• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.4
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• pp.896-902
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• 2008

Yukmijihwang-tang(YM) is used in Oriental medicine for treatments of diverse systemic symptoms including neurological dosorders. The present study was performed to examine potential effects of YM on growth-promoting activity of injured sciatic nerve axons. YM treatment in the injured sciatic nerve induced enhanced distal elongation of injured axons when measured 3 and 7 days after injury. Retrograde tracing of sciatic nerve axons showed YM-mediated increases in the number of DiI-labeled dorsal root ganglion (DRG) sensory neurons and spinal cord motor neurons at 3 days after injury. Hoechst nuclear staining showed that non-neuronal cell population was largely elevated by YM treatment in distal nerve area undergoing axonal regeneration. Furthermore, phospho-Erk1/2 protein levels were upregulated by YM treatment in the injured nerve area. These data suggest that YM may play a role in facilitated axonal regeneration in injured peripheral nerves. Further investigations of individual herbal components would be useful to explore effective molecular components and develop therapeutic strategies.

• Journal of Korean Neurosurgical Society
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• v.52 no.4
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• pp.377-383
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• 2012

Objective : Detection of focal non-hemorrhagic lesion (NHL) has become more efficient in diffuse axonal injury (DAI) patients using an MRI. The aims of this study are to find out the radiological distribution, progress of NHL and its clinical significance. Methods : Between September 2005 and October 2011, 32 individuals with NHLs on brain MRI were enrolled. NHLs were classified by brain location into 4 major districts and 13 detailed locations including cortical and subcortical, corpus callosum, deep nuclei and adjacent area, and brainstem. The severity of NHL was scored from grades 1 to 4, according to the number of districts involved. Fourteen patients with NHL were available for MRI follow-up and an investigation of the changes was conducted. Results : Thirty-two patients had 59 NHLs. The most common district of NHL was cortical and subcortical area; 15 patients had 20 NHSs. However the most common specific location was the splenium of the corpus callosum; 14 patients had 14 lesions. The more lesions patients had, the lower the GCS, however, this was not a statistically meaningful difference. On follow-up MRI in 14 patients, out of 24 lesions, 13 NHLs resolved, 5 showed cystic change, and 6 showed atrophic changes. Conclusion : NHLs were located most commonly in the splenium and occur frequently in the thalamus and the mesial temporal lobe. Because most NHS occur concomitantly with hemorrhagic lesions, it was difficult to determine their effects on prognosis. Since most NHLs resolve completely, they are probably less significant to prognosis than hemorrhagic lesions.

• Proceedings of the Korean Society of Medical Physics Conference
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• 2005.04a
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• pp.32-34
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• 2005

Purpose: To investigate the metabolic changes in the motor and motor association cortices following axonal injury in the internal capsule that was caused by deep intracerebral hematoma. Materials and Methods: Using proton magnetic resonance spectroscopy (1H MRS), the authors studied the primary motor cortices (M-1) and supplementary motor areas (SMA) of 9 hemiparetic patients with documentable hemiparesis of varying severity, and we studied 10 normal volunteers as controls. To measure the M-1 and SMA biochemical changes, 4 separate single volumes of interest (VOIs) were located bilaterally in the affected and unaffected hemisphere (AH and UH). Results: 1H MRS provided a neuronal and axonal viability index by measuring levels of N-acetylaspartate (NAA) and creatine/phosphocreatine (Cr). The M-1/SMA NAA/Cr ratios of the AH and UH in patients, and the AH and normal volunteers were compared. The NAA/Cr ratios of the M-1 and SMA in AH, and the SMA in UH were significantly lower than those of normal volunteers. Conclusion: These 1H MRS findings indicate that axonal injury in the descending motor pathway at the level of internal capsule could induce metabolic changes in the higher centers of the motor pathway.

• Journal of Acupuncture Research
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• v.29 no.6
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• pp.23-34
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• 2012

Objectives : This study was performed to define clinical character of peripheral facial nerve injury. Methods : 36 patients was identified with peripheral facial nerve injury among 1128 patients who visited the Facial Palsy Center in Kyung Hee University Hospital at Gang-dong between January 2010 and November 2011. We reviewed the medical records including gender, age, cause, symptom, period of treatment, and axonal loss. Results : Most common cause of peripheral facial nerve injury was iatrogenic surgery, followed by direct trauma, neoplastic disorders. Patients with facial nerve injury commonly complain about facial palsy(ipsilateal or bilateral), followed by paresthesia, facial spasm, facial pain, auricular pain. Peripheral facial nerve injury group showed worse electrophysiological pattern and younger onset age compared with Bell's palsy group. Conclusion : This study was designed for 36 patients and further studies are necessary.

• 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.

• The Journal of Korean Physical Therapy
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• v.15 no.2
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• pp.67-74
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• 2003

Nervous system is clinically important, and involved in most disorders directly or indirectly. It could be injury and be a source of symptoms. Injury of central or peripheral nervous system injury may affect that mechanism and interrupt normal function. An understanding of the concepts of axonal transport is important for physical therapist who treat injury of nerves. Three connective tissue layers are the endoneurium, perineurium, epineurium. Each has its own special structural characteristics and functional properties. The blood supply to the nervous system is well equipped in all dynamic and static postures with intrinsic and extrinsic vasculation. After nerve injury, alternations in the ionic compression or pressures within this environment may interfere with blood flow and, consequently conduction and the flow of axoplasm. The cytoskeleton are not static. On the contrary, elements of the cytoskeleton are dynamically regulated and are very likely in continual motion. It permits neural mobility. There are different axonal transport systems within a single axon, of which two main flows have been identified : First, anterograde transport system, Secondly, retrograde transport system. The nervous system adapts lengthening in two basic ways. The one is that the development of tension or increased pressure within the tissues, increased intradural pressure. The other is movements that are gross movement and movement occurring intraneurally between the connective tissues and the neural tissues. In this article, we emphasize the biologic aspects of nervous system that influenced by therapeutic approaches. Although identified scientific information in basic science is utilized at clinic, we would attain the more therapeutic effects and develop the physical therapy science.

• 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 Haehwa Medicine
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• v.29 no.1
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• pp.18-25
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• 2020

Objective: The goal of this study is to investigate whether peripheral axonal regeneration is affected by diabetes in experimental animals. Method: Sprague Dawely rat was injected with 45~50 mg/kg of streptozotocin (STZ) to generate an animal model of diabetes. Three months after STZ injection, sciatic nerve (2 cm length) was removed and the same length of nerve segments from STZ-injected animal or from control animal (CTL) was transplanted into STZ-injected animals (STZ-STZ and STZ-CTL respectively). Similarly, sciatic nerve segments from STZ-injected animal or from control animal were grafted into the control animals (CTL-STZ and CTL-CTL respectively). All animals were sacrificed 2 weeks after transplantation. Sciatic nerve sections were prepared and subjected to immunofluorescence staining analysis. Results: Immunofluorescence staining for NF-200 showed that distal elongation of regenerating axons reached 40~80% of proximal neve in both CTL-STZ and CTL-CTL groups. However, distal elongation in both STZ-STZ and STZ-CTL groups were 20~60% of proximal nerve. Furthermore, measurement of axonal regeneration after immuno-staining with SCG10 showed that the scores of distal elongation relative to proximal nerve were 50~90% in CTL-CTL and CTL-STZ groups and 10-60% in STZ-CTL and STZ-STZ. Conclusions: Our data showed that the levels of axonal regeneration were not affected irrespective of whether they were from STZ- or CTL graft, but were greatly reduced when the nerves were transplanted into the STZ host.

• 대한핵의학회:학술대회논문집
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• 1996.05a
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• pp.181-181
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• 1996

• Molecules and Cells
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• v.37 no.8
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• pp.613-619
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• 2014

The optic nerve often suffers regenerative failure after injury, leading to serious visual impairment such as glaucoma. The main inhibitory factors, including Nogo-A, oligodendrocyte myelin glycoprotein, and myelin-associated glycoprotein, exert their inhibitory effects on axonal growth through the same receptor, the Nogo-66 receptor (NgR). Oncomodulin (OM), a calcium-binding protein with a molecular weight of an ~12 kDa, which is secreted from activated macrophages, has been demonstrated to have high and specific affinity for retinal ganglion cells (RGC) and promote greater axonal regeneration than other known polypeptide growth factors. Protamine has been reported to effectively deliver small interference RNA (siRNA) into cells. Accordingly, a fusion protein of OM and truncated protamine (tp) may be used as a vehicle for the delivery of NgR siRNA into RGC for gene therapy. To test this hypothesis, we constructed OM and tp fusion protein (OM/tp) expression vectors. Using the indirect immunofluorescence labeling method, OM/tp fusion proteins were found to have a high affinity for RGC. The gel shift assay showed that the OM/tp fusion proteins retained the capacity to bind to DNA. Using OM/tp fusion proteins as a delivery tool, the siRNA of NgR was effectively transfected into cells and significantly down-regulated NgR expression levels. More importantly, OM/tp-NgR siRNA dramatically promoted axonal growth of RGC compared with the application of OM/tp recombinant protein or NgR siRNA alone in vitro. In addition, OM/tp-NgR siRNA highly elevated intracellular cyclic adenosine monophosphate (cAMP) levels and inhibited activation of the Ras homolog gene family, member A (RhoA). Taken together, our data demonstrated that the recombinant OM/tp fusion proteins retained the functions of both OM and tp, and that OM/tp-NgR siRNA might potentially be used for the treatment of optic nerve injury.