• Molecules and Cells
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• v.38 no.11
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• pp.1013-1021
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• 2015

Most of the axons in the vertebrate nervous system are surrounded by a lipid-rich membrane called myelin, which promotes rapid conduction of nerve impulses and protects the axon from being damaged. Multiple sclerosis (MS) is a chronic demyelinating disease of the CNS characterized by infiltration of immune cells and progressive damage to myelin and axons. One potential way to treat MS is to enhance the endogenous remyelination process, but at present there are no available treatments to promote remyelination in patients with demyelinating diseases. Sulfasalazine is an anti-inflammatory and immune-modulating drug that is used in rheumatology and inflammatory bowel disease. Its anti-inflammatory and immunomodulatory properties prompted us to test the ability of sulfasalazine to promote remyelination. In this study, we found that sulfasalazine promotes remyelination in the CNS of a transgenic zebrafish model of NTR/MTZ-induced demyelination. We also found that sulfasalazine treatment reduced the number of macrophages/microglia in the CNS of demyelinated zebrafish larvae, suggesting that the acceleration of remyelination is mediated by the immunomodulatory function of sulfasalazine. Our data suggest that temporal modulation of the immune response by sulfasalazine can be used to overcome MS by enhancing myelin repair and remyelination in the CNS.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.319-328
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• 2023

Background: Demyelination has been observed in neurological disorders, motivating researchers to search for components for enhancing remyelination. Previously we found that Rb1, a major ginsenoside in Korean Red Ginseng (KRG), enhances myelin formation. However, it has not been studied whether Rb1 or KRG function in remyelination after demyelination in vivo. Methods: Mice were fed 0.2% cuprizone-containing chow for 5 weeks and returned to normal chow with daily oral injection of vehicle, KRG, or Rb1 for 3 weeks. Brain sections were stained with luxol fast blue (LFB) staining or immunohistochemistry. Primary oligodendrocyte or astrocyte cultures were subject to normal or stress condition with KRG or Rb1 treatment to measure gene expressions of myelin, endoplasmic reticulum (ER) stress, antioxidants and leukemia inhibitory factor (LIF). Results: Compared to the vehicle, KRG or Rb1 increased myelin levels at week 6.5 but not 8, when measured by the LFB⁺ or GST-pi⁺ area within the corpus callosum. The levels of oligodendrocyte precursor cells, astrocytes, and microglia were high at week 5, and reduced afterwards but not changed by KRG or Rb1. In primary oligodendrocyte cultures, KRG or Rb1 increased expression of myelin genes, ER stress markers, and antioxidants. Interestingly, under cuprizone treatment, elevated ER stress markers were counteracted by KRG or Rb1. Under rotenone treatment, reduced myelin gene expressions were recovered by Rb1. In primary astrocyte cultures, KRG or Rb1 decreased LIF expression. Conclusion: KRG and Rb1 may improve myelin regeneration during the remyelination phase in vivo, potentially by directly promoting myelin gene expression.

• 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.

• Biomolecules & Therapeutics
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• v.27 no.2
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• pp.152-159
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• 2019

Multiple sclerosis (MS) is an autoimmune disease characterized by progressive neuronal loss, neuroinflammation, axonal degeneration, and demyelination. Previous studies have reported that 6-shogaol, a major constituent of ginger (Zingiber officinale rhizome), and its biological metabolite, 6-paradol, have anti-inflammatory and anti-oxidative properties in the central nervous system (CNS). In the present study, we investigated whether 6-shogaol and 6-paradol could ameliorate against experimental autoimmune encephalomyelitis (EAE), a mouse model of MS elicited by myelin oligodendrocyte glycoprotein ($MOG_{35-55}$) peptide immunization with injection of pertussis toxin. Once-daily administration of 6-shogaol and 6-paradol (5 mg/kg/day, p.o.) to symptomatic EAE mice significantly alleviated clinical signs of the disease along with remyelination and reduced cell accumulation in the white matter of spinal cord. Administration of 6-shogaol and 6-paradol into EAE mice markedly reduced astrogliosis and microglial activation as key features of immune responses inside the CNS. Furthermore, administration of these two molecules significantly suppressed expression level of tumor necrosis $factor-{\alpha}$, a major proinflammatory cytokine, in EAE spinal cord. Collectively, these results demonstrate therapeutic efficacy of 6-shogaol or 6-paradol for EAE by reducing neuroinflammatory responses, further indicating the therapeutic potential of these two active ingredients of ginger for MS.

• 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.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.27 no.5
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• pp.415-423
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• 2005

Distraction osteogenesis (DO) is frequently used technique in reconstruction of bony defects resulted from tumor resection, congenital deformity, and trauma in the maxillofacial region. Although the histologic and ultrastructural changes associated with distraction osteogenesis have been extensively described, the exact changing of the surrounding tissues, such as nerve tissues, were still unclear. This study observed the histological changes and the expression of nerve growth factor (NGF) in the inferior alveolar nerve (IAN) after distraction osteogenesis. Unilateral mandibular distraction (0.5 mm twice per day for 10 days) was performed in eight mongrel dogs. Two animals were sacrificed at 7, 14, 28 and 56 days after completion of distraction, respectively. The distracted IAN and contralateral control nerve were harvested and processed for histological and innunohistochemical examinations. The signs of acute nerve injuries, such as demyelination and partial discontinuation of nerver fiber, were observed in the distracted IAN on 7 and 14 days after distraction. The initial remyelination and regeneration of distracted IAN were showed at 14 days after completion of distraction. At 56 days later, the histologic features of distracted IAN was similar to those of the normal control IAN. The expression of NGF was significantly increased in most distracted nerve tissues on 7, 14 and 28 days after distraction. On 56 days after distraction, the expression of NGF returned to the normal level. This study suggested that the acute IAN injury caused by mandibular distraction were mostly recovered during consolidation period. The NGF was seemed to be induced from Schwann cell and damaged nerve tissues, and it may have important roles in the initial healing of damaged nerves.

• Science of Emotion and Sensibility
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• v.7 no.2
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• pp.179-186
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• 2004

Acute spinal cord injury can produce neurologic injury with many physical, psychological and social ramifications. It has been shown that two separate components combine to produce neurologic damage in acute spinal cord injury : the primary and secondary injuries. The primary mediators of spinal cord injury include the actual mechanical tissue disruption which is a passive process that occurs immediately following the trauma. A secondary injury cascade follows which appears mediated by cellular and molecular processes working through complex mechanisms. Both the primary and secondary injury cascades produce cell death both in neuronal and supporting cell tissues. Recovery from central nervous system(CNS) disorders is hindered by the limited ability of the vertebrate CNS to regenerate injured cells, replace damaged myelin sheath, and re-establish functional neuronal connections. Of many CNS disorders including multiple sclerosis, stroke, and other trauma, spinal cord injury is one of the important diseases because of the direct association with the functional loss of the body. Previous studies suggest that substantial recovery of function might be achieved through regeneration of lost neuronal cells and remyelination of intact axon in spinal cord injury which is occurred frequently. As a therapeutic approach in spinal cord injury, recently, cell transplantation provides a potential solution for the treatment of spinal cord injury. This review describes the characteristics of spinal cord injury and presents some evidence supporting functional recovery after cell transplantation following spinal cord injury.

• The Korean Journal of Pain
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• v.14 no.1
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• pp.83-92
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• 2001

Background: This study was undertaken to observe the functional changes of the hind limb and histopathological changes in the sciatic nerve after an injection of alcohol or phenol, which are commonly used neurolytic agents, highlighting the time of recovery. Methods: Forty-eight Sprague-Dawley rats weighing 200-300 g were used for the experiment. Histopathological changes under the electron microscope, were observed in the distal part of the sciatic nerve, into which 0.1 ml of alcohol or phenol was injected. This was severed in 3 rats of each group at 10 minutes, 1 hour, 24 hours, 3 days, 1, 2, 4 and 6 weeks later. The functional changes in the hind limbs were observed for 6 weeks by noting their walking pattern. Results: Following the injection of alcohol or phenol into the right sciatic nerve, the right hind limb showed a severe pronounced motor weakness and obvious gait changes. About 2 weeks later, gradual improvement of gait changes began, and after 6 weeks, the motor weakness and gait changes were no longer perceptible in both groups. The findings of any histopathological change were similar in both alcohol or phenol groups. At 10 minutes after injection, destructive lesions were confined to the unmyelinated fibers and the myelin sheath of small the myelinated fibers. On the 3rd day and at 1 week, pathologic changes in axonal fibers and Schwann cells were in being phagocytized in spite of myelin restitution. From 2 to 4 weeks, axonal regeneration and remyelination appeared at the same time a myelin disintegration and axonolysis. At 6 weeks, neural regeneration was similar to that of the contralateral control group. Conclusions: These results suggest that functional and histopathological changes, after injection of neurolytics into the peripheral nerves, are quite similar in both alcohol and phenol groups. The progression of functional and histopathological changes become more obvious according to the time interval following the injection. Consequently, side effects that develop following the use of alcohol or phenol may begin to improve around the time that nerve regeneration occurs, i.e., two to four weeks later.