OBJECTIVEThis research aims to study the changes in pain threshold and glial cell line-derived neurotrophic factor (GDNF) in a Sprague Dawley (SD) rat model oftrigeminal neuralgia.

METHODSA total of 36 male SD rats were randomly divided into three groups: operative, sham-operative, and control. In the operative group, a chronic constriction injury (CCI) was caused by placing loose chromic gut ligatures around the right infraorbital nerve (ION). In the sham-operative group, the right ION was subjected to the same procedure, but without ligation. In the control group, the right ION was not subjected to any treatment. The pain thresholds of the three groups were recorded at different times after the operation. The GDNF expression in each group was analyzed via immunohistochemical staining.

RESULTSAn allodynia to mechanical stimulation in the region of the ligated ION was observed starting on the 2nd week after operation. Pain thresholds started to increase gradually from the 6th week and returned to the original level at the 10th to 12th week after operation. Cells that expressed the GDNF markedly increased in number in the operative group with changes observed at different times.

CONCLUSIONWe use chronic constriction injury to the infraorbital nerve (CCI-ION) to establish a trigeminal neuralgia-like animal model in SD rats. GDNF may play a role in regulating pain by promoting the restoration and regeneration of nerve fibers.

Animals ; Constriction ; Disease Models, Animal ; Glial Cell Line-Derived Neurotrophic Factor ; Glial Cell Line-Derived Neurotrophic Factors ; Hyperalgesia ; Male ; Pain Threshold ; Rats ; Rats, Sprague-Dawley ; Trigeminal Neuralgia

Vectors used to carry foreign genes play an important role in gene therapy, among which, the adeno-associated virus (AAV) has many advantages, such as nonpathogenicity, low immunogenicity, stable and long-term expression and multiple-tissue-type infection, etc. These advantages have made AAV one of the most potential vectors in gene therapy, and widely used in many clinical researches, for example, Parkinson's disease. This paper introduces the biological characteristics of AAV and the latest research progress of AAV carrying neurotrophic factor, dopamine synthesis related enzymes and glutamic acid decarboxylase gene in the gene therapy of Parkinson's disease.
Animals ; Aromatic-L-Amino-Acid Decarboxylases ; genetics ; Dependovirus ; genetics ; Gene Transfer Techniques ; Genetic Therapy ; Genetic Vectors ; Glial Cell Line-Derived Neurotrophic Factor ; genetics ; Glutamate Decarboxylase ; genetics ; Humans ; Nerve Growth Factors ; genetics ; Neurturin ; genetics ; Parkinson Disease ; therapy

OBJECTIVE: Cellular diversity in the mammalian central nervous system is originated from precursor cells present in the neural ectoderm. The multipotent neural stem cells(NSCs) rapidly proliferate to give rise to transiently dividing progenitors that eventually differentiate into several cell types of neural cells. The authors investigate whether NSCs could differentiate neurons and glia and express neurotrophic factor. METHODS: To establish human neural cell lines, we isolated neural stem cells from human fetal telencephalon. Secondly, to investigate the expression of neurotrophic factor, basic fibroblast growth factor(bFGF), brain-derived neurotrophic factor(BDNF) and glial derived neurotrophic factor(GDNF) in rat and human cell, mRNA expressions of bFGF, BDNF and GDNF were detected by the reverse transcripted polymerase chain reaction(RT-PCR) analysis. RESULTS: In the NSCs cultures of embryonic rat striata and human fetal telencephalon, we demonstrated that bFGF induces the proliferation of stem cell, which give rise to spheres of undifferentiated cell that generate neurons and glia. Also, neurotrophic factor transcripts were identified using PCR in rat and human NSCs. CONCLUSION: These results demonstrate that human NSCs derived from human fetal telencephalon could differentiate neurons and glia and express neurotrophic factors. Therefore, NSCs may be an important key for the therapeutic application of neurotrophic factors.
Animals ; Brain-Derived Neurotrophic Factor ; Cell Line ; Central Nervous System ; Ectoderm ; Fibroblasts ; Glial Cell Line-Derived Neurotrophic Factor ; Humans* ; Nerve Growth Factors* ; Neural Stem Cells* ; Neuroglia ; Neurons ; Polymerase Chain Reaction ; Rats ; RNA, Messenger* ; Stem Cells ; Telencephalon*

BACKGROUND AND OBJECTIVES: The object of this study was to evaluate the effect of platelet rich plasma (PRP) on facial nerve regeneration from an axotomy injury in the guinea pig model. MATERIALS AND METHOD: Experiments involved the transection and repair of right facial nerve. The right facial nerve of 14 albino guinea pigs were completely transected and immediately sutured, followed by fibrin glue only (control group) or fibrin glue +PRP (PRP group). Western blot assay was used to detect neurotrophic factors secreted by PRP. Nerve regeneration was assessed by motor function, electrophysiology, and histology studies. RESULTS: High levels of neurotrophin-3, angiopoietin-1, glial cell line derived neurotrophic factors, nerve growth factors and brain derived neurotrophic factors were demonstrated in PRP. Motor function recovery, compound motor action potentials, and axon count showed significant improvement in guinea pig treated with PRP. CONCLUSION: There was an improved functional outcome with the use of PRP in comparison with control. The increased nerve regeneration found in this study may be due to the neurotrophic factors secreted by PRP.
Action Potentials ; Angiopoietin-1 ; Animals ; Axons ; Axotomy ; Blood Platelets ; Blotting, Western ; Brain-Derived Neurotrophic Factor ; Electrophysiology ; Facial Nerve ; Fibrin Tissue Adhesive ; Glial Cell Line-Derived Neurotrophic Factor ; Glial Cell Line-Derived Neurotrophic Factors ; Guinea Pigs ; Nerve Growth Factor ; Nerve Growth Factors ; Nerve Regeneration ; Platelet-Rich Plasma ; Recovery of Function ; Regeneration

The neurotrophin and glial cell line-derived neurotrophic factor (GDNF) family of growth factors have been extensively studied because of their proven ability to regulate development of the peripheral nervous system. The neurotrophin family, which includes nerve growth factor (NGF), NT-3, NT4/5 and BDNF, is also known for its ability to regulate the function of adult sensory neurons. Until recently, little was known concerning the role of the GNDF-family (that includes GDNF, artemin, neurturin and persephin) in adult sensory neuron function. Here we describe recent data that indicates that the GDNF family can regulate sensory neuron function, that some of its members are elevated in inflammatory pain models and that application of these growth factors produces pain in vivo. Finally we discuss how these two families of growth factors may converge on a single membrane receptor, TRPV1, to produce long-lasting hyperalgesia.
Animals ; Glial Cell Line-Derived Neurotrophic Factors ; physiology ; Humans ; Hyperalgesia ; physiopathology ; Nerve Tissue Proteins ; physiology ; Neurturin ; physiology ; Nociceptors ; cytology ; TRPV Cation Channels ; physiology

Parkinson's disease is the second most common neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons and a biochemical reduction of striatal dopamine levels. Despite the lack of fully understanding of the etiology of Parkinson's disease, accumulating evidences suggest that Parkinson's disease may be caused by the insufficient support of neurotrophic factors, and by microglial activation, resident immune cells in the brain. Naringin, a major flavonone glycoside in grapefruits and citrus fruits, is considered as a protective agent against neurodegenerative diseases because it can induce not only anti-oxidant effects but also neuroprotective effects by the activation of anti-apoptotic pathways and the induction of neurotrophic factors such as brain-derived neurotrophic factor and vascular endothelial growth factor. We have recently reported that naringin has neuroprotective effects in a neurotoxin model of Parkinson's disease. Our observations show that intraperitoneal injection of naringin induces increases in glial cell line-derived neurotrophic factor expression and mammalian target of rapamycin complex 1 activity in dopaminergic neurons of rat brains with anti-inflammatory effects. Moreover, the production of glial cell line-derived neurotrophic factor by naringin treatment contributes to the protection of the nigrostriatal dopaminergic projection in a neurotoxin model of Parkinson's disease. Although the effects of naringin on the nigrostriatal dopaminergic system in human brains are largely unknown, these results suggest that naringin may be a beneficial natural product for the prevention of dopaminergic degeneration in the adult brain.
Adult ; Animals ; Antioxidants ; Brain ; Brain-Derived Neurotrophic Factor ; Citrus ; Citrus paradisi ; Dopamine ; Dopaminergic Neurons ; Glial Cell Line-Derived Neurotrophic Factor ; Humans ; Injections, Intraperitoneal ; Nerve Growth Factors ; Neurodegenerative Diseases ; Neuroprotective Agents ; Parkinson Disease ; Rats ; Sirolimus ; Vascular Endothelial Growth Factor A

STUDY DESIGN: Experimental, prospective study OBJECTIVES: To examine the changes in the variable factors after an acute spinal cord injury(SCI) in rats and dogs simultaneously. SUMMARY OF LITERATURE REVIEW: No study has examined the variations of several factors in a SCI model in different species. MATERIALS AND METHODS: In rats, a laminectomy was performed at the T10 level and the injured spinal cord was extracted. In Beagle dogs, the laminectomy level was T10 and T11. The motor function was evaluated using a modified Tarlov's scale. A RT2 profiler PCR array was used to examine each factor (inflammatory cytokines, factors-related with apoptosis, neurotrophic factors, factors-related with extraceullar matrix). RESULTS: IL-2, TNF, TNFRSF11B increased with time and showed no statistical difference between two species, but TNFSF13B showed a significant difference. BDNF decreased with time in both species, and GDNF was significantly lower in dogs. NGFbeta, CTNF and its receptors showed no significant changes in the two species. MMP1 increased in both species but MMP7 decreased in rats and increased in dogs with time, and showed a significant difference between species. CONCLUSION: The change in inflammatory cytokines and extracellular matrix correlates with each factor in the combined patterns. Moreover, during the first week after SCI, inflammatory cytokines, apoptosis, neutrophic factors, and extracellular matrix factors may show a partial difference between experimental animals, which means that an animal model can be selected according to the particular experimental plan.
Animals ; Apoptosis ; Brain-Derived Neurotrophic Factor ; Cytokines ; Dogs ; Extracellular Matrix ; Glial Cell Line-Derived Neurotrophic Factor ; Interleukin-2 ; Laminectomy ; Models, Animal ; Nerve Growth Factors ; Polymerase Chain Reaction ; Prospective Studies ; Rats ; Spinal Cord ; Spinal Cord Injuries

OBJECTIVE: The association of neurotrophic factors with the etiology of schizophrenia has been widely studied. Among them, glial cell line-derived neurotrophic factor (GDNF) is known to promote the survival and differentiation of dopaminergic neurons. Considering dopamine hypothesis and neurodevelopmental theory, GDNF gene may be related with schizophrenia. In this study, we tried to clarify the association between schizophrenia and GDNF gene polymorphism. METHODS: Genotype and allele frequencies in the promoter and intron regions of GDNF gene were studied by using restriction fragment length polymorphism to compare 180 Korean schizophrenics with 105 Korean controls. RESULTS: We found significant differences between the schizophrenics and the controls in genotype and allele frequencies of BsaI polymorphism in the promoter region of GDNF gene (x2=18.208, df=2, p=0.0001/x2=11.264, df=1, p=0.0008). But no significant differences were found in intron region (p=0.06, p=0.984). CONCLUSION: These results suggest that polymorphism of GDNF gene might be related to the pathogenesis of schizophrenia.
Dopamine ; Dopaminergic Neurons ; Gene Frequency ; Genotype ; Glial Cell Line-Derived Neurotrophic Factor* ; Introns ; Nerve Growth Factors ; Polymorphism, Restriction Fragment Length ; Promoter Regions, Genetic ; Schizophrenia

PURPOSE: To evaluate the expression of glial cell line-derived neurotrophic factor (GDNF) and its receptor, GDNF family receptor alpha subunit 1 (GFRα-1) in the pelvic (middle third) vagina and, particularly, in the paravaginal ganglia of nulliparous and primiparous rabbits. METHODS: Chinchilla-breed female rabbits were used. Primiparas were killed on postpartum day 3 and nulliparas upon reaching a similar age. The vaginal tracts were processed for histological analyses or frozen for Western blot assays. We measured the ganglionic area, the Abercrombie-corrected number of paravaginal neurons, the cross-sectional area of the neuronal somata, and the number of satellite glial cells (SGCs) per neuron. The relative expression of both GDNF and GFRα-1 were assessed by Western blotting, and the immunostaining was semiquantitated. Unpaired two-tailed Student t -test or Wilcoxon test was used to identify statistically significant differences (P≤0.05) between the groups. RESULTS: Our findings demonstrated that the ganglionic area, neuronal soma size, Abercrombie-corrected number of neurons, and number of SGCs per neuron were similar in nulliparas and primiparas. The relative expression of both GDNF and GFRα-1 was similar. Immunostaining for both GDNF and GFRα-1 was observed in several vaginal layers, and no differences were detected regarding GDNF and GFRα-1 immunostaining between the 2 groups. In the paravaginal ganglia, the expression of GDNF was increased in neurons, while that of GFRα-1 was augmented in the SGCs of primiparous rabbits. CONCLUSIONS: The present findings suggest an ongoing regenerative process related to the recovery of neuronal soma size in the paravaginal ganglia, in which GDNF and GFRα-1 could be involved in cross-talk between neurons and SGCs.
Blotting, Western ; Carisoprodol ; Female ; Ganglia ; Ganglion Cysts ; Glial Cell Line-Derived Neurotrophic Factor ; Humans ; Nerve Growth Factors ; Neuroglia ; Neuronal Plasticity ; Neurons ; Postpartum Period ; Rabbits ; Reproduction ; Vagina

The effects of fetal mesencephalic cell grafts on the restoration of nigrostriatal dopaminergic function were studied in the intrastriatal 6-hydroxydopamine-lesioned rats. Four weeks after lesioning, transplantation of ventral mesencephalic cells from embryonic day 14 fetuses showed the number of tyrosine hydroxylase (TH) positive cells and fiber outgrowth in the grafted striatum, and significantly ameliorated symptomatic motor behavior of the animals, as determined by apomorphine-induced rotation. Furthermore, in substantia nigra pars compacta (SNc), the numbers of TH cells and fibers were markedly restored. Dopamine content of ipsilateral SNc was close to that of contralateral SNc (91.9 9.8%) in the transplanted animals, while the ratio was approximately 32% in sham-grafted animals. These results indicate that grafted cells restored the activity for the dopaminergic neurons located in SNc, although they were transplanted into striatum. In addition, we showed that the implanted fetal cells expressed high level of glial cell line-derived neurotrophic factor (GDNF), suggesting that the transplanted fetal cells might serve as a dopamine producer and a reservoir of neurotrophic factors. These results may be helpful in consideration of the therapeutic transplantation at early stage of PD.
Animals ; Dopamine ; Dopaminergic Neurons ; Fetus ; Glial Cell Line-Derived Neurotrophic Factor ; Nerve Growth Factors ; Oxidopamine ; Parkinson Disease ; Rats* ; Substantia Nigra ; Transplantation ; Transplants* ; Tyrosine 3-Monooxygenase