Cliffer KD, Torrento K, et al. Neurotrophin-3 administration attenuates deficits of pyridoxine-induced large-fiber sensory neuropathy. J Neurosci. 1997; 17(1): 372-382.
119.Lewin SL, Utley DS, Cheng ET, et al. Simultaneous treatment with BDNF and CNTF after peripheral nerve transection and repair enhances rate of functional recovery compared with BDNF treatment alone. Laryngoscope. 1997;107(7):992-999.
120.Papakostas I, Mourouzis I, Mourouzis K, et al. Functional effects of local thyroid hormone administration after sciatic nerve injury in rats.Microsurgery. 2009;29(1):35-41.
121.Subang MC, Bisby MA, Richardson PM. Delay of CNTF decrease following peripheral nerve injury in C57BL/WW mice. J Neurosci Res. 1997;49(5):563-568.
122.You S, Petrov T, Chung PH, et al. The expression of the low affinity nerve growth factor receptor in long-term denervated Schwann cells. Glia. 1997;20(2):87-100.
123.McAllister AK, Katz LC, Lo DC. Opposing roles for endogenous BDNF and NT-3 in regulating cortical dendritic growth. Neuron. 1997;18(5):767-778.
124.Roehm PC, Hansen MR. Strategies to preserve or regenerate spiral ganglion neurons. Curr Opin Otolaryngol Head Neck Surg. 2005;13(5):294-300.
125.Arce V, Pollock RA, Philippe JM, et al. Synergistic effects of schwann- and muscle-derived factors on motoneuron survival involve GDNF and cardiotrophin-1 (CT-1). J Neurosci. 1998;18(4):1440-1448.
126.Lindsay RM. Therapeutic potential of the neurotrophins and neurotrophin-CNTF combinations in peripheral neuropathies and motor neuron diseases. Ciba Found Symp. 1996;196:39-53.
127.Hoffer B, Olson L. Treatment strategies for neurodegenerative diseases based on trophic factors and cell transplantation techniques. J Neural Transm Suppl. 1997;49:l-10.
128.Strand AD, Baquet ZC, Aragaki AK, et al.Expression profiling of Huntington's disease models suggests that brain-derived neurotrophic factor depletion plays a major role in striatal degeneration.J Neurosci. 2007;27(43):11758-11768.