• Journal of Korean Neurosurgical Society
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• v.53 no.2
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• pp.65-71
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• 2013

Objective : In order to develop a novel nerve guidance channel using porcine small intestinal submucosa (SIS) for nerve regeneration, we investigated the possibility of SIS, a tissue consisting of acellular collagen material without cellular immunogenicity, and containing many kinds of growth factors, as a natural material with a new bioactive functionality. Methods : Left sciatic nerves were cut 5 mm in length, in 14 Sprague-Dawley rats. Grafts between the cut nerve ends were performed with a silicone tube (Silicon group, n=7) and rolled porcine SIS (SIS group, n=7). All rats underwent a motor function test and an electromyography (EMG) study on 4 and 10 weeks after grafting. After last EMG studies, the grafts, including proximal and distal nerve segments, were retrieved for histological analysis. Results : Foot ulcers, due to hypesthesia, were fewer in SIS group than in Silicon group. The run time tests for motor function study were 2.67 seconds in Silicon group and 5.92 seconds in SIS group. Rats in SIS group showed a better EMG response for distal motor latency and amplitude than in Silicon group. Histologically, all grafts contained some axons and myelination. However, the number of axons and the degree of myelination were significantly higher in SIS group than Silicon group. Conclusion : These results show that the porcine SIS was an excellent option as a natural biomaterial for peripheral nerve regeneration since this material contains many kinds of nerve growth factors. Furthermore, it could be used as a biocompatible barrier covering neural tissue.

• Biotechnology and Bioprocess Engineering:BBE
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• v.3 no.2
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• pp.51-54
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• 1998

It has been proved that co-cultivation of human neroblastoma cells and human fibroblast cells can enhance nerve cell growth and the production of BDNF in perfusion cultivation. In batch co-cultivation, maximum cell density was increased up to 1.76${\times}$106 viable cells/mL from 9${\times}$105 viable cells/mL of only neuroblastoma cell culture. The growth of neuroblastoma cells was greatly improved by culturing both nerve and fibroblast cells in a perfusion process, maintaining 1.5${\times}$106 viable cells/mL, which was much higher than that form fed-batch cultivation. The nerve cell growth was greatly enhance in both fed-batch and perfusion cultivations while the growth of fibroblast cells was not. It strongly implies that the factors secreted from human fibrobast cells and/or the environments of co-culture system can enhance both cell growth and BDNF secretion. Specific BDNF production rate was not enhanced in co-cultures; however, the production period was increased as the cell growth was lengthened in the co-culture case. Competitive growth between nerve cells and fibroblast cells was not observed in all cases, showing no changes of fibroblast cell growth and only enhancement of the neuroblastoma cell growth and overall BDNF production. It was also found that the perfusion cultivation was the most appropriate process for cultivating two cell lines simultaneously in a bioreactor.

• Archives of Pharmacal Research
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• v.22 no.2
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• pp.108-112
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• 1999

Recombinant murine stem cell factor (rmSCF) or recombinant murine nerve growth factor (rmNGF) induced the morphological change of large numbers of rat peritoneal mast cells (RPMC). We investigated the role of phosphatidylinositol $3^{l}-kinase$ (PI3-kinase) in receptors-mediated morphological change in RPMC. Exposure of RPMC to PI3-kinase inhibitor, wortmannin, before the addition of rmSCF and rmNGF antagonized those factors-induced morphological change. These results suggest that the PI3-kinase is involved in the signal transduction pathway responsible for morphological change following stimulation of rmSCF and rmNGF and that wortmannin blocks these responses.

• Journal of Life Science
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• v.16 no.3 s.76
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• pp.464-471
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• 2006

Peripheral nerve injuries are a commonly encountered clinical problem and often result in severe functional deficits. In the present study, the effects of treadmill exercise on neurotrophin expressions and functional recovery following sciatic crushed nerve injury were investigated. Animals were randomly assigned into four groups: the sciatic nerve injury group, the sciatic nerve injury and 3-day-exercise, the sciatic nerve injury and 7-days-exercise, and the sciatic nerve injury and 14-days-exercise groups. Sciatic nerve injury was caused by crushing the right sciatic nerve for 30 s using a surgical clip. A the light-exercise was applied to each of the exercise group over the respective number of days. In the present results, we identified enhanced axonal re-growth in the distal stump of the sciatic nerve 3-14 days after crush injury with treadmill training. Dorsal root ganglion (DRG) neuron when cultured from animals with nerve injury and treadmill training showed more enhanced neurite outgrowth than that of sedentary animals. Nerve growth factor (NGF) protein levels in low-intensity treadmill training group were highly induced in the injured sciatic nerves 3, 7 and 14 days after injury compared with sedentary group, and brain-derived neurotrophin factor (BDNF) protein levels in treadmill exercise group were highly induced in the injured sciatic nerve 3 days after injury compared with sedentary group. Then, treadmill exercise increased neurotrophic factors induced in the regenerating nerves. We further demonstrate that motor functional recovery after sciatic nerve injury was promoted by treadmill exercise. Thus, the present data provide a new evidence that treadmill exercise enhanced neurotrophins expression and axonal regeneration after sciatic nerve injury in rats.

• BMB Reports
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• v.33 no.6
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• pp.525-530
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• 2000

The nerve growth factor (NGF) induces neuronal differentiation and neurite outgrowth of PC12 cells, whereas epidermal growth factors (EGF) stimulate growth and proliferation of the cells. In spite of this difference, NGF-or EGF-treated PC12 cells share various properties in cellular-signaling pathways. These include the activation of the phosphoinositide (PI)-3 kinase, 70 kDa S6 kinase, and in the mitogen-activated protein (MAP) kinase pathway, following the binding of these growth factors to intrinsic receptor tyrosine kinases (RTKs). Therefore, many studies have been attempted to access the critical signaling events in determining the differentiation and proliferation of PC12 cells. In this study, we investigated the cytosolic phospholipase $A_2$ ($cPLA_2$) in neurite behavior in order to identify the differences of signaling pathways between the NGF-induced differentiation and the EGF-induced proliferation of PC12 cells. We have showed here that the $cPLA_2$ was translocated from cytosol to membrane only in NGF-treated cells. We also demonstrated that this translocation is associated with NGF-induced activation of phospholipase $C-{\gamma}(PLC-{\gamma})$, which elevates intracellular $Ca^{2+}$ concentration. These results reveal that the translocation of $cPLA_2$ may be a requisite event in the neuronal differentiation of PC12 cells. Various phospholipase inhibitors were used to confirm the importance of these enzymes in the differentiation of PC12 cells. Neomycin B, a PLC inhibitor, dramatically inhibited the neurite outgrowth, and two distinct $PLA_2$ inhibitors, 4-bromophenacyl bromide (BPB) and arachidonyltrifluoro-methyl ketone ($AACOCF_3$) also suppressed the neurite outgrowth of the cells, as well Taken together, these data indicated that $cPLA_2$ is involved in NGF-induced neuronal differentiation and neurite outgrowth of PC12 cells.

• Journal of Haehwa Medicine
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• v.14 no.2
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• pp.107-112
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• 2005

Peripheral axons in vertebrate animals can regenerate after nerve injury and accomplish its functional recovery. Numerous studies have revealed that diverse molecular factors are induced during axonal regeneration and their potential roles in axonal regeneration have been studied. Examples is N-CAM, L1, P0, nerve growth factors, GAP-43 and so forth. However, most of the studies on axonal regeneration have been primarily focused on axon fiber regrowth and elucidating molecular factors, and relatively less is known about functional recovery. Also, specific drugs or drug components used in the oriental medicine in relation to nerve fiber regeneration have not been known. And thus, in the present, a study on the effect of Samul-tang components and Samul-tang extracts to regeneration of peripheral axon fiber is underway by immunofluorescence staining. Therefore, this prior application of Samul-tang with documents consideration is reported with a plea for further investigation.

• Polymer(Korea)
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• v.25 no.6
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• pp.893-901
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• 2001

We developed the nerve growth factor (NGF) loaded poly (L - lactide) (PLA) scaffolds by means of emulsion freeze drying method to the possibility for the application of the nerve regeneration of spinal cord disease and the degeneration in Alzheimer's disease. The release amount of NGF from NGF loaded PLA scaffold were analyzed over a 4 week period in vitro at phosphate buffered saline (PBS), pH 7.4, at $37^{\circ}C$. It can be observed the open cell pore structure of porous scaffolds and can be easily controlled the pore structure by the controlling of formulation factors resulting in the controlling of the release rate and the release period. The stability of NGF during the preparation of PLA scaffold was evaluated by comparing the released amounts of total NGF, assayed NGF enzyme - linked immunosorbent assay (ELISA). Released NGF has been found to enhance the neurite sprouting and outgrowth from pheochromocytoma (PC-12) cells. These results suggest that the released NGF from NGF loaded PLA scaffold such as conduit type can be very useful for the nerve regeneration in the neural tissue engineering area.

• BMB Reports
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• v.57 no.4
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• pp.167-175
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• 2024

Cancer progression is driven by genetic mutations, environmental factors, and intricate interactions within the tumor microenvironment (TME). The TME comprises of diverse cell types, such as cancer cells, immune cells, stromal cells, and neuronal cells. These cells mutually influence each other through various factors, including cytokines, vascular perfusion, and matrix stiffness. In the initial or developmental stage of cancer, neurotrophic factors such as nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor are associated with poor prognosis of various cancers by communicating with cancer cells, immune cells, and peripheral nerves within the TME. Over the past decade, research has been conducted to prevent cancer growth by controlling the activation of neurotrophic factors within tumors, exhibiting a novel attemt in cancer treatment with promising results. More recently, research focusing on controlling cancer growth through regulation of the autonomic nervous system, including the sympathetic and parasympathetic nervous systems, has gained significant attention. Sympathetic signaling predominantly promotes tumor progression, while the role of parasympathetic signaling varies among different cancer types. Neurotransmitters released from these signalings can directly or indirectly affect tumor cells or immune cells within the TME. Additionally, sensory nerve significantly promotes cancer progression. In the advanced stage of cancer, cancer-associated cachexia occurs, characterized by tissue wasting and reduced quality of life. This process involves the pathways via brainstem growth and differentiation factor 15-glial cell line-derived neurotrophic factor receptor alpha-like signaling and hypothalamic proopiomelanocortin neurons. Our review highlights the critical role of neurotrophic factors as well as central nervous system on the progression of cancer, offering promising avenues for targeted therapeutic strategies.

• Journal of Life Science
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• v.20 no.6
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• pp.948-954
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• 2010

Exercise can favorably influence brain plasticity by facilitating neurogeneration, neuroadaptivity, and neuroprotection. Aerobic exercise has been reported to change brain nerve growth factors (growth hormone, insulin like factor-1, estrogen and serotonin). The purpose of this study was to demonstrate the effects of aerobic exercise for 12 weeks on brain nerve growth factors in girls. Fourteen female participants in elementary school grades 1 through 3 were randomly allocated to the exercise group (EG, n=6) and control group (CG, n=8). The EG participated in 60 minutes of modified ballet exercise as aerobic training three days a week for 12 weeks. Based on comparison between groups by two-way ANOVA with repeated measures, aerobic exercise program participants experienced decreased weight (p<0.01), BMI (p<0.01), fat mass (p<0.001), fat percent (p<0.001) and increased LBM (lean body mass) percent (p<0.001). In addition, we detected that aerobic exercise decreased the level of serotonin (p<0.05) and increased the level of GH (p<0.05) and IGF-1 (p<0.05). These findings suggest that aerobic exercise programs can be an efficient intervention to change body composition, alleviate central fatigue, improve brain function, and induce brain cell proliferation in girls.

• Journal of Life Science
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• v.22 no.5
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• pp.569-574
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• 2012

This study was conducted to investigate the effect of exercise on oxidative stress, nerve growth, and hepatocyte growth factors in obese children. After 12 weeks of aerobic exercise training, the aforementioned parameters before and after the training were compared. As a result, the nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were shown to be lower in the OT than in the NT before and after the training, respectively ($p$ <0.05). The NGF was shown to have increased in both groups after the training ($p$ <0.05). The hepatocyte growth factor (HGF) was shown to be higher in the OT than in the NT before the training ($p$ <0.05), with no difference found afterwards. The malondialdehyde (MDA), ox-LDL, and 8-OHdG (Oxo-2'-deoxyguanosine) were shown to be higher in the OT than in the NT ($p$ <0.05). For ox-LDL, a difference was found between before and after the training ($p$ <0.05). The results of this study showed that obesity induced oxidative stress and caused the abnormalities of nerve and HGF secretion in obese children, and that the 12 weeks of aerobic exercise increased NGF levels, thereby promoting the development of neurogenesis in children.