• 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.

• Journal of Oral Medicine and Pain
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• v.41 no.4
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• pp.145-154
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• 2016

Transcutaneous electrical nerve stimulation (TENS) is one of the representative physiotherapical modalities used for the treatment of various musculoskeletal disorders by the application of electrical stimuli. In dental practice, it has long been used in the treatment of acute and chronic orofacial pain conditions including temporomandibular disorders. TENS is the delivery of therapeutic electrical stimuli with a variety of electrical intensity, frequency and duration to stimulate peripheral nerve through surface electrodes with various form and placement. While controversy still remains over the clinical effectiveness and application of TENS, basic understanding of its electrical properties and the expected biological reactions is important to increase the therapeutic effect and decrease the risk of possible side effects. This review, therefore, focuses on basic understanding of TENS including its underlying mechanisms and stimulation parameters.

• The Journal of Korean Physical Therapy
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• v.12 no.3
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• pp.395-406
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• 2000

In general. it is known that central nervous system associated with nerve injury and regeneration in mature cann't regenerate, unlikely peripheral nervous system, due to various reasons. Although a lot of Patients arc suffered with central nervous system injury in the world, but there art a few resolution and researches and investigations. 'rho effect of central nervous system regeneration was partly revealed by many researchers. In this article, we describe about recovery (inclusive of axonal regeneration, remyelination, repair of spinal cord) and associated factors(inclusive of macrophage and autoimmune T-cell. neural stem cells. Nogo) after central nervous system injury.

• 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 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.

• 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.

• The Journal of Korean Medicine
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• v.30 no.3
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• pp.39-50
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• 2009

Objective : The aim of this study was to evaluate the effects of Aconiti ciliare tuber on the descending pain and the recovery of locomotor function that results from sciatic crushed nerve injury in rats. Method : In order to assess the effects of the aqueous extract of Aconiti ciliare tuber on the recovery rate of locomotor function, we investigated the walking track analysis, and for the effects on the pain control we investigated brain-derived neurotrophic factor (BDNF) and inducible nitric oxide synthase (iNOS) expression in the sciatic nerve and on the expressions of c-Fos in the ventrolateral periaqueductal gray (vlPAG) region resulting from the sciatic crushed nerve injury in rats. Result : Treatment with Aconiti ciliare tuber significantly enhanced the SFIvalue, enhanced BDNF expression, decreased iNOS expression, and suppressed c-Fos expression. The present results showed that Aconiti ciliare tuber facilitated functional recovery following sciatic crushed nerve injury in rats. The recovery mechanisms of SFI by Aconiti ciliare tuber might be ascribed to the increase of BDNF expression for nerve regeneration and reinnervation and to the suppression of iNOS expression for inhibiting nerve inflammation. Conclusion : In this process it has been shown that Aconiti ciliare tuber can be used for pain control and functional recovery from peripheral nerve injury.

• Journal of The Korean Dental Society of Anesthesiology
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• v.14 no.2
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• pp.89-94
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• 2014

Local anesthesia known as the safe and essential procedure to control pain in dentistry may cause sensory changes such as paresthesia or altered taste at the affected sites after even successful local anesthesia. Although the prognosis of the nerve injuries after local anesthesia is favorable, it might cause prolonged problems such as dysesthesia. The lingual nerve is a single fascicle at the level of the lingual among 1/3 of patients and more movable during regeneration compared to the inferior alveolar nerve after the injury. As a result, the lingual nerve is more vulnerable and has poorer outcomes. More vigilant clinical considerations are required to the lingual nerve injury after local anesthesia. Generally, more than 80% of cases are spontaneously resolved within 2 weeks after the local anesthesia even without any specific treatment. However, the patient having long lasting abnormal sensations more than 2 weeks needs specialists' care for further assessment. In case of dysesthesia which is a symptom of neuropathic pain, immediate referral to specialists is mandatory. The exact mechanism, how to prevent its occurrence, or specific treatments of the nerve injury related to the local anesthesia have not been elucidated. To prepare clinical or medicolegal problems, many cautious considerations are given to the patients who complain sensory changes after local anesthesia.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.17 no.1
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• pp.96-107
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• 1995

The purpose of this experimental study was to examine and compare the regeneration capacity between crushed nerve & transected nerve. For this study, 20 Sprague-Dawley female albino rats were used as experimental animals and divided into two groups. In group 1, the sciatic nerves were crushed 6mm. in length for 1 min. using maximum force with a needle holder. In group 2, the sciatic nerves were resected 6mm. in length and the gaps were encased by inserting the proximal and distal stumps into each end of silicone tubes. The animals were sacrificed 1 month & 2 months after the experiment. All specimens were fixed in 2.5% glutaraldehyde and 1% Osmium tetroxide solution then embedded in epon 812 and were cross-sectioned at $1{\mu}m.$ After these procedures, specimens were observed under Light microscope. The results obtained were as follows. 1. Group 1 showed greter diameters of regenerating nerves than group 2. 2. Group 1 showed greater number of axons than group 2.

• International Journal of Oral Biology
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• v.31 no.3
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• pp.87-92
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• 2006

Schwann cells play an important role in peripheral nerve regeneration. Upon nerve injury, Schwann cells are activated and produce various proinflammatory mediators including IL-6, LIF and MCP-1, which result in the recruitment of macrophages and phagocytosis of myelin debris. However, it is unclear how the nerve injury induces Schwann cell activation. Recently, it was reported that necrotic cells induce immune cell activation via toll-like receptors (TLRs). This suggests that the TLRs expressed on Schwann cells may recognize nerve damage by binding to the endogenous ligands secreted by the damaged nerve, thereby inducing Schwann cell activation. To explore the possibility, we stimulated iSC, a rat Schwann cell line, with damaged neuronal cell extracts (DNCE). The stimulation of iSC with DNCE induced the expression of various inflammatory mediators including IL-6, LIF, MCP-1 and iNOS. Studies on the signaling pathway indicate that $NF-{\kappa}B$, p38 and JNK activation are required for the DNCE-induced inflammatory gene expression. Furthermore, treatment of either anti-TLR3 neutralizing antibody or ribonuclease inhibited the DNCE-induced proinflammatory gene expression in iSC. In summary, these results suggest that damaged neuronal cells induce inflammatory Schwann cell activation via TLR3, which might be involved in the Wallerian degeneration after a peripheral nerve injury.