• Journal of Korean Medicine Rehabilitation
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• v.18 no.4
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• pp.39-61
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• 2008

Objectives : The present study was performed to investigate whether acupuncture stimulation in the rats affected regeneration properties of the injured sciatic nerve. A differential effect of acupuncture stimulation on the one point near the spinal nerve root controlling sciatic nerve activity and the other point in the peripheral area subordinated by injured nerve was compared. Materials and Methods: Rat sciatic nerves were injured by crush, and the effects on axonal regeneration on injured sciatic nerves were evaluated by acupuncture stimulation at two different regions. In proximal acupuncture stimulation group, acupuncture stimulation was performed on Huatuo Jiaji(EX B2) points located from L5 to S1 vertebral levels to stimulate the nearest spinal nerve root that innervates sciatic nerves. In distal acupuncture stimulation group, acupuncture stimulation was performed on Zusanli(ST 36) and Weizhong(BL 40) points to stimulate at peripheral area dominated by injured sciatic nerves. Acupuncture stimulation was given every other days for 1 or 2 weeks. Sciatic nerve tissues collected from acupuncture stimulation experimental groups, injury control group, and intact animal group were used for protein analysis by Western blotting or Hoechst nuclear staining. To determine axonal regeneration, Dil fluorescence dye was injected into the sciatic nerve 0.5 cm distal to the injury site in individual animal groups and Dil-labeled cells by retrograde tracing were measured in the DRG at lumbar 5 or in the spinal cord. DRG sensory neurons prepared from individual animal groups were used to measure the extent of neurite outgrowth and for immunofluorescence staining with anti-GAP-43 antibody. Results : Animal groups given proximal or distal acupuncture stimulation showed upregulation of GAP-43 and Cdc2 protein levels in the sciatic nerve at 7 days after injury. Cdk2 protein levels were strongly induced by nerve injury, but did not show changes by acupuncture stimulation. Phospho-Erk1/2 protein levels were elevated by acupuncture stimulation above those present in the injury control animals. These increase in regeneration-associated protein levels appeared to be related with increase cell proliferation in the injured sciatic nerves. Hoechst 33258 staining of sciatic nerve tissue to visualize nuclei of individual cells showed increased Schwann cell number in the distal portion of the injured nerve 7 and 14 days after injury and further increases by acupuncture stimulation particularly at the proximal position. Measurement of axonal regeneration by retrograde tracing showed significantly increased Dil-labeled cells in proximal acupuncture stimulation group compared to distal acupuncture stimulation group and injury control group. Finally, an evaluation of axonal regeneration by retrograde tracing showed increased number of Dil labeled cells in the DRG at lumbar 5 or in the ventral horn of the spinal cord at lower thoracic level at 7 days after nerve injury. Conclusions : The present data show that the proximal acupuncture stimulation at Huatuo Jiaji(EX B2) points governing injured sciatic nerves was more effective for axonal regeneration than the distal acupuncture stimulation. Further studies on functional recovery or associated molecular mechanisms should be critical for developing animal models and clinical applications.

• Journal of Korean Medicine Rehabilitation
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• v.19 no.2
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• pp.51-72
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• 2009

Objectives : This study was designed to evaluate the effects of Ohyaksungi-san(Wuyaoshungi-san) and Jungsongouhyul pharmacopuncture on pain reduction and nerve regeneration after crush injury in rat sciatic nerve. Methods : Animal model was produced through crush injury of right sciatic nerve and they were divided into four groups; Group I: no treatment control group; Group II: experimental group treated with Ohyaksungi-san(Wuyaoshungi-san); Group III: experimental group treated with Jungsongouhyul pharmacopuncture; Group IV: experimental group treated with Ohyaksungi-san(Wuyaoshungi-san) and Jungsongouhyul pharmacopuncture. For the assessment of pain, this study was observed the paw withdrawal latency(PWL) and immunoreactivity on the substance-P. For the assessment of nerve regeneration, the sciatic functional index(SFI) and immunoreactivity on the BDNF were measured. Results : 1. In the assessment of pain, the PWL of experimental groups was significantly higher than control group and group IV was significantly higher than other groups at the all days. 2. In immunohistochemical response of substance-P, as time passes, the immunoreactivity of all groups were decreased gradully. Especially, group IV had the lowest immunoreactivity. 3. In the assessment of SFI, the SFI of experimental groups were significantly higher than control group. 4. In immunohistochemical response of BDNF, the BDNF immunoreactivity of all groups was significantly higher than control group and especially, group IV had the highest immunoreactivity at the 14 days after injury. 5. H & E stain was used on the liver and kidney to investigate toxic effect of Jungsongouhyul pharmacopuncture and Ohyaksungi-san(Wuyaoshungi-san) on on 21 days after injury. However there were no any toxic effects both control group and experimental groups. Conclusions : On the basis of these results, we propose that Ohyaksungi-san(Wuyaoshungi-san) and Jungsongouhyul pharmacopuncture were related to pain reduction and motor nerve recovery, also decreased substance-P expression and increased BDNF expression after crush injury of sciatic nerve, especially these two treatments could be more effective when they were combined simultaneously.

• Journal of Korean Medicine Rehabilitation
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• v.18 no.2
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• pp.61-79
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• 2008

Objectives : The purpose of this study was to identify the effect of Dokwal-tang(Duhuo-tang) and Jungsongouhyul Pharmacopuncture on pain control and nerve regeneration after crush injury in rat sciatic nerve. Methods : Animal model was produced through right sciatic nerve crush injury and they were randomly divided into four groups; Group I: no treatment control group; Group II: experimental group treated with Dokwal-tang(Duhuo-tang); Group III: experimental group treated with Jungsongouhyul Pharmacopuncture; Group IV: experimental group treated with Dokwal-tang(Duhuo-tang) and Jungsongouhyul Pharmacopuncture. For the pain assessment, this study was observed the paw withdrawal latency(PWL) and immunoreactivity on the substance-P. For the nerve regeneration assessment, the sciatic functional index(SFI) and immunoreactivity on the GAP-43 were measured. Results : 1. In the pain assessment, the PWL of experimental groups were significantly higher than control group and group IV was significantly higher than other groups. 2. In immunohistochemical response of substance-P, as time passes, all groups had decreased immunoreactivity gradually. Specially, group IV was observed the lowest immunoreactivity. 3. In the assessment of SFI, the SFI of experimental groups were significantly higher than control group. 4. In immunohistochemical response of GAP-43, all groups had higher GAP-43 immunoreactivity at the 14 days from post-injury and at the all days, control group was observed most lower immunoreactivity and group IV was observed most higher immunoreactivity. Conclusions : These results of this study suggest that Dokwal-tang(Duhuo-tang) and Jungsongouhyul Pharmacopuncture was related with pain inhibition and motor nerve recovery, and decreased substance-P expression and increased GAP-43 expression after sciatic nerve crush injury.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.3
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• pp.270-278
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• 2000

This study was conducted to compare the vein graft with the nerve graft, and evaluated the availability of the vein graft on the reconstruction of the inferior alveolar nerve defect. The experimental animals were 12 rabbits weighing $1.5{\sim}2.0kg$, divided into 3 groups : sham operation group, vein conduit group and nerve graft group. All nerves were excised and histomorphometric analysis was performed at 2, 4, 6, 12, 16 weeks after operation. The obtained results were as follows. 1. Histologic examination revealed the regenerated nerve fibers within the lumen of the vein graft and nerve graft at 6 weeks after repair. 2. Axon diameter was significantly larger in nerve graft group(p<0.05) than in vein graft group at 6weeks, and larger in nerve graft group than in vein graft group at 16weeks. 3. Axon density was higher in the vein graft group at 16 weeks. 4. The myelin of the regenerated nerve fibers in distal segment of the vein graft group was thick, approaching the proximal segment at 16weeks. This means remyelination in distal segment in the vein graft group. These results suggested that autogenous vein graft may be used as an alternative to autogenous nerve graft.

• Archives of Plastic Surgery
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• v.39 no.1
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• pp.71-75
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• 2012

Recurrent laryngeal nerve paralysis is the most common and serious complication after thyroid cancer surgery. The objective of this study was to report the advantages of the vein wrapping technique for nerve reconstruction in patients with thyroid cancer invading the recurrent laryngeal nerve and its effects on postoperative phonatory function. The subjects were three patients who underwent resection of the recurrent laryngeal nerve during surgical extirpation of papillary thyroid cancer. Free ansa cervicalis nerve graft or direct neurorrhaphy with a vein wrapping technique was used to facilitate nerve regeneration, protect the anastomosed nerve site mechanically, and prevent neuroma formation. One-year postoperative laryngoscopic examination revealed good vocal cord mobility. Maximum phonation time ($19.5{\pm}0.3$ sec) was longer than a previously-reported value in conventional reconstruction patients ($18.8{\pm}6.6$ sec). The present phonation efficiency index ($7.88{\pm}0.78$) was higher than that previously calculated in conventional reconstruction ($7.59{\pm}2.82$). The mean value of the Voice Handicap Index-10 was 6, which was within the normal range. This study demonstrates improvement in phonation indices measured 1 year after recurrent laryngeal nerve reconstruction. Our results confirm that the vein wrapping technique has theoretical advantages and could be favored over conventional reconstruction techniques for invenerate nerve injuries.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.6
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• pp.1666-1672
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• 2005

Oriental medicinal drugs have a broad spectrum of clinical use for the cure of nervous system diseases including brain ischemic damages or neuropathies. Yet, specific drugs or drug components used in the oriental medicine in relation to none fiber regeneration are not known. In the present study, possible growth promoting effects of oriental medicinal drugs were investigated in the injured sciatic nerve system in the rat. By immunofluorescence staining, we found that Jahageo (JHG, Hominis placenta) increased Induction levels of axonal growth associated protein GAP-43 in the rat sciatic none. Small growth promoting activity was found in Golsebo (GSB, Drynariae rhizoma) and Baikhasuo (BHSO, Polygoni multiflori radix) drugs. JHG also increased cell cycle protein Cdc2 levels in the injured area of the sciatic nerves. Immunofluorescence staining indicated that induced Cdc2 protein was mostly localized in the Schwann cells in the injury area, implying that JHG activity might be related to increased Schwann cell proliferation during axonal regeneration. Moreover, levels of phospho-extracellular signal-regulated (ERK) pathway in the injured neNes were elevated by JHG treatment while levels of total ERK were unaltered. In vivo measurement of axonal regeneration using retrograde tracer showed that JHG, GSB and BHSO significantly enhanced Dil-labeled regenerating motor neurons compared with saline control. The present data suggest that oriental medicinal drugs such as JHG, GSB, and BHSO may be a useful target for developing specific drugs of axonal regeneration.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.45 no.5
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• pp.233-240
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• 2019

Trigeminal nerve injury as a consequence of lower third molar surgery is a notorious complication and may affect the patient in long term. Inferior alveolar nerve (IAN) and lingual nerve (LN) injury result in different degree of neurosensory deficit and also other neurological symptoms. The long term effects may include persistent sensory loss, chronic pain and depression. It is crucial to understand the pathophysiology of the nerve injury from lower third molar surgery. Surgery remains the most promising treatment in moderate-to-severe nerve injuries. There are limitations in the current treatment methods and full recovery is not commonly achievable. It is better to prevent nerve injury than to treat with unpredictable results. Coronectomy has been proved to be effective in reducing IAN injury and carries minimal long-term morbidity. New technologies, like the roles of erythropoietin and stem cell therapy, are being investigated for neuroprotection and neural regeneration. Breakthroughs in basic and translational research are required to improve the clinical outcomes of the current treatment modalities of third molar surgery-related nerve injury.

• Journal of Veterinary Clinics
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• v.19 no.3
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• pp.316-321
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• 2002

The purpose of this study was to examine the effect of Ga-As(Gallium-Arsenide, wave length; 904 nm) infrared laser irradiation on healing of the experimentally crush injured rat sciatic nerves. The bilateral sciatic nerves of 43 adult male Sprague-Dawley rats were compressed surgically with a straight hemostat (1 mm width). The right legs of all the rats were irradiated using a 27 mW Ga-As infrared laser (laser irradiated group). The radiation procedure was administered for 3 minutes every day for 1, 3, 5, and 7 weeks in each group. Left legs were not irradiated and served as the control group. The numbers of total myelinated axon and degenerated myelin in the sciatic nerves of bilateral legs were measured and analyzed with mage analysis system in order to make a morphological analysis of the effect of the Ga-As infrared laser on injured nerves. Total number of myelinated axons was increased with time interval, especially in the 1, 3. and 5 week of irradiated group. Conversely, the number of degenerated myelin was decreased with time interval, especially in the irradiated group. The effects in the irradiated group were more pronounced than those of the control group. In conclusion, the Ga-As infrared laser irradiation is a useful adjuvant therapy to the regeneration of the peripheral nerve injury.

• Journal of Haehwa Medicine
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• v.14 no.1
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• pp.201-211
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• 2005

Cdc2 kinase is a prototypical cyclin-dependent kinase critical for G2 to M phase cell cycle transition. Yet, its function in the nervous system is largely unknown. Here, we investigated possible role of Cdc2 in axonal regeneration using sciatic nerve system in rat. Cdc2 protein levels and activity were increased in the injured sciatic nerves 3 and 7 days after crush injury and then decreased to basal level 14 days later. Administration of Cdc2 kinase inhibitor roscovitine in vivo at the time of crush injury significantly inhibited axonal regeneration when regrowing axons were analyzed using retrograde tracers. Cdc2 protein levels in cultured Schwann cells which were prepared from sciatic nerves 7 days after crush injury were much higher compared with those from uninjured sciatic nerves, suggesting that Cdc2 protein expression was primarily induced in the Schwann cells. To further investigate Cdc2 function in Schwann cell, we examined changes in cultured Schwann cell proliferation and migration in culture system. Both the number of proliferating Schwann cells and the extent of neurite outgrowth from co-cultured DRG neurons were significantly decreased by Cdc2 inhibitor roscovitine treatment in DRG culture which was prepared from animals with sciatic nerve injury for 7 days. Also, Schwann cell migration in the injured sciatic nerve explant was significantly inhibited by roscovitine treatment. Taken together, the present data suggest that Cdc2 may be involved in peripheral nerve regeneration via Schwann cell proliferation and migration.

• The Journal of Korean Medicine
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• v.29 no.5
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• pp.14-28
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• 2008

Objective : This study was carried out to understand effects of ginseng(hearinafter ; GS, Panax Ginseng) extract on regeneration responses on injured sciatic nerves in rats. Methods :Using white mouse, we damaged sciatic nerve & central nerve, and then applied GS to the lesion. Then we observed regeneration of axon and non-neuron. Results : 1. NF-200 protein immunostaining for the visualization of axons showed more distal elongation of sciatic nerve axons in GS-treated group than saline-treated control 3 and 7 days after crush injury. 2. GAP-43 protein was increased in the injured sciatic nerve and further increased by GS treatment. Enhanced GAP-43 protein signals were also observed in DRG prepared from the rats given nerve injury and GS treatment. 3. GS treatment in vivo induced enhanced neurite outgrowth in preconditioned DRG sensory neurons. In vitro treatment of GS on sensory neurons from intact DRG also caused increased neurite outgrowth. 4. Phospho-Erk1/2 protein levels were higher in the injured nerve treated with GS than saline. Phospho-Erk1/2 protein signals were mostly found in the axons in the injured nerve. 5. NGF and Cdc2 protein levels showed slight increases in the injured nerves of GS-treated group compared to saline-treated group. 6. The number of Schwann cell population was significantly increased by GS treatment in the injured sciatic nerve. GS treatment with cultured Schwann cells increased proliferation and Cdc2 protein signals. 7. GS pretreatment into the injured spinal cord generated increased astrocyte proliferation and oligodendrocytes in culture. In vitro treatment of GS resulted in more differentiated pericytoplasmic processes compared with saline treatment. 8. More arborization around the injury cavity and the occurrence at the caudal region of CST axons were observed in GS-treated group than in saline-treated group. Conclusion :GS extract may have the growth-promoting activity on regenerating axons in both peripheral and central nervous systems.