Traumatic brain injury(TBI)is the main cause of disability,mental health disorder,and even death,with its incidence and social costs rising steadily.Although different treatment strategies have been developed and test...Traumatic brain injury(TBI)is the main cause of disability,mental health disorder,and even death,with its incidence and social costs rising steadily.Although different treatment strategies have been developed and tested to mitigate neurological decline,a definitive cure for these conditions remains elusive.Studies have revealed that vari-ous neurotrophins represented by the brain-derived neurotrophic factor are the key regulators of neuroinflammation,apoptosis,blood-brain barrier permeability,neurite regeneration,and memory function.These factors are instrumental in alleviating neu-roinflammation and promoting neuroregeneration.In addition,neural stem cells(NSC)contribute to nerve repair through inherent neuroprotective and immunomodulatory properties,the release of neurotrophins,the activation of endogenous NSCs,and in-tercellular signaling.Notably,innovative research proposals are emerging to combine BDNF and NSCs,enabling them to synergistically complement and promote each other in facilitating injury repair and improving neuron differentiation after TBI.In this review,we summarize the mechanism of neurotrophins in promoting neurogen-esis and restoring neural function after TBI,comprehensively explore the potential therapeutic effects of various neurotrophins in basic research on TBI,and investigate their interaction with NSCs.This endeavor aims to provide a valuable insight into the clinical treatment and transformation of neurotrophins in TBI,thereby promoting the progress of TBI therapeutics.展开更多
Objective Cloning and sequencing of the human neurotrophin 4 gene.Methods With the chromosomal DNA of human blood lymphocytes as template,hNT 4 coding genes were amplified by polymerase chain reaction and recombinated...Objective Cloning and sequencing of the human neurotrophin 4 gene.Methods With the chromosomal DNA of human blood lymphocytes as template,hNT 4 coding genes were amplified by polymerase chain reaction and recombinated into phage vector pGEM T Easy,which were sequenced by using Sanger’s single stranded DNA terminal termination method.Results The sequence of the cloned gene is completely the same as that reported in the literature.Conclusion This study successfully cloning and sequenced the gene of mhNT 4,and it would be convenient for us to study the expression of mhNT 4 in eukaryote,and to continue the research on the gene therapy of Alzheimer’s disease intensively.This study indicate that the hNT 4 is conservative in different races and individuals.展开更多
Brain-derived neurotrophic factor(BDNF),a critical neurotrophin,regulates many neuronal aspects including cell differentiation,cell survival,neurotransmission,and synaptic plasticity in the central nervous system(CNS)...Brain-derived neurotrophic factor(BDNF),a critical neurotrophin,regulates many neuronal aspects including cell differentiation,cell survival,neurotransmission,and synaptic plasticity in the central nervous system(CNS) .Though BDNF has two types of receptors,high affinity tropomyosin-related kinase(Trk) B and low affinity p75 receptors,BDNF positively exerts its biological effects on neurons via activation of TrkB and of resultant intracellular signaling cascades including mitogenactivated protein kinase/extracellular signal-regulated protein kinase,phospholipase Cγ,and phosphoinositide 3-kinase pathways.Notably,it is possible that alteration in the expression and/or function of BDNF in the CNS is involved in the pathophysiology of various brain diseases such as stroke,Parkinson's disease,Alzheimer's disease,and mental disorders.On the other hand,glucocorticoids,stress-induced steroid hormones,also putatively contribute to the pathophysiology of depression.Interestingly,in addition to the reduction in BDNF levels due to increased glucocorticoid exposure,current reports demonstrate possible interactions between glucocorticoids and BDNF-mediated neuronal functions. Other steroid hormones,such as estrogen,are involved in not only sexual differentiation in the brain,but also numerous neuronal events including cell survival and synaptic plasticity.Furthermore,it is well known that estrogen plays a role in the pathophysiology of Parkinson's disease,Alzheimer's disease,and mental illness,while serving to regulate BDNF expression and/or function.Here,we present a broad overview of the current knowledge concerning the association between BDNF expression/function and steroid hormones(glucocorticoids and estrogen).展开更多
The many important benefits of physical exercise also encompass maintenance or improvement of cognitive functions. Among the variousmechanisms underlying the association between physical exercise and brain health, rec...The many important benefits of physical exercise also encompass maintenance or improvement of cognitive functions. Among the variousmechanisms underlying the association between physical exercise and brain health, recent evidence attests that neurotrophin receptor signalingmay have an important role, because the activation of this pathway leads to growth and differentiation of new neurons and synapses, supportsaxonal and dendritic growth, fosters synaptic plasticity, and preserves survival of existing neurons. In this review of published evidence, we highlightthat a positive relationship exists between physical exercise and circulating brain-derived neurotrophic factor levels and that the postexercisevariation of this molecule is associated with improvement of neurocognitive functioning. Less clear evidence has instead been published forother neurotrophins, such as nerve growth factor, neurotrophin-3, and neurotrophin-4. Overall, promotion of adequate volumes and intensities ofphysical exercise (i.e., approximately 3 months of moderate-intensity aerobic exercise, with 2—3 sessions/week lasting not less than 30 min)may hence be regarded as an inexpensive and safe strategy for boosting brain-derived neurotrophic factor release, thus preserving or restoringcognitive functions.展开更多
The role of neurotrophins in neuronal plasticity has recently become a strong focus in neuroregeneration research field to elucidate the biological mechanisms by which these molecules modulate synapses,modify the resp...The role of neurotrophins in neuronal plasticity has recently become a strong focus in neuroregeneration research field to elucidate the biological mechanisms by which these molecules modulate synapses,modify the response to injury,and alter the adaptation response.Intriguingly,the prior studies highlight the role of p75 neurotrophin receptor(p75^(NTR))in various injuries and diseases such as central nervous system injuries,Alzheimer's disease and amyotrophic lateral sclerosis.More comprehensive elucidation of the mechanisms,and therapies targeting these molecular signaling networks may allow for neuronal tissue regeneration following an injury.Due to a diverse role of the p75^(NTR)in biology,the body of evidence comprising its biological role is diffusely spread out over numerous fields.This review condenses the main evidence of p75^(NTR)for clinical applications and presents new findings from published literature how data mining approach combined with bioinformatic analyses can be utilized to gain new hypotheses in a molecular and network level.展开更多
Neurotrophins (NTs) are implicated in the maintenance and survival of the peripheral and central nervous systems and mediate several forms of synaptic plasticity. Members of the family include nerve growth factor (NGF...Neurotrophins (NTs) are implicated in the maintenance and survival of the peripheral and central nervous systems and mediate several forms of synaptic plasticity. Members of the family include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NT3, and NT4. NTs were first identified as survival factors for developing neurons, but are pleiotropic molecules that can exert a variety of functions, including the regulation of neuronal differentiation, axonal and dendritic growth, and synaptic plasticity (Bothwell, 2014). NTs interact with two distinct types of receptors: the common p75 neurotrophin receptor, which belongs to the tumor necrosis factor receptor superfamily of death receptors and the Trk receptor tyrosine kinase family.展开更多
This manuscript reviews the function and fundamental characteristics of the neurotrophins and their receptors to introduce the reader to the differential effects exhibited by the neurotrophins;brain-derived neurotroph...This manuscript reviews the function and fundamental characteristics of the neurotrophins and their receptors to introduce the reader to the differential effects exhibited by the neurotrophins;brain-derived neurotrophic factor and neurotrophin 4/5 when acted together after sequential presentation.The neurotrophin 4/5 exhibits an inhibitory action on the modulatory effect of brain-derived neurotrophic factor in corticostriatal synapses when they are administered sequentially(brain-derived neurotrophic factor to neurotrophin 4/5).This inhibitory effect has not been previously documented and is relevant for these neurotrophins as both of them stimulate the TrkB receptor.The additive effect of these neurotrophins is also discussed and occurs when neurotrophin 4/5 exposure is followed by brain-derived neurotrophic factor in a mouse model of striatal degeneration.Occlusive and additive effects of both neurotrophins are accompanied by changes in the expression of the TrkB receptor isoforms,specifically TrkB-T1 and TrkB-FL,as well as differences in phosphorylation levels of the TrkB receptor.The results of the experiments described raise several questions to inquire about the role that TrkB-T1 receptor plays in striatal physiology,as well as the functional relevance of the interaction of brain-derived neurotrophic factor and neurotrophin 4/5 in the brain and more specifically at the striatal circuits in normal as well as pathological conditions.展开更多
Neurotrophic factors are able to promote neuronalsurvival and prevent neuronal death induced by variousinjuries and have potential uses in the treatment ofneuronal degenerative diseases and neuropathy. Due tothe exist...Neurotrophic factors are able to promote neuronalsurvival and prevent neuronal death induced by variousinjuries and have potential uses in the treatment ofneuronal degenerative diseases and neuropathy. Due tothe existence of brain blood barrier, neurotrophic factorscan not be ased in CNS diseases directly. Gene therapy isa good candidate to overcome this problem.展开更多
BACKGROUND:Nogo-neutralizing antibody IN-1 accelerates axon growth and enhances recovery of spinal cord function by inhibiting growth inhibitory factors. Neurotrophin-3 (NT-3)contributes to regeneration of nerve fiber...BACKGROUND:Nogo-neutralizing antibody IN-1 accelerates axon growth and enhances recovery of spinal cord function by inhibiting growth inhibitory factors. Neurotrophin-3 (NT-3)contributes to regeneration of nerve fibers in the spinal cord and motor function recovery. The combination of Nogo-neutralizing antibody IN-1 and NT-3 is hypothesized to produce better outcomes and facilitate axonal regeneration by affecting c-Fos and c-Jun protein expression. OBJECTIVE:To investigate the combined effects of Nogo-neutralizing antibody IN-1 and NT-3 on c-Fos and c-Jun protein levels in the injured spinal cord. DESIGN,TIME AND SETTING:A randomized,controlled study was performed at the Laboratory of Neuroanatomy,Xiangya Medical College,Central South University and the Central Laboratory of Third Xiangya Hospital of China from June 2005 to December 2007. MATERIALS:NT-3 (Peprotech,USA) and Nogo-neutralizing antibody IN-1 (Santa Cruz Biotechnology,USA) were used in this study. METHODS:Hemisectioned spinal cord injury models were established by cutting the posterior 2/3 of rat spinal cord,which is equivalent to the T8 level in the human spine. A total of 120 rats were equally and randomly assigned to three groups:model (0.2 μL saline),IN-1 (0.2 μL IN-1),and IN-1/NT-3 (0.2 μL IN-1 + 0.2 μL NT-3). The compounds were separately infused into transection sites on the side of head. MAIN OUTCOME MEASURES:Western blot analysis was employed to measure c-Fos and c-Jun protein expression in the injured spinal cord at 15,30 minutes,1,2,4,6,8,and 12 hours following surgery. RESULTS:Following spinal cord injury,c-Fos and c-Jun protein expression were increased and peaked at 4-6 hours. Following injection of IN-1 or the combination of IN-1 and NT-3,c-Fos protein expression was significantly reduced in the injured spinal cord (P < 0.05 or P < 0.01) (with the exception of the 15 minute time point). However,c-Jun protein expression was significantly increased (P < 0.05 or P < 0.01) (with the exception of the 15 and 30 minute time points). Combined application of IN-1 and NT-3 resulted in significantly altered protein expression compared to IN-1 alone. CONCLUSION:IN-1 increases c-Jun protein levels and protects the injured spinal cord by inhibiting c-Fos protein levels. Moreover,the effects of IN-1 combined with NT-3 are more significant than with IN-1 alone.展开更多
Bioactive proteins from SD rat limb buds were extracted and purified.Fractions of 22 ku, 34 ku and 95 ku were proved to have neurotrophic activity to neurons, and the combined activity of these three fractions was the...Bioactive proteins from SD rat limb buds were extracted and purified.Fractions of 22 ku, 34 ku and 95 ku were proved to have neurotrophic activity to neurons, and the combined activity of these three fractions was the highest. So they were combinedly added into the culture medium of sensor neurons in dorsal root ganglia and motor neurons of anterior spinal cord from 2-week-old embryonic rats, and PBS was added as control. Phase-contrast microscopic and electron microscopic observations, and true cholinesterase measurements were performed to evaluate the survival and changes in growth, function, and ultrastructure of these cultured neurons. In the experimental group, it was found that the AchE activity was higher (P【0.01), ultrastructural changes in mitochondria,Gorgi’s complex and other cell organs were milder than those in the control group. The results showed limb buds derived neurotrophins played an important role in maitaining the survival of the neurons and promoting the growth of axons. It was展开更多
Objective:To study the effect and mechanism of neurotrophin 3 (NT-3) on inhibiting dexamethasone (DEX)-induced mouse MC3T3-E1 osteoblast apoptosis.Methods:Mouse MC3T3-E1 osteoblasts were cultured and divided into grou...Objective:To study the effect and mechanism of neurotrophin 3 (NT-3) on inhibiting dexamethasone (DEX)-induced mouse MC3T3-E1 osteoblast apoptosis.Methods:Mouse MC3T3-E1 osteoblasts were cultured and divided into groups. Control group were treated with DMEM without drugs, DEX group were treated with DMEM containing 5μmol/L dexamethasone, and NT-3 group were treated with DMEM containing 5μmol/L dexamethasone and 100ng/mL NT-3. Apoptosis rate, proliferation viability, osteogenesis marker contents as well as apoptosis gene and PI3K/AKT/mTOR signaling pathway molecule expression were detected.Results: The apoptosis rate as well as bax and caspase-3 expression in the cells of DEX group was significantly higher than those of control group, whereas proliferation viability value, ALP, OCN and COL-I contents in the medium as well as bcl-2, p-PI3K, p-AKT and p-mTOR expression in the cells were significantly lower than those of control group (P<0.05);the apoptosis rate as well as bax and caspase-3 expression in the cells of NT-3 group was significantly lower than those of DEX group, whereas proliferation viability value, ALP, OCN and COL-I contents in the medium as well as bcl-2, p-PI3K, p-AKT and p-mTOR expression in the cells were significantly higher than those of DEX group (P<0.05).Conclusion:NT-3 has inhibiting effect on the dexamethasone-induced mouse MC3T3-E1 osteoblast apoptosis, and the possible mechanism of this effect is to activate the PI3K/AKT/mTOR signaling pathway.展开更多
Objective Neurotrophin 3(NTF3)is involved in numerous biological processes;however,its role in hepatocellular carcinoma(HCC)is not well studied.This study investigated NTF3 function in HCC progression and revealed its...Objective Neurotrophin 3(NTF3)is involved in numerous biological processes;however,its role in hepatocellular carcinoma(HCC)is not well studied.This study investigated NTF3 function in HCC progression and revealed its underlying molecular mechanisms.Methods The prognostic relevance of NTF3 was determined through a bioinformatical analysis of publicly available TCGA data.Immunohistochemistry of HCC biopsies was performed to explore the expression of NTF3.Cell growth and proliferation were analyzed using a Cell Counting Kit-8(CCK-8)assay.Cell invasion and migration were analyzed using Boyden Transwell and wound healing assays.Protein expression and mRNA levels were evaluated through immunoblotting and quantitative polymerase chain reaction(qPCR).Cell apoptosis was evaluated with flow cytometry.Results NTF3 expression was significantly lower in HCC tissues than in adjacent non-tumor tissues.Low NTF3 expression was significantly associated with decreased patient survival and specific clinicopathological features.NTF3 overexpression reduced the proliferation,migration,and invasion abilities of HCC cell lines.Conclusion Decreased expression of NTF3 is associated with poor prognosis in HCC patients,likely due to its action in promoting HCC cell proliferation,migration,and invasion.Our findings provide a novel understanding into the pathogenesis of HCC and the role of NTF3 in tumor progression,suggesting that targeting NTF3 has potential therapeutic and diagnostic value for HCC.展开更多
Objective:To investigate the correlation among the expression of neurotrophins (NTs) family and its receptors with cell proliferation and invasion in ovarian cancer.Methods:Ninety patients with ovarian cancer who unde...Objective:To investigate the correlation among the expression of neurotrophins (NTs) family and its receptors with cell proliferation and invasion in ovarian cancer.Methods:Ninety patients with ovarian cancer who underwent surgical treatment in Guangyuan First People's Hospital between December 2015 and October 2017 were selected as ovarian cancer group, and 67 patients with ovarian chocolate cyst were selected as benign lesion group. The differences in the expression of NTs family and its receptors, proliferation genes and invasion genes in lesions were compared between the two groups, and Pearson test was used to further evaluate the correlation among the expression of NTs family and its receptors with cancer cell malignancy in ovarian cancer tissue.Results:NT-3 mRNA expression in ovarian cancer group was lower than that in benign lesion group whereas NT-5, TrkA, TrkB and TrkC mRNA expression were higher than those in benign lesion group;proliferation genes FUNDC1, GRP78, PTTG and SMG-1 mRNA expression were higher than those in benign lesion group whereas shSASH1 and ESRP1 mRNA expression were lower than those in benign lesion group;invasion genes Clusterin, EFEMP1, Twist and IFITM1 mRNA expression were higher than those in benign lesion group whereas DUSP10 mRNA expression was lower than that in benign lesion group. Pearson test showed that the NT-5, TrkA, TrkB AND TrkC mRNA expression in ovarian cancer were directly correlated with cancer cell proliferation and invasion activity.Conclusion: The expression levels of NTs family and its receptors are abnormal in ovarian cancer and the specific expression levels are directly correlated with the proliferation and invasion activity of cancer cells.展开更多
<正>BACKGROUND:Many methods have been attempted to repair nerves following spinal cord injury, including peripheral nerve transplantation,Schwann cell transplantation,olfactory ensheathing cell transplantation,a...<正>BACKGROUND:Many methods have been attempted to repair nerves following spinal cord injury, including peripheral nerve transplantation,Schwann cell transplantation,olfactory ensheathing cell transplantation,and embryonic neural tissue transplantation.However,there is a need for improved outcomes. OBJECTIVE:To investigate the repair feasibility for rat spinal cord injury using human neural stem cells(hNSCs) genetically modified by lentivirus to express neurotrophin-3. DESIGN,TIME AND SETTING:In vitro cell biological experiment and in vivo randomized,controlled, genetic engineering experiment were performed at the Third Military Medical University of Chinese PLA and First People's Hospital of Yibin,China from March 2006 to December 2007. MATERIALS:A total of 64 adult,female,Wistar rats were used for the in vivo study.Of them,48 rats were used to establish models of spinal cord hemisection,and were subsequently equally and randomly assigned to model,genetically modified hNSC,and normal hNSC groups.The remaining 16 rats served as normal controls. METHODS:hNSCs were in vitro genetically modified by lentivirus to secrete both green fluorescence protein and neurotrophin-3.Neurotrophin-3 expression was measured by Western blot. Genetically modified hNSC or normal hNSC suspension(5×10~5) was injected into the rat spinal cord following T_(10) spinal cord hemisection.A total of 5μL Dulbecco's-modified Eagle's medium was infused into the rat spinal cord in the model group.Transgene expression and survival of transplanted hNSCs were determined by immunohistochemistry.Motor function was evaluated using the Basso,Beattie,and Bresnahan(BBB) scale. MAIN OUTCOME MEASURES:The following parameters were measured:expression of neurotrophin-3 produced by genetically modified hNSCs,transgene expression and survival of hNSCs in rats,motor function in rats. RESULTS:hNSCs were successfully genetically modified by lentivirus to stably express neurotrophin-3.The transplanted hNSCs primarily gathered at,or around,the injection site two weeks following transplantation,and gradually migrated towards the surrounding tissue. Transplanted hNSCs were observed 7.0-8.0 mm away from the injection site.In addition,hNSCs were observed 10 weeks after transplantation.At week 4,BBB locomotor scores were significantly greater in the genetically modified hNSC and normal hNSC groups,compared with the model group (P<0.05),and scores were significantly greater in the genetically modified hNSC group compared with the normal hNSC group(P<0.05). CONCLUSION:hNSCs were genetically modified with lentivirus to stably secrete neurotrophin-3. hNSCs improved motor function recovery in rats following spinal cord injury.展开更多
BACKGROUND: Recent studies have suggested that regeneration of the central nerve fiber following spinal cord injury occurs under specific conditions. OBJECTIVE: To study the effects of Nogo-neutralizing antibody (IN-1...BACKGROUND: Recent studies have suggested that regeneration of the central nerve fiber following spinal cord injury occurs under specific conditions. OBJECTIVE: To study the effects of Nogo-neutralizing antibody (IN-1), in combination with neurotrophin-3 (NT-3), on axonal regeneration and motor function following spinal cord injury in the rat. DESIGN, TIME AND SETTING: A randomized, controlled, animal study combining immunohistochemistry was performed at the Laboratory of Neuroanatomy of Xiangya Medical College, and Central Laboratory of Xiangya the Third Hospital, Central South University from January 2006 to December 2007. MATERIALS: Eighteen healthy, Sprague Dawley rats were randomly divided into three groups, with six rats per group: control, IN-1, and IN-1/NT-3. Hemisectioned spinal cord injury models were established by cutting the posterior 2/3 of spinal cord, which is equivalent to the T8 level. METHODS: A polyethylene tubing was inserted through into subarachnoid cavity, equivalent to the superior margin at the T8 level. Saline, IN-1, and IN-1/NT-3 were respectively injected into control, IN-1, and IN-1/NT-3 groups, three times/day for seven consecutive days. MAIN OUTCOME MEASURES: At 2 weeks post-surgery, biotin dextran amine (10%) was injected into the right sensorimotor cortex area. At day 28 post-surgery, spinal cord tissue was prepared for frozen sections. Positive astrocytic expression was observed with glial fibrillary acidic protein (GFAP) immunohistochemical staining whose proliferation level was represented by gray value, i.e. the higher the gray value was, the less the positive cells were, and growth of positive fibers was observed with a biotin dextran amine histological reaction. Motor function was measured according to BBB scores pre-operatively, as well as at days 1, 7, 14, 21, and 28 post-operatively. RESULTS: Three rats died during experimentation. By random supplement, a total of 18 rats were included. GFAP-positive astrocytes were observed in all the three groups. In the control group, astrocytes were characterized according to active function, hyperplasia, proliferation, hypertrophy, and increasing processes as compared to IN-1 group and IN-1/IN-3 group. Astrocyte hyperplasia represented by gray value in the IN-1 group was less than the control group. Gray value of GFAP-positive products in the IN-1/IN-3 group was higher than other two groups (P < 0.05). Biotin dextran amine tracing demonstrated no corticospinal tract fiber outgrowth following spinal cord injury; the fibers were incapable of passing through the glial scar in the control group. Several fibers were distributed in the proximal scar tissue region in the IN-1 group, and the regenerated fibers were disarranged. Many nerve fibers were distributed throughout the scar tissue, and even several biotin dextran amine-positive fibers were observed at the distal end of the injured segment. Post-operative Basso, Beattie, Bresnahan scores were greater than pre-operative ones, while Basso, Beattie, Bresnahan scores in the IN-1/NT-3 group were significantly greater than the other two groups at days 14, 21, and 28 post-surgery (P < 0.05). CONCLUSION: IN-1, in combination with NT-3, promoted axonal regeneration following spinal cord injury, inhibited the colloidal effect, and enhanced the correlation between proximal and distal processes to recover motor function. The recovery effect of IN-1/NT-3 on motor function was superior that of to IN-1 alone.展开更多
Bone marrow mesenchymal stem cell transplantation has been shown to be therapeutic in the repair of spinal cord injury. However, the low survival rate of transplanted bone marrow mesenchymal stem cells in vivo remains...Bone marrow mesenchymal stem cell transplantation has been shown to be therapeutic in the repair of spinal cord injury. However, the low survival rate of transplanted bone marrow mesenchymal stem cells in vivo remains a problem. Neurotrophin-3 promotes motor neuron survival and it is hypothesized that its transfection can enhance the therapeutic effect. We show that in vitro transfection of neurotrophin-3 gene increases the number of bone marrow mesenchymal stem cells in the region of spinal cord injury. These results indicate that neurotrophin-3 can promote the survival of bone marrow mesenchymal stem cells transplanted into the region of spinal cord injury and potentially enhance the therapeutic effect in the repair of spinal cord injury.展开更多
Schwann cells and neurotrophin-3 play an important role in neural regeneration,but the secretion of neurotrophin-3 from Schwann cells is limited,and exogenous neurotrophin-3 is inactived easily in vivo.In this study,w...Schwann cells and neurotrophin-3 play an important role in neural regeneration,but the secretion of neurotrophin-3 from Schwann cells is limited,and exogenous neurotrophin-3 is inactived easily in vivo.In this study,we have transfected neurotrophin-3 into Schwann cells cultured in vitro using nanoparticle liposomes.Results showed that neurotrophin-3 was successfully transfected into Schwann cells,where it was expressed effectively and steadily.A composite of Schwann cells transfected with neurotrophin-3 and poly(lactic-co-glycolic acid) biodegradable conduits was transplanted into rats to repair 10-mm sciatic nerve defects.Transplantation of the composite scaffold could restore the myoelectricity and wave amplitude of the sciatic nerve by electrophysiological examination,promote nerve axonal and myelin regeneration,and delay apoptosis of spinal motor neurons.Experimental findings indicate that neurotrophin-3 transfected Schwann cells combined with bridge grafting can promote neural regeneration and functional recovery after nerve injury.展开更多
Objective:To investigate the effect of neurotrophin-3 on the expressions of SOD and MDA in the injured spinal cord of rats. Methods: Totally 105 SD rats were randomly divided into 3 groups (n = 35): sham group, contro...Objective:To investigate the effect of neurotrophin-3 on the expressions of SOD and MDA in the injured spinal cord of rats. Methods: Totally 105 SD rats were randomly divided into 3 groups (n = 35): sham group, control group and experimental group. Animal model of acute spinal cord was inflicted with Allen's method by a thin plastic tube situated in subarachnoid space below the injury level for perfusion. Rats in experimental group received 20μl NT-3 (200 ng) from the tube at 0, 4. 8. 12. 24 h and 3. 7 d after injury, and those in control group got the equal volume of normal saline at the same time points. The animals in sham group only received opening vertebral plate and putting tube in subarachnoid space. The rats were sacrificed at 4, 8. 12. 24 h, and 3. 7, 14 d postinjury (n = 5). And the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in blood were observed with colorimetric method. Results: The serum level of SOD reduced obviously and the level of MDA raised obviously in rats after the injury, and the activity of SOD reached the lowest on day 3 and the concentration of MDA reached peak at the 7 d. In the experimental group, the SOD level was obviously higher (P<0. 01). and MDA level was lower than the control (P<0. 01). Conclusion:NT-3 can mitigate secondary injury of spinal cord in vivo. One of mechanisms is that inhibits abnormal expression of MDA and elevates the activity of SOD. thus the injury of free radical and lipid peroxidation is attenuated.展开更多
基金Laboratory Animal Foundation Program of Military,Grant/Award Number:SYDW[2018]01Promotion Plan of the Air Force Medical University,Grant/Award Number:2020SWAQ11Shaanxi Province Innovation Capability Support Plan,Grant/Award Number:2021PT-037。
文摘Traumatic brain injury(TBI)is the main cause of disability,mental health disorder,and even death,with its incidence and social costs rising steadily.Although different treatment strategies have been developed and tested to mitigate neurological decline,a definitive cure for these conditions remains elusive.Studies have revealed that vari-ous neurotrophins represented by the brain-derived neurotrophic factor are the key regulators of neuroinflammation,apoptosis,blood-brain barrier permeability,neurite regeneration,and memory function.These factors are instrumental in alleviating neu-roinflammation and promoting neuroregeneration.In addition,neural stem cells(NSC)contribute to nerve repair through inherent neuroprotective and immunomodulatory properties,the release of neurotrophins,the activation of endogenous NSCs,and in-tercellular signaling.Notably,innovative research proposals are emerging to combine BDNF and NSCs,enabling them to synergistically complement and promote each other in facilitating injury repair and improving neuron differentiation after TBI.In this review,we summarize the mechanism of neurotrophins in promoting neurogen-esis and restoring neural function after TBI,comprehensively explore the potential therapeutic effects of various neurotrophins in basic research on TBI,and investigate their interaction with NSCs.This endeavor aims to provide a valuable insight into the clinical treatment and transformation of neurotrophins in TBI,thereby promoting the progress of TBI therapeutics.
文摘Objective Cloning and sequencing of the human neurotrophin 4 gene.Methods With the chromosomal DNA of human blood lymphocytes as template,hNT 4 coding genes were amplified by polymerase chain reaction and recombinated into phage vector pGEM T Easy,which were sequenced by using Sanger’s single stranded DNA terminal termination method.Results The sequence of the cloned gene is completely the same as that reported in the literature.Conclusion This study successfully cloning and sequenced the gene of mhNT 4,and it would be convenient for us to study the expression of mhNT 4 in eukaryote,and to continue the research on the gene therapy of Alzheimer’s disease intensively.This study indicate that the hNT 4 is conservative in different races and individuals.
基金Supported by Research Grants for Nervous and Mental Disorders from the Ministry of Health,Labor and Welfare Health and Labor Sciences Research Grants (Research on Psychiatric and Neurological Diseases and Mental Health)+2 种基金Health and Labor Sciences Research Grants,a grant from the Japan Foundation for Neuroscience and Mental Healththe Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (Kunugi H)a Grant-in-Aid for Young Scientists (A) (21680034) from the Ministry of Education,Culture,Sports,Science,and Technology of Japan (Numakawa T)
文摘Brain-derived neurotrophic factor(BDNF),a critical neurotrophin,regulates many neuronal aspects including cell differentiation,cell survival,neurotransmission,and synaptic plasticity in the central nervous system(CNS) .Though BDNF has two types of receptors,high affinity tropomyosin-related kinase(Trk) B and low affinity p75 receptors,BDNF positively exerts its biological effects on neurons via activation of TrkB and of resultant intracellular signaling cascades including mitogenactivated protein kinase/extracellular signal-regulated protein kinase,phospholipase Cγ,and phosphoinositide 3-kinase pathways.Notably,it is possible that alteration in the expression and/or function of BDNF in the CNS is involved in the pathophysiology of various brain diseases such as stroke,Parkinson's disease,Alzheimer's disease,and mental disorders.On the other hand,glucocorticoids,stress-induced steroid hormones,also putatively contribute to the pathophysiology of depression.Interestingly,in addition to the reduction in BDNF levels due to increased glucocorticoid exposure,current reports demonstrate possible interactions between glucocorticoids and BDNF-mediated neuronal functions. Other steroid hormones,such as estrogen,are involved in not only sexual differentiation in the brain,but also numerous neuronal events including cell survival and synaptic plasticity.Furthermore,it is well known that estrogen plays a role in the pathophysiology of Parkinson's disease,Alzheimer's disease,and mental illness,while serving to regulate BDNF expression and/or function.Here,we present a broad overview of the current knowledge concerning the association between BDNF expression/function and steroid hormones(glucocorticoids and estrogen).
基金supported by a postdoctoral contract granted by Subprograma Atraccio de Talent-Contractes Postdoctorals de la Universitat de Valencia
文摘The many important benefits of physical exercise also encompass maintenance or improvement of cognitive functions. Among the variousmechanisms underlying the association between physical exercise and brain health, recent evidence attests that neurotrophin receptor signalingmay have an important role, because the activation of this pathway leads to growth and differentiation of new neurons and synapses, supportsaxonal and dendritic growth, fosters synaptic plasticity, and preserves survival of existing neurons. In this review of published evidence, we highlightthat a positive relationship exists between physical exercise and circulating brain-derived neurotrophic factor levels and that the postexercisevariation of this molecule is associated with improvement of neurocognitive functioning. Less clear evidence has instead been published forother neurotrophins, such as nerve growth factor, neurotrophin-3, and neurotrophin-4. Overall, promotion of adequate volumes and intensities ofphysical exercise (i.e., approximately 3 months of moderate-intensity aerobic exercise, with 2—3 sessions/week lasting not less than 30 min)may hence be regarded as an inexpensive and safe strategy for boosting brain-derived neurotrophic factor release, thus preserving or restoringcognitive functions.
文摘The role of neurotrophins in neuronal plasticity has recently become a strong focus in neuroregeneration research field to elucidate the biological mechanisms by which these molecules modulate synapses,modify the response to injury,and alter the adaptation response.Intriguingly,the prior studies highlight the role of p75 neurotrophin receptor(p75^(NTR))in various injuries and diseases such as central nervous system injuries,Alzheimer's disease and amyotrophic lateral sclerosis.More comprehensive elucidation of the mechanisms,and therapies targeting these molecular signaling networks may allow for neuronal tissue regeneration following an injury.Due to a diverse role of the p75^(NTR)in biology,the body of evidence comprising its biological role is diffusely spread out over numerous fields.This review condenses the main evidence of p75^(NTR)for clinical applications and presents new findings from published literature how data mining approach combined with bioinformatic analyses can be utilized to gain new hypotheses in a molecular and network level.
文摘Neurotrophins (NTs) are implicated in the maintenance and survival of the peripheral and central nervous systems and mediate several forms of synaptic plasticity. Members of the family include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NT3, and NT4. NTs were first identified as survival factors for developing neurons, but are pleiotropic molecules that can exert a variety of functions, including the regulation of neuronal differentiation, axonal and dendritic growth, and synaptic plasticity (Bothwell, 2014). NTs interact with two distinct types of receptors: the common p75 neurotrophin receptor, which belongs to the tumor necrosis factor receptor superfamily of death receptors and the Trk receptor tyrosine kinase family.
基金supported by Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica Grants No.216515 and IN 211718。
文摘This manuscript reviews the function and fundamental characteristics of the neurotrophins and their receptors to introduce the reader to the differential effects exhibited by the neurotrophins;brain-derived neurotrophic factor and neurotrophin 4/5 when acted together after sequential presentation.The neurotrophin 4/5 exhibits an inhibitory action on the modulatory effect of brain-derived neurotrophic factor in corticostriatal synapses when they are administered sequentially(brain-derived neurotrophic factor to neurotrophin 4/5).This inhibitory effect has not been previously documented and is relevant for these neurotrophins as both of them stimulate the TrkB receptor.The additive effect of these neurotrophins is also discussed and occurs when neurotrophin 4/5 exposure is followed by brain-derived neurotrophic factor in a mouse model of striatal degeneration.Occlusive and additive effects of both neurotrophins are accompanied by changes in the expression of the TrkB receptor isoforms,specifically TrkB-T1 and TrkB-FL,as well as differences in phosphorylation levels of the TrkB receptor.The results of the experiments described raise several questions to inquire about the role that TrkB-T1 receptor plays in striatal physiology,as well as the functional relevance of the interaction of brain-derived neurotrophic factor and neurotrophin 4/5 in the brain and more specifically at the striatal circuits in normal as well as pathological conditions.
文摘Neurotrophic factors are able to promote neuronalsurvival and prevent neuronal death induced by variousinjuries and have potential uses in the treatment ofneuronal degenerative diseases and neuropathy. Due tothe existence of brain blood barrier, neurotrophic factorscan not be ased in CNS diseases directly. Gene therapy isa good candidate to overcome this problem.
基金a Grant from Department of Health of Hunan Province of China,No.B2005-076
文摘BACKGROUND:Nogo-neutralizing antibody IN-1 accelerates axon growth and enhances recovery of spinal cord function by inhibiting growth inhibitory factors. Neurotrophin-3 (NT-3)contributes to regeneration of nerve fibers in the spinal cord and motor function recovery. The combination of Nogo-neutralizing antibody IN-1 and NT-3 is hypothesized to produce better outcomes and facilitate axonal regeneration by affecting c-Fos and c-Jun protein expression. OBJECTIVE:To investigate the combined effects of Nogo-neutralizing antibody IN-1 and NT-3 on c-Fos and c-Jun protein levels in the injured spinal cord. DESIGN,TIME AND SETTING:A randomized,controlled study was performed at the Laboratory of Neuroanatomy,Xiangya Medical College,Central South University and the Central Laboratory of Third Xiangya Hospital of China from June 2005 to December 2007. MATERIALS:NT-3 (Peprotech,USA) and Nogo-neutralizing antibody IN-1 (Santa Cruz Biotechnology,USA) were used in this study. METHODS:Hemisectioned spinal cord injury models were established by cutting the posterior 2/3 of rat spinal cord,which is equivalent to the T8 level in the human spine. A total of 120 rats were equally and randomly assigned to three groups:model (0.2 μL saline),IN-1 (0.2 μL IN-1),and IN-1/NT-3 (0.2 μL IN-1 + 0.2 μL NT-3). The compounds were separately infused into transection sites on the side of head. MAIN OUTCOME MEASURES:Western blot analysis was employed to measure c-Fos and c-Jun protein expression in the injured spinal cord at 15,30 minutes,1,2,4,6,8,and 12 hours following surgery. RESULTS:Following spinal cord injury,c-Fos and c-Jun protein expression were increased and peaked at 4-6 hours. Following injection of IN-1 or the combination of IN-1 and NT-3,c-Fos protein expression was significantly reduced in the injured spinal cord (P < 0.05 or P < 0.01) (with the exception of the 15 minute time point). However,c-Jun protein expression was significantly increased (P < 0.05 or P < 0.01) (with the exception of the 15 and 30 minute time points). Combined application of IN-1 and NT-3 resulted in significantly altered protein expression compared to IN-1 alone. CONCLUSION:IN-1 increases c-Jun protein levels and protects the injured spinal cord by inhibiting c-Fos protein levels. Moreover,the effects of IN-1 combined with NT-3 are more significant than with IN-1 alone.
基金This project was supported by grants from the Public Health Ministry Research Foundation and Hubei Natural Science Foundation of China (No.97J071)
文摘Bioactive proteins from SD rat limb buds were extracted and purified.Fractions of 22 ku, 34 ku and 95 ku were proved to have neurotrophic activity to neurons, and the combined activity of these three fractions was the highest. So they were combinedly added into the culture medium of sensor neurons in dorsal root ganglia and motor neurons of anterior spinal cord from 2-week-old embryonic rats, and PBS was added as control. Phase-contrast microscopic and electron microscopic observations, and true cholinesterase measurements were performed to evaluate the survival and changes in growth, function, and ultrastructure of these cultured neurons. In the experimental group, it was found that the AchE activity was higher (P【0.01), ultrastructural changes in mitochondria,Gorgi’s complex and other cell organs were milder than those in the control group. The results showed limb buds derived neurotrophins played an important role in maitaining the survival of the neurons and promoting the growth of axons. It was
基金National Natural Science Foundation of China(81900800)Natural Science Basic Research Plan in Shaanxi Province(2019JM-560).
文摘Objective:To study the effect and mechanism of neurotrophin 3 (NT-3) on inhibiting dexamethasone (DEX)-induced mouse MC3T3-E1 osteoblast apoptosis.Methods:Mouse MC3T3-E1 osteoblasts were cultured and divided into groups. Control group were treated with DMEM without drugs, DEX group were treated with DMEM containing 5μmol/L dexamethasone, and NT-3 group were treated with DMEM containing 5μmol/L dexamethasone and 100ng/mL NT-3. Apoptosis rate, proliferation viability, osteogenesis marker contents as well as apoptosis gene and PI3K/AKT/mTOR signaling pathway molecule expression were detected.Results: The apoptosis rate as well as bax and caspase-3 expression in the cells of DEX group was significantly higher than those of control group, whereas proliferation viability value, ALP, OCN and COL-I contents in the medium as well as bcl-2, p-PI3K, p-AKT and p-mTOR expression in the cells were significantly lower than those of control group (P<0.05);the apoptosis rate as well as bax and caspase-3 expression in the cells of NT-3 group was significantly lower than those of DEX group, whereas proliferation viability value, ALP, OCN and COL-I contents in the medium as well as bcl-2, p-PI3K, p-AKT and p-mTOR expression in the cells were significantly higher than those of DEX group (P<0.05).Conclusion:NT-3 has inhibiting effect on the dexamethasone-induced mouse MC3T3-E1 osteoblast apoptosis, and the possible mechanism of this effect is to activate the PI3K/AKT/mTOR signaling pathway.
基金Supported by grants from the National Natural Science Foundation of China(No.ZR2015HM025)Technology Development Program of Shandong Province,China(No.2011YD18003)CSCO-Hengrui Cancer Research Fund(No.Y-HR2018-293 and Y-HR2018-294).
文摘Objective Neurotrophin 3(NTF3)is involved in numerous biological processes;however,its role in hepatocellular carcinoma(HCC)is not well studied.This study investigated NTF3 function in HCC progression and revealed its underlying molecular mechanisms.Methods The prognostic relevance of NTF3 was determined through a bioinformatical analysis of publicly available TCGA data.Immunohistochemistry of HCC biopsies was performed to explore the expression of NTF3.Cell growth and proliferation were analyzed using a Cell Counting Kit-8(CCK-8)assay.Cell invasion and migration were analyzed using Boyden Transwell and wound healing assays.Protein expression and mRNA levels were evaluated through immunoblotting and quantitative polymerase chain reaction(qPCR).Cell apoptosis was evaluated with flow cytometry.Results NTF3 expression was significantly lower in HCC tissues than in adjacent non-tumor tissues.Low NTF3 expression was significantly associated with decreased patient survival and specific clinicopathological features.NTF3 overexpression reduced the proliferation,migration,and invasion abilities of HCC cell lines.Conclusion Decreased expression of NTF3 is associated with poor prognosis in HCC patients,likely due to its action in promoting HCC cell proliferation,migration,and invasion.Our findings provide a novel understanding into the pathogenesis of HCC and the role of NTF3 in tumor progression,suggesting that targeting NTF3 has potential therapeutic and diagnostic value for HCC.
文摘Objective:To investigate the correlation among the expression of neurotrophins (NTs) family and its receptors with cell proliferation and invasion in ovarian cancer.Methods:Ninety patients with ovarian cancer who underwent surgical treatment in Guangyuan First People's Hospital between December 2015 and October 2017 were selected as ovarian cancer group, and 67 patients with ovarian chocolate cyst were selected as benign lesion group. The differences in the expression of NTs family and its receptors, proliferation genes and invasion genes in lesions were compared between the two groups, and Pearson test was used to further evaluate the correlation among the expression of NTs family and its receptors with cancer cell malignancy in ovarian cancer tissue.Results:NT-3 mRNA expression in ovarian cancer group was lower than that in benign lesion group whereas NT-5, TrkA, TrkB and TrkC mRNA expression were higher than those in benign lesion group;proliferation genes FUNDC1, GRP78, PTTG and SMG-1 mRNA expression were higher than those in benign lesion group whereas shSASH1 and ESRP1 mRNA expression were lower than those in benign lesion group;invasion genes Clusterin, EFEMP1, Twist and IFITM1 mRNA expression were higher than those in benign lesion group whereas DUSP10 mRNA expression was lower than that in benign lesion group. Pearson test showed that the NT-5, TrkA, TrkB AND TrkC mRNA expression in ovarian cancer were directly correlated with cancer cell proliferation and invasion activity.Conclusion: The expression levels of NTs family and its receptors are abnormal in ovarian cancer and the specific expression levels are directly correlated with the proliferation and invasion activity of cancer cells.
文摘<正>BACKGROUND:Many methods have been attempted to repair nerves following spinal cord injury, including peripheral nerve transplantation,Schwann cell transplantation,olfactory ensheathing cell transplantation,and embryonic neural tissue transplantation.However,there is a need for improved outcomes. OBJECTIVE:To investigate the repair feasibility for rat spinal cord injury using human neural stem cells(hNSCs) genetically modified by lentivirus to express neurotrophin-3. DESIGN,TIME AND SETTING:In vitro cell biological experiment and in vivo randomized,controlled, genetic engineering experiment were performed at the Third Military Medical University of Chinese PLA and First People's Hospital of Yibin,China from March 2006 to December 2007. MATERIALS:A total of 64 adult,female,Wistar rats were used for the in vivo study.Of them,48 rats were used to establish models of spinal cord hemisection,and were subsequently equally and randomly assigned to model,genetically modified hNSC,and normal hNSC groups.The remaining 16 rats served as normal controls. METHODS:hNSCs were in vitro genetically modified by lentivirus to secrete both green fluorescence protein and neurotrophin-3.Neurotrophin-3 expression was measured by Western blot. Genetically modified hNSC or normal hNSC suspension(5×10~5) was injected into the rat spinal cord following T_(10) spinal cord hemisection.A total of 5μL Dulbecco's-modified Eagle's medium was infused into the rat spinal cord in the model group.Transgene expression and survival of transplanted hNSCs were determined by immunohistochemistry.Motor function was evaluated using the Basso,Beattie,and Bresnahan(BBB) scale. MAIN OUTCOME MEASURES:The following parameters were measured:expression of neurotrophin-3 produced by genetically modified hNSCs,transgene expression and survival of hNSCs in rats,motor function in rats. RESULTS:hNSCs were successfully genetically modified by lentivirus to stably express neurotrophin-3.The transplanted hNSCs primarily gathered at,or around,the injection site two weeks following transplantation,and gradually migrated towards the surrounding tissue. Transplanted hNSCs were observed 7.0-8.0 mm away from the injection site.In addition,hNSCs were observed 10 weeks after transplantation.At week 4,BBB locomotor scores were significantly greater in the genetically modified hNSC and normal hNSC groups,compared with the model group (P<0.05),and scores were significantly greater in the genetically modified hNSC group compared with the normal hNSC group(P<0.05). CONCLUSION:hNSCs were genetically modified with lentivirus to stably secrete neurotrophin-3. hNSCs improved motor function recovery in rats following spinal cord injury.
基金the Foundation of Hunan Public Health Bureau, No.B2005-076
文摘BACKGROUND: Recent studies have suggested that regeneration of the central nerve fiber following spinal cord injury occurs under specific conditions. OBJECTIVE: To study the effects of Nogo-neutralizing antibody (IN-1), in combination with neurotrophin-3 (NT-3), on axonal regeneration and motor function following spinal cord injury in the rat. DESIGN, TIME AND SETTING: A randomized, controlled, animal study combining immunohistochemistry was performed at the Laboratory of Neuroanatomy of Xiangya Medical College, and Central Laboratory of Xiangya the Third Hospital, Central South University from January 2006 to December 2007. MATERIALS: Eighteen healthy, Sprague Dawley rats were randomly divided into three groups, with six rats per group: control, IN-1, and IN-1/NT-3. Hemisectioned spinal cord injury models were established by cutting the posterior 2/3 of spinal cord, which is equivalent to the T8 level. METHODS: A polyethylene tubing was inserted through into subarachnoid cavity, equivalent to the superior margin at the T8 level. Saline, IN-1, and IN-1/NT-3 were respectively injected into control, IN-1, and IN-1/NT-3 groups, three times/day for seven consecutive days. MAIN OUTCOME MEASURES: At 2 weeks post-surgery, biotin dextran amine (10%) was injected into the right sensorimotor cortex area. At day 28 post-surgery, spinal cord tissue was prepared for frozen sections. Positive astrocytic expression was observed with glial fibrillary acidic protein (GFAP) immunohistochemical staining whose proliferation level was represented by gray value, i.e. the higher the gray value was, the less the positive cells were, and growth of positive fibers was observed with a biotin dextran amine histological reaction. Motor function was measured according to BBB scores pre-operatively, as well as at days 1, 7, 14, 21, and 28 post-operatively. RESULTS: Three rats died during experimentation. By random supplement, a total of 18 rats were included. GFAP-positive astrocytes were observed in all the three groups. In the control group, astrocytes were characterized according to active function, hyperplasia, proliferation, hypertrophy, and increasing processes as compared to IN-1 group and IN-1/IN-3 group. Astrocyte hyperplasia represented by gray value in the IN-1 group was less than the control group. Gray value of GFAP-positive products in the IN-1/IN-3 group was higher than other two groups (P < 0.05). Biotin dextran amine tracing demonstrated no corticospinal tract fiber outgrowth following spinal cord injury; the fibers were incapable of passing through the glial scar in the control group. Several fibers were distributed in the proximal scar tissue region in the IN-1 group, and the regenerated fibers were disarranged. Many nerve fibers were distributed throughout the scar tissue, and even several biotin dextran amine-positive fibers were observed at the distal end of the injured segment. Post-operative Basso, Beattie, Bresnahan scores were greater than pre-operative ones, while Basso, Beattie, Bresnahan scores in the IN-1/NT-3 group were significantly greater than the other two groups at days 14, 21, and 28 post-surgery (P < 0.05). CONCLUSION: IN-1, in combination with NT-3, promoted axonal regeneration following spinal cord injury, inhibited the colloidal effect, and enhanced the correlation between proximal and distal processes to recover motor function. The recovery effect of IN-1/NT-3 on motor function was superior that of to IN-1 alone.
基金supported by Scientific Research Fund of Xinxiang Medical University,No.2013ZD120Science and Technology Innovation Talents in Universities in Ministry of Education of Henan Province in 2010,No.2010HASTIT036
文摘Bone marrow mesenchymal stem cell transplantation has been shown to be therapeutic in the repair of spinal cord injury. However, the low survival rate of transplanted bone marrow mesenchymal stem cells in vivo remains a problem. Neurotrophin-3 promotes motor neuron survival and it is hypothesized that its transfection can enhance the therapeutic effect. We show that in vitro transfection of neurotrophin-3 gene increases the number of bone marrow mesenchymal stem cells in the region of spinal cord injury. These results indicate that neurotrophin-3 can promote the survival of bone marrow mesenchymal stem cells transplanted into the region of spinal cord injury and potentially enhance the therapeutic effect in the repair of spinal cord injury.
基金financially supported by the grants for Science and Technology Innovation Talents in Universities in Ministry of Education of Henan Province in 2010,No.2010HASTIT036
文摘Schwann cells and neurotrophin-3 play an important role in neural regeneration,but the secretion of neurotrophin-3 from Schwann cells is limited,and exogenous neurotrophin-3 is inactived easily in vivo.In this study,we have transfected neurotrophin-3 into Schwann cells cultured in vitro using nanoparticle liposomes.Results showed that neurotrophin-3 was successfully transfected into Schwann cells,where it was expressed effectively and steadily.A composite of Schwann cells transfected with neurotrophin-3 and poly(lactic-co-glycolic acid) biodegradable conduits was transplanted into rats to repair 10-mm sciatic nerve defects.Transplantation of the composite scaffold could restore the myoelectricity and wave amplitude of the sciatic nerve by electrophysiological examination,promote nerve axonal and myelin regeneration,and delay apoptosis of spinal motor neurons.Experimental findings indicate that neurotrophin-3 transfected Schwann cells combined with bridge grafting can promote neural regeneration and functional recovery after nerve injury.
文摘Objective:To investigate the effect of neurotrophin-3 on the expressions of SOD and MDA in the injured spinal cord of rats. Methods: Totally 105 SD rats were randomly divided into 3 groups (n = 35): sham group, control group and experimental group. Animal model of acute spinal cord was inflicted with Allen's method by a thin plastic tube situated in subarachnoid space below the injury level for perfusion. Rats in experimental group received 20μl NT-3 (200 ng) from the tube at 0, 4. 8. 12. 24 h and 3. 7 d after injury, and those in control group got the equal volume of normal saline at the same time points. The animals in sham group only received opening vertebral plate and putting tube in subarachnoid space. The rats were sacrificed at 4, 8. 12. 24 h, and 3. 7, 14 d postinjury (n = 5). And the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in blood were observed with colorimetric method. Results: The serum level of SOD reduced obviously and the level of MDA raised obviously in rats after the injury, and the activity of SOD reached the lowest on day 3 and the concentration of MDA reached peak at the 7 d. In the experimental group, the SOD level was obviously higher (P<0. 01). and MDA level was lower than the control (P<0. 01). Conclusion:NT-3 can mitigate secondary injury of spinal cord in vivo. One of mechanisms is that inhibits abnormal expression of MDA and elevates the activity of SOD. thus the injury of free radical and lipid peroxidation is attenuated.
