Increased Urinary Nerve Growth Factor as a Predictor of Persistent Detrusor Overactivity After Bladder Outlet Obstruction Relief in a Rat Model

Lee, S.R.,Hong, C.H.,Choi, Y.D.,Kim, J.H. Williams and Wilkins Co 2010 The Journal of urology Vol.183 No.6

Purpose: We evaluated urinary nerve growth factor as a predictive factor for persistent detrusor overactivity after bladder outlet obstruction relief in a rat model. Materials and Methods: A total of 50 female Sprague-Dawley®(TM) rats were divided into 2 groups, including 10 sham operated controls and 40 with bladder outlet obstruction. Obstruction was induced by partial urethral ligation and relieved by ligation removal after 3 weeks. Voided urine was collected before bladder outlet obstruction at time 1, 3 weeks after obstruction onset at time 2 and 3 weeks after obstruction relief at time 3. Cystometry was done in awake rats at times 2 and 3. Bladder tissue was harvested at time 3. Urinary and bladder tissue nerve growth factor was measured by enzyme-linked immunosorbent assay with results adjusted based on creatinine concentration. Results: In 16 rats in which detrusor overactivity disappeared after bladder outlet obstruction relief (group 1) urinary nerve growth factor/creatinine significantly increased from time 1 to 2 and significantly decreased from time 2 to 3 (p = 0.001 and 0.003, respectively). In 8 rats with persistent detrusor overactivity despite obstruction removal (group 2) urinary nerve growth factor/creatinine significantly increased from time 1 to 2 but did not change from time 2 to 3 (p = 0.012 and 0.123, respectively). These rats with persistent detrusor overactivity also had significantly higher urinary nerve growth factor/creatinine at time 1 than controls and group 1 (p = 0.015 and 0.005, respectively). Conclusions: Changes in urinary nerve growth factor may reflect detrusor overactivity, as diagnosed on 2 consecutive cystometries. Increased urinary nerve growth factor before bladder outlet obstruction may predict persistent detrusor overactivity after obstruction relief.

Acidic fibroblast growth factor가 신경재생에 미치는 영향에 관한 실험적 연구

최성원(Sung Weon Choi),권종진(Jong Jin Kwon) 대한구강악안면외과학회 1997 대한구강악안면외과학회지 Vol.23 No.2

Fibroblast growth factor (FGF) is a well-known angiogenic factor and mitogen for endothelial cells, fibroblasts, and Schwann cells. An experimental study on the sciatic nerve of rat was performed to evaluate the effect and to determine the optimal concentration of exogenously-applied aFGF on nerve regeneration. Sixty adult male Sprague-Dawley rats weighing between 200 and 250 gm were divided into control group and 3 experimental groups. The experimental groups were further divided into 0.25 ug/ml, 2.5 ug/ml, and 25 ug/ml aFGF group. 10 mm segmental defect was made at right sciatic nerve and both nerve ends was connected with the polyethylene tube into which aFGF-collagen solution was instilled. After 2, 4, 8 weeks, control and 3 experimental groups were examined by clinical appearance, electrophysiological assessment, and morphologic findings using light microscope, electron microscope, and image analyzer at mid-chamber cross section. The results were as follows. 1. Nerve regeneration was seen in Group 2 (2.5 ug/ml aFGF) and Group 3 (25 ug/ml aFGF) at 2 weeks and the diameter of middle regeneration part of 3 experimental groups was larger than that of control group (p<0.05). 2. There were little differences in latency and amplitude among each group (p>0.05). 3. At 4 weeks, the diameter of myelinated nerve fiber and the thickness of myelin of 3 experimental groups at 4 weeks were larger than those of control group (p<0.05). At 8 weeks, the diameter of myelinated nerve fiber and the thickness of myelin of Group 2 (2.5 ug/ml aFGF) were larger than those of other experimental groups (p<0.05). These results suggest that aFGF enhance peripheral nerve regeneration and nerve regeneration of 2.5 ug/ml aFGF group (Group 2) is more effective than that of any other groups. But, the high concentration of aFGF may not necessarily enhance nerve regeneration. We conclude that it is necessary to examine further long term study for determining optimal concentration of aFGF.

Controlled release of nerve growth factor from heparin-conjugated fibrin gel within the nerve growth factor-delivering implant

Jin-Yong Lee,Soung-Min Kim,Myung-Jin Kim,Jong-Ho Lee 대한구강악안면외과학회 2014 대한구강악안면외과학회지 Vol.40 No.1

Objectives: Although nerve growth factor (NGF) could promote the functional regeneration of an injured peripheral nerve, it is very difficult for NGF to sustain the therapeutic dose in the defect due to its short half-life. In this study, we loaded the NGF-bound heparin-conjugated fibrin (HCF) gel in the NGF-delivering implants and analyzed the time-dependent release of NGF and its bioactivity to evaluate the clinical effectiveness. Materials and Methods: NGF solution was made of 1.0 mg of NGF and 1.0 mL of phosphate buffered saline (PBS). Experimental group A consisted of three implants, in which 0.25 μL of NGF solution, 0.75 μL of HCF, 1.0 μL of fibrinogen and 2.0 μL of thrombin was injected via apex hole with micropipette and gelated, were put into the centrifuge tube. Three implants of experimental group B were prepared with the mixture of 0.5 μL of NGF solution, 0.5 μL HCF, 1.0 μL of fibrinogen and 2.0 μL of thrombin. These six centrifuge tubes were filled with 1.0 mL of PBS and stirred in the waterfilled beaker at 50 rpm. At 1, 3, 5, 7, 10, and 14 days, 1.0 mL of solution in each tubes was collected and preserved at -20 o C with adding same amount of fresh PBS. Enzyme-linked immunosorbent assay (ELISA) was done to determine in vitro release profile of NGF and its bioactivity was evaluated with neural differentiation of pheochromocytoma (PC12) cells. Results: The average concentration of released NGF in the group A and B increased for the first 5 days and then gradually decreased. Almost all of NGF was released during 10 days. Released NGF from two groups could promote neural differentiation and neurite outgrowth of PC12 cells and these bioactivity was maintained over 14 days. Conclusion: Controlled release system using NGF-HCF gel via NGF-delivering implant could be an another vehicle of delivering NGF to promote the nerve regeneration of dental implant related nerve damage .

Early expressions of hypoxia-inducible factor 1alpha and vascular endothelial growth factor increase the neuronal plasticity of activated endogenous neural stem cells after focal cerebral ischemia

Song, Seung,Park, Jong-Tae,Na, Joo Young,Park, Man-Seok,Lee, Jeong-Kil,Lee, Min-Cheol,Kim, Hyung-Seok Medknow PublicationsMedia Pvt Ltd 2014 Neural regeneration research Vol.9 No.9

<P>Endogenous neural stem cells become “activated” after neuronal injury, but the activation sequence and fate of endogenous neural stem cells in focal cerebral ischemia model are little known. We evaluated the relationships between neural stem cells and hypoxia-inducible factor-1α and vascular endothelial growth factor expression in a photothromobotic rat stroke model using immunohistochemistry and western blot analysis. We also evaluated the chronological changes of neural stem cells by 5-bromo-2′-deoxyuridine (BrdU) incorporation. Hypoxia-inducible factor-1α expression was initially increased from 1 hour after ischemic injury, followed by vascular endothelial growth factor expression. Hypoxia-inducible factor-1α immunoreactivity was detected in the ipsilateral cortical neurons of the infarct core and peri-infarct area. Vascular endothelial growth factor immunoreactivity was detected in bilateral cortex, but ipsilateral cortex staining intensity and numbers were greater than the contralateral cortex. Vascular endothelial growth factor immunoreactive cells were easily found along the peri-infarct area 12 hours after focal cerebral ischemia. The expression of nestin increased throughout the microvasculature in the ischemic core and the peri-infarct area in all experimental rats after 24 hours of ischemic injury. Nestin immunoreactivity increased in the subventricular zone during 12 hours to 3 days, and prominently increased in the ipsilateral cortex between 3–7 days. Nestin-labeled cells showed dual differentiation with microvessels near the infarct core and reactive astrocytes in the peri-infarct area. BrdU-labeled cells were increased gradually from day 1 in the ipsilateral subventricular zone and cortex, and numerous BrdU-labeled cells were observed in the peri-infarct area and non-lesioned cortex at 3 days. BrdU-labeled cells rather than neurons, were mainly co-labeled with nestin and GFAP. Early expressions of hypoxia-inducible factor-1α and vascular endothelial growth factor after ischemia made up the microenvironment to increase the neuronal plasticity of activated endogenous neural stem cells. Moreover, neural precursor cells after large-scale cortical injury could be recruited from the cortex nearby infarct core and subventricular zone.</P>

Effect of Basic Fibroblast Growth Factor on the Regeneration of the Allografted Sciatic Nerve in Rat

Choi, Moon-Gu,Kim, Hyoung Min,Lee, Da-Ro 가톨릭대학교 2000 Bulletin of The Catholic Research Institutes of Me Vol.28 No.-

Purpose : Recently peripheral nerve allograft was considered to be able to provide valuable nerve materials for large nerve defect. However, the rejection response and slow regeneration of graft have continued to be serious deterrent to application of nverve allograft. Although many studies for reducing graft immunogenicity have been reported, the method to promote nerve regeneration has not been reported. The purpose of this study is to investigate the promoting effects of the basic fibroblast growth factor(bFGF) on the regeneration of allografted nerve. Materials and Methods : Ninety-five female Wistar white rats and 90 allogenic Brown-Norway black rats were the recipients and the donors of 1.5 cm sciatic nerve graft mutually. Recipient rats were randomly allocated to cyclosporin A immunosuppressed group or control group. And each group was subdivided into non-bFGF subgroup, 10 pg-bFGF subgroup and 100 pg-bFGF subgroup. Regeneration of grafted nerves graft was assessed by histological and electomicroscopic studies at 4□, 8□ and 12□ weeks in non-CsA group. Results : Basic fibroblast growth factor showed its promoting effect on the regeneration of the allografted sciatic nerve at 4□ week in CsA-treated group and 8□ week in non-CsA group. Conclusion : Basic fibroblast growth factor promotes the regeneration of the allografted nerve in rat. (The Journal of Korean Orthopaedic Association 34(6):1019-1026, 1999)

Mouse Nerve Growth Factor Facilitates the Growth of Interspinal Schwannoma Cells by Activating NGF Receptors

Liu, Shu Yi,Liu, Sheng Ze,Li, Yu,Chen, Shi The Korean Neurosurgical Society 2019 Journal of Korean neurosurgical society Vol.62 No.6

Objective : Nerve growth factor (NGF) is a member of the neurotrophic factor family and plays a vital role in the physiological processes of organisms, especially in the nervous system. Many recent studies have reported that NGF is also involved in the regulation of tumourigenesis by either promoting or suppressing tumor growth, which depends on the location and type of tumor. However, little is known regarding the effect of NGF on interspinal schwannoma (IS). In the present study, we aimed to explored whether mouse nerve growth factor (mNGF), which is widely used in the clinic, can influence the growth of interspinal schwannoma cells (ISCs) isolated from IS in vitro. Methods : ISCs were isolated, cultured and identified by S-100 with immunofluorescence analysis. S-100-positive cells were divided into five groups, and separately cultured with various concentrations of mNGF (0 [phosphate buffered saline, PBS], 40, 80, 160, and 320 ng/mL) for 24 hours. Western blot and quantantive real time polymerase chain reaction (PCR) were applied to detect tyrosine kinase A (TrkA) receptor and p75 neurotrophin receptor ($p75^{NTR}$) in each group. Crystal violet staining was selected to assess the effect of mNGF (160 ng/mL) on ISCs growth. Results : ISCs growth was enhanced by mNGF in a dose-dependent manner. The result of crystal violet staining revealed that it was significantly strengthened the cells growth kinetics when cultured with 160 ng/mL mNGF compared to PBS group. Western blot and quantantive real time PCR discovered that TrkA receptor and mRNA expression were both up-regualated under the condition of mNGF, expecially in 160 ng/mL, while the exoression of $p75^{NTR}$ demonstrated no difference among groups. Conclusion : From these data, we conclude that exogenous mNGF can facilitate ISC growth by activating both TrkA receptor and $p75^{NTR}$. In addition, patients who are suffering from IS should not be administered mNGF in the clinic.

12주 복합운동이 비만 여고생의 뇌신경세포 생성인자 및 염증인자에 미치는 영향

서정표 ( Seo Jeongpyo ),허준회 ( Heo Junhoe ),김현준 ( Kim Hyunjun ),박장준 ( Park Jangjun ) 대한통합의학회 2020 대한통합의학회지 Vol.8 No.1

Purpose : To provide data on exercise prescription for obesity management and prevention of cardiovascular disease in girl’s high school and to prepare basic data for more effective exercise program for lifestyle improvement and prevention of lifestyle-related diseases. This study examines the effects on brain nerve growth factor and inflammatory factors, and the relationship between obesity factor and brain neuron cell production factor and inflammatory factor changes by complex exercise. Methods : The subjects of the study were obese students with a body fat percentage of 30 % or higher after obtaining body fat percentage of high school girls in C-city. Among them, 20 students who wanted to participate in the program of this study and did not participate in special exercise and diet therapy within the last 6 months were radio-sampled into groups of exercise group and control group, but attendance rate was low and The final exercise group (9) and control group (9) were measured, except for one student who did not respond. Results : Analysis of the range of variation in body composition, BMI, lean body mass, and the interaction between the groups showed significant differences (p<.05). TC, TG, HDL-C, and LDL-C as variables of blood lipids, TC and TG were not significantly different and TG was significantly different (p<.05) in interactions. HDL-C showed a significant difference (p<.01) in interactions, an increase in exercise group, and a significant decrease in control group (p<.05). There was a significant difference (p<.05) in BDNF interaction, an increase in the exercise group and a decrease in the control group, but no significant difference. NGF tended to increase in both exercise and control groups. IL-6 had a significant difference in timing (p<.05) and significantly decreased (p<.01) in the exercise group, and TNF-α interacted with timing (p<.05), and a significant increase in the control group. Conclusion : This study confirmed 12-week compound exercise program was effective in increasing the expression of basal fitness or CNS factor, but not enough to actually improve brain function. Fat mass and obesity are also affecting vascular inflammatory factors.

폴리아민이 흰쥐 복재신경 재생에 미치는 영향 - Ⅰ. 수초신경섬유의 직경과 수초 두께의 변화

이종은,문혜원,이원택,박경아 대한해부학회 1994 Anatomy & Cell Biology Vol.27 No.3

Effects of Barefoot Walking Exercise on Female Hormone, Brain Nerve Growth Factors and Immunoglobulins in Postmenopausal Women

호은석(Eun-Seok Ho),안민지(Min-Ji An)김경래(Kyeong-Lae Kim) 한국교원대학교 뇌기반교육연구소 2021 Brain, Digital, & Learning Vol.11 No.4

This study investigate the effects of a 12-week barefoot walking exercise on female hormone, brain nerve growth factors and immunoglobulins in postmenopausal women. It aimed to provide the fundamental data for developing an effective exercise program to help postmenopausal women maintain a physically, psychologically, and socially healthy life in senescence. Postmenopausal women in C-city, Chungcheongbuk-do, were recruited and randomized between the barefoot walking group(n=11) and the shoes walking group(n=11) for subsequent analyses. The walking exercise program consisted of three 60-minute sessions per week for 12 weeks. The levels of estrogen, brain nerve growth factors and immunoglobulins were measured before and after the exercise. Two-way repeated measure ANOVA was performed to analyze the before-after difference between the barefoot walking group and the shoes walking group. The results acquired from this study are as follows. First, the estrogen levels during the 12-week walking exercise intervention were not influenced by the group or duration. However, the duration of the exercise significantly affected the barefoot walking group. Second, the brain nerve growth factors, namely, brain-derived neurotrophic factor(BDNF), insulin-like growth factor-I(IGF-I) and vascular endothelial growth factor(VEGF) were not significantly influenced by the group or duration during the 12-week exercise intervention. However, the barefoot and shoes groups significantly affected BDNF and VEGF. The duration of the exercise did not affect IGF-I in both groups. Third, IgG was significantly influenced by the group and duration during the 12-week exercise intervention. However, IgA and IgM were not significantly affected by the exercise group or duration. Exercise duration significantly affected the IgG of the shoes walking group and IgM of the barefoot walking group.

Regenerative Effect of the Polydeoxyribonucleotide after Sciatic Nerve Transection in Mouse

박지원,김민수,김석권,이근철,이진화 한국조직공학과 재생의학회 2015 조직공학과 재생의학 Vol.12 No.6

Factors that have effects on postoperative nerve regeneration are surgery period, maneuver and the use of material that promotes nerve regeneration. Of various materials that promote nerve regeneration, vascular endothelial growth factor (VEGF) is known as cytokine that plays an important role in regenerating not only vessels but also nerves. Polydeoxyribonucleotide (PDRN) promotes the synthesis of VEGF. Thus, assuming that PDRN has the effect of peripheral nerve regeneration, mice were classified into a group with PDRN being administered, a group with VEGF being administered, and a group with nothing administered. Placentex® (PDRN) and VEGF were used, and 40 male mice were used. Then, the mice were classified into two test groups with Placentex® and VEGF injection, and the control group with NaCl 0.9%. After 2 and 4 weeks, the mice were killed and their histological examination was conducted through electron microscope. It revealed that each group was insignificantly different in terms of all comparative items, but the finding after 4 weeks revealed that the test group with PDRN and VEGF showed a statistically significant effect of promoting nerve regeneration. Further, all histological examinations found that the group with PDRN and VEGF promoted nerve regeneration. Regarding the period, the group with VEGF, compared to the PDRN group, showed a better result, but the difference proved to be statistically insignificant. It was confirmed that PDRN had the effect of promoting nerve regeneration; thus PDRN can help restore peripheral nerve damage, caused by trauma and surgery, and promote the prognosis.