• 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.

• Journal of Korean Neurosurgical Society
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• v.30 no.2
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• pp.168-172
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• 2001

Objective : The authors have studied the clinical outcome of patients with diffuse axonal injuries(DAI) to evaluate the prognostic value of gradient-echo MR imaging findings. Materials and Methods : From March 1995 to March 1998, there were nineteen patients with DAI whose initial Glasgow coma scales were eight or less. Authors divided them into two groups according to Glasgow outcome scales ; those patients with GOS 3 or less(group A ; 9) and those with 4 or more(group B ; 10). We subdivided the lesions as superficial and deep lesion, and analyzed the numbers, anatomical loci of the lesions on the gradient echo images of each group. Results : Mean numbers of the lesions were 15 per case in group A(135/9) and 10 in group B(100/10). The common loci involved in DAI were cerebral cortex, brain stem, and corpus callosum. Cortical lesions were 31.1% in group A(42/135) and 47% in group B(47/100). Brain stem lesions were 25.9%(35/135) and 15%(15/100) each. Callosal lesions were 31.1%(26/135) and 13%(13/100) each. The frequency of callosal and brain stem lesions was significantly different between two groups(p<0.05). We divided callosal lesions as genu, body, and splenium and body lesions as anterior, middle, posterior, but no significant topographical difference of lesions was observed between two groups. Deep lesions were observed more frequently in group A(58.5%, 79/135) than group B(36%, 36/100). Conclusion : The poor outcome group showed more numbers of lesion and more frequent involvement of brain stem and corpus callosum than favorable outcome group. Gradient-echo MR imaging seems to have predictive value for clinical outcome in patients with DAI.

• The Journal of Internal Korean Medicine
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• v.31 no.4
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• pp.763-774
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• 2010

Objectives : In condition of brain infarction, irreversible axon damage occurs in central nerve system(CNS), because gliosis becomes physical and mechanical barrier to axonal regeneration. Reactive gliosis induced by ischemic injury such as middle cerebral artery occlusion is involved with up-regulation of GFAP and CD81. The current study is to examine the effect of the Uncariae Ramulus et Uncus on CD81 and GFAP expression in the rat brain following middle cerebral artery occlusion. Methods : In order to study ischemic injuries on brain, infarction was induced by middle cerebral artery occlusion(MCAO) using insertion of a single nylon thread, through the internal carotid artery, into a middle cerebral artery. Cresyl violet staining, cerebral infarction size measurement, immunohistochemistry and microscopic examination were used to detect the expression of CD81 and GFAP and the effect on the infarct size and pyramidal cell death in the brain of the rat with cerebral infarction induced by MCAO. Results : The following results were obtained 1. Measuring the size of cerebral infartion induced by MCAO in the rat after injection of Uncariae Ramulus et Uncus showed the size was decreased. 2. Intravenous injection of Uncariae Ramulus et Uncus showed pyramidal cell death protection in the hippocampus in the MCAO rat. 3. Water extract injection of Uncariae Ramulus et Uncus decreased GFAP expression significantly in the MCAO rat. 4. Uncariae Ramulus et Uncus water extract decreased CD81 expression in the MCAO rat. 5. The administration of water extract of Uncariae Ramulus et Uncus induced up-regulation of c-Fos expression significantly compared with MCAO. 6. The admistration of water extract of Uncariae Ramulus et Uncus increased ERK expression significantly compared with MCAO. Conclusion : We observed that Uncariae Ramulus et Uncus could suppress the reactive gliosis, which disturbs the axonal regeneration in the brain of the rat with cerebral infaction after MCAO by controlling the expression of CD81 and GFAP. The effect may be modulated by the up-regulation of c-Fos and ERK. These results suggest that Uncariae Ramulus et Uncus can be a candidate to regenerate CNS injury.

• Journal of Korean Neurosurgical Society
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• v.29 no.2
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• pp.210-216
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• 2000

Objectives : Head injury is one of the common causes of death in the industrialized countries, and it is a common cause of subarachnoid hemorrhage. Recently, traumatic subarachnoid hemorrhage(TSAH) has been considered as a major prognostic factor. Some suggested that a certain vasodilating agent may be effective to treat or prevent the secondary brain injury due to vasospasm from TSAH. The role of TSAH is not yet fully solved. The prognosis and clinical significance of the TSAH was evaluated. Methods : A retrospective study was performed. A total of 573 consecutive patients with head injury admitted to our institute from January 1996 to December 1997 were examined with respect to outcome and clinical features. In all patients, computerized tomographic scanning was done within 2 days after the injury. Results : TSAH was found in 68 patients(11.9%). The outcome at discharge of the patients without TSAH was favorable(good recovery and moderate disability) in 84.8%, unfavorable(severe disability and vegetative state) in 8.6%, and the mortality rate 6.7%. However, the outcome was favorable in 51.5%, unfavorable in 20.6%, and the mortality rate 27.9% in patients with TSAH. Although the outcome of the patients with thick TSAH was worse than that of the patients with scanty TSAH, the difference was not statistically significant. The difference of the outcome in patients with TSAH according to the location also lacked statistical significance. TSAH was more common in patients with age of 40 years or more, and patients with low Glasgow coma scores. Patients with TSAH had abnormal pupillary responses, diffuse axonal injuries, intubations and operative interventions more frequently than patients without TSAH. Conclusion : These results strongly suggest that the TSAH per se did not worsen the prognosis. However, it represented the injury to be more severe.

• Journal of Korean Neurosurgical Society
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• v.29 no.10
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• pp.1296-1302
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• 2000

Objective : Traumatic brain injury including diffuse axonal injury has been shown to result in a decrease in brainfree magnesium concentration, an endogenous inhibitor of calcium entry into neuron, that is associated with the development of neurological motor deficits. The goal of this study is to establish the therapeutic window during which the therapy with $MgSO_4$ and/or hypothermia improve damaged neurons by TUNEL stain. Method : Moderate brain injury was induced in 64 adult Sprague-Dawley rats, weighing 350 to 450gm each, by using a simple weight-drop device(Marmarou model). The animals were randomly assigned to four groups(sixteen rats each, a control group, a group treated with $MgSO_4$, a group treated with hypothermia, and a group treated with $MgSO_4$ and hypothermia) and the rats in each group were sacrificed and studied after 12 hrs, 24 hrs, 1 wk, and 2 wks after insult. In hypothermic group, these rats were subjected to hypothermia after injury, with their rectal temperatures maintained at $32^{\circ}C$ for 1 hour. After 1-hour period of hypothermia, rewarming to normothermic level was accomplished over 30-minute period. In the groups treated $MgSO_4$, hypothermia and $MgSO_4$ were subsequently treated with $MgSO_4$($750{\mu}moles/kg$) infused intra-muscularly at 30 minutes after trauma. Result : In all treated groups, a significant reduction in TUNEL positive cells was found in comparison with the control group each time(p<0.001). Between treatment groups, No differnce was seen 12hrs, 24hrs, and 1wk. However, hypothermic group treated with or without $MgSO_4$ showed more significant reduction in apoptotic cells than group treated with $MgSO_4$ 2 weeks after trauma(p<0.05). However, hypothermic group treated with $MgSO_4$ showed no significant reduction in apoptotic cells compared with hypothermic group(p>0.05). Conclusion : These findings suggest that both hypothermia and $MgSO_4$ significantly improve pathological changes. Otherwise simultaneously $MgSO_4$ and hypothermia treatment groups is failed to provide additional neuroprotection. These results may be relevant to the design of future clinical trials of therapeutic hypothermia and $MgSO_4$ for traumatic brain injury.

• Physical Therapy Korea
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• v.9 no.3
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• pp.67-76
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• 2002

We report the reorganization of motor network resulted from intensive unilateral coordination training and the effect of cross education on the untrained side in patient with traumatic brain injury using functional magnetic resonance imaging (fMRI). A 22 year-old male patient who had suffered from diffuse axonal injury for 58 months showed coordination deficit in the left hand at initial examination. Intensive motor training including complex finger movements and coordination activities using a metronome was introduced to the patient 4 hours per day for a week. FMRI was performed on a 3T ISOL Forte scanner. All functional images were analyzed using SPM-99 software. Hand function was improved after training not only in the trained left hand, but also in the untrained right hand. There was no activation in the right primary motor area (M1) during left hand movement before training whereas robust activation of left M1 was demonstrated by the right hand movement. Profuse activation of bilateral prefrontal lobes was seen during both hand movements before training. After training of left hand, right M1 became prominently activated during the left hand motion. The activation of bilateral prefrontal lobes disappeared after training not only for the left hand movement but also for the right, which clearly demonstrated the effect of cross education. This case report demonstrated the learning-dependent reorganization of the M1 and the effect of cross education.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.3
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• pp.285-296
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• 1997

Injury to brain transforms resting astrocytes to their reactive form, the hallmark of which is an increase in glial fibrillary acidic protein (GFAP), the major intermediate filament protein of their cell type. The overall glial response after brain injury is referred to as reactive gliosis. Glial-neuronal interaction is important for neuronal migration, neurite outgrowth and axonal guidance during ontogenic development. Although much attention has been given to glial regulation of neuronal development and regeneration, evidences also suggest a neuronal influence on glial cell differentiation, maturation and function. The aim of the present study was to analyze the effects of glial-hippocampal neuronal co-culture on GFAP expression in the co-cultured astrocytes. The following antibodies were used for double immunostaining chemistry; mouse monoclonal antibodies for confirm neuronal cells, rabbit anti GFAP antibodies for confirm astrocytes. Primary cultured astrocytes showed the typical flat polygonal morphology in culture and expressed strong GFAP and vimentin. Co-cultured hippocampal neurons on astrocytes had phase bright cell body and well branched neurites. About half of co-cultured astrocytes expressed negative or weak GFAP and vimentin. After 2 hour glutamate (0.5 mM) exposure of glial-neuronal co-culture, neuronal cells lost their neurites and most of astrocytes expressed strong CFAE and vimentin. In Western blot analysis, total GFAP and vimentin contents in co-cultured astrocytes were lower than those of primary cultured astrocytes. After glutamate exposure of glial-neuronal co-culture, GFAP and vimentin contents in astrocytes were increased to the level of primary cultured astrocytes. These results suggest that neuronal cell decrease GFAP expression in co-cultured astrocytes and hippocampal neuronal-glial co-culture can be used as a reactive gliosis model in vitro for studying GFAP expression of astrocytes.

• BMB Reports
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• v.47 no.12
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• pp.679-684
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• 2014

GM-CSF plays a role in the nervous system, particularly in cases of injury. A therapeutic effect of GM-CSF has been reported in rat models of various central nervous system injuries. We previously showed that GM-CSF could enhance long-term recovery in a rat spinal cord injury model, inhibiting glial scar formation and increasing the integrity of axonal structure. Here, we investigated molecular the mechanism(s) by which GM-CSF suppressed glial scar formation in an in vitro system using primary astrocytes treated with TGF-${\beta}$. GM-CSF repressed the expression of chondroitin sulfate proteoglycan (CSPG) core proteins in astrocytes treated with TGF-${\beta}$. GM-CSF also inhibited the TGF-${\beta}$-induced Rho-ROCK pathway, which is important in CSPG expression. Finally, the inhibitory effect of GM-CSF was blocked by a JAK inhibitor. These results may provide the basis for GM-CSF's effects in glial scar inhibition and ultimately for its therapeutic effect on neural cell injuries.

• Proceedings of the Korean Society of Medical Physics Conference
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• 2003.09a
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• pp.73-73
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• 2003

Purpose: To determine the motor cortex dysfunction in hemiparetic patients due to deep intracerebral hematoma, authors performed proton magnetic resonance spectroscopy (lH MRS) for the evaluation of biochemical changes in the cortex on affected hemisphere according to axonal injury at the level of internal capsule. Methods: Ten control subjects and 14 patients with documentable hemiparesis of varying severity hemiparesis were included. All the hemiparesis was caused by deep intracerebral hematoma (putaminal and thalamic hemorrhage). In vivo 1H MRS study was performed on a 3T MRI/MRS system using STEAM sequence. As a single-voxel technique, Spectral parameters were: 20 ms TE, 2000 ms TR, 128 averages, 2500 Hz spectral width, and 2048 data points. Results: We found that the mean N-acetylaspartate (NAA)/phosphocreatine (Cr) and NAA/choline (Cho) ratios were significantly decreased in the motor cortex of the hemiparesis patients compared with control subjects. Conclusions: 1H MRS examinations of the motor cortex might help to differentiate distinct clinical entities of hemiparesis and to monitor pharmacological effects in therapeutic trials, providing a quantitative biological marker for motor neuron dysfunction. Acknowledgement: This study was supported by a grant of the Center for Functional and Metabolic Imaging Technology, Ministry of Health & Welfare, Republic of Korea. (02-PJ3-PG6-EV07-000).

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.6
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• pp.405-411
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• 2012

The spontaneous axon regeneration of damaged neurons is limited after spinal cord injury (SCI). Recently, mesenchymal stem cell (MSC) transplantation was proposed as a potential approach for enhancing nerve regeneration that avoids the ethical issues associated with embryonic stem cell transplantation. As SCI is a complex pathological entity, the treatment of SCI requires a multipronged approach. The purpose of the present study was to investigate the functional recovery and therapeutic potential of human MSCs (hMSCs) and polymer in a spinal cord hemisection injury model. Rats were subjected to hemisection injuries and then divided into three groups. Two groups of rats underwent partial thoracic hemisection injury followed by implantation of either polymer only or polymer with hMSCs. Another hemisection-only group was used as a control. Behavioral, electrophysiological and immunohistochemical studies were performed on all rats. The functional recovery was significantly improved in the polymer with hMSC-transplanted group as compared with control at five weeks after transplantation. The results of electrophysiologic study demonstrated that the latency of somatosensory-evoked potentials (SSEPs) in the polymer with hMSC-transplanted group was significantly shorter than in the hemisection-only control group. In the results of immunohistochemical study, ${\beta}$-gal-positive cells were observed in the injured and adjacent sites after hMSC transplantation. Surviving hMSCs differentiated into various cell types such as neurons, astrocytes and oligodendrocytes. These data suggest that hMSC transplantation with polymer may play an important role in functional recovery and axonal regeneration after SCI, and may be a potential therapeutic strategy for SCI.