• Journal of the Korean Society of Physical Medicine
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• v.7 no.1
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• pp.11-20
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• 2012

Purpose : This study is intended to examine the repetitive transcranial magnetic stimulation on cognitive function in the focal ischemic stroke rat model. Methods : This study selected 30 Sprague-Dawley rats of 8 weeks. The groups were divided into two groups and assigned 15 rats to each group. Control group: Non-treatment after injured by focal ischemic stroke; Experimental group: application of repetitive transcranial magnetic stimulation(0.1 Tesla, 25 Hz, 20 min/time, 2 times/day, 5 days/2 week) after injured by focal ischemic stroke. To assess the effect of rTMS, the passive avoidance test, spatial learning and memory ability test were analyzed at the pre, 1 day, $7^{th}$ day, $14^{th}$ day and immunohistochemistric response of BDNF were analyzed in the hippocampal dentate gyrus at $7^{th}$ day, $14^{th}$ day. Results : In passive avoidance test, the outcome of experimental group was different significantly than the control group at the $7^{th}$ day, $14^{th}$ day. In spatial learning and memory ability test, the outcome of experimental group was different significantly than the control group at the $7^{th}$ day, $14^{th}$ day. In immunohistochemistric response of BDNF in the hippocampal dentate gyrus, experimental groups was more increased than control group. Conclusion : These result suggest that improved cognitive function by repetitive transcranial magnetic stimulation after focal ischemic stroke is associated with dynamically altered expression of BDNF in hippocampal dentate gyrus and that is related with synaptic plasticity.

• Journal of Acupuncture Research
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• v.27 no.4
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• pp.29-38
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• 2010

Objectives : The purpose of the study is to determine the neuroprotective effect of modified Boyanghwano-tang(mBHT), a traditional Korean medicine, on the transient focal cerebral ischemia in rats. Methods : Focal ischemia and reperfusion were induced by middle cerebral artery occlusion(MCAO) for 90 min, followed by 144 h reperfusion in rats. mBHT(200mg/kg body weight, p.o.) was administrated in rats once a day during reperfusion. At the end of treatment, brain infarction was measured by TTC staining, and histological change was observed by H&E staining. The expressions of Bax, Bcl-2 and cytochrome c in ischemic brains were determined by immunofluorescent analysis. Results : mBHT significantly reduced the cerebral infarct volumes of the MCAO rats. mBHT also attenuated the neuronal cell death and the expressions of pro-apoptotic molecules, bax and cytochrome c in ischemic brains. Further, mBHT significantly increased the survival time of ischemeic rats and the expression of anti-apoptotic molecule, Bcl-2 in ischemic brains. Conclusions : Our results suggest that mBHT is neuroprotective and may prove to be useful adjunct in the treatment of ischemic stroke.

• Korean Journal of Acupuncture
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• v.35 no.4
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• pp.187-202
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• 2018

Objectives : Non-invasive transcranial electrical stimulation is one of therapeutic interventions to change in neural excitability of the cortex. Transcranial electro-acupuncture (TEA) can modulate brain functions through changes in cortical excitability as a model of non-invasive transcranial electrical stimulation. Some composites of fermented Scutellaria baicalenis (FSB) can activate intercellular signaling pathways for activation of brain-derived neurotrophic factor that is critical for formation of neural plasticity in stroke patients. This study was aimed at evaluation of combinatory treatment of TEA and FSB on behavior recovery and cortical neural excitability in rodent focal stroke model. Methods : Focal ischemic stroke was induced by photothrombotic injury to the motor cortex of adult rats. Application of TEA with 20 Hz and $200{\mu}A$ in combination with daily oral treatment of FBS was given to stroke animals for 3 weeks. Motor recovery was evaluated by rotating bean test and ladder working test. Electrical activity of cortical pyramidal neurons of stroke model was evaluated by using multi-channel extracellular recording technique and thallium autometallography. Results : Compared with control stroke group who did not receive any treatment, Combination of TEA and FSB treatment resulted in more rapid recovery of forelimb movement following focal stroke. This combination treatment also elicited increase in spontaneous firing rate of putative pyramidal neurons. Furthermore expression of metabolic marker for neural excitability was upregulated in peri-infract area under thallium autometallography. Conclusions : These results suggest that combination treatment of TEA and FSB can be a possible remedy for motor recovery in focal stroke.

• Journal of Korean Neurosurgical Society
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• v.50 no.3
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• pp.173-178
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• 2011

Objective : The rat middle cerebral artery thread-occlusion model has been widely used to investigate the pathophysiological mechanisms of stroke and to develop therapeutic treatment. This study was conducted to analyze energy metabolism, apoptotic signal pathways, and genetic changes in the hippocampus of the ischemic rat brain. Methods : Focal transient cerebral ischemia was induced by obstructing the middle cerebral artery for two hours. After 24 hours, the induction of ischemia was confirmed by the measurement of infarct size using 2,3,5-triphenyltetrazolium chloride staining. A cDNA microarray assay was performed after isolating the hippocampus, and was used to examine changes in genetic expression patterns. Results : According to the cDNA microarray analysis, a total of 1,882 and 2,237 genes showed more than a 2-fold increase and more than a 2-fold decrease, respectively. When the genes were classified according to signal pathways, genes related with oxidative phosphorylation were found most frequently. There are several apoptotic genes that are known to be expressed during ischemic brain damage, including Akt2 and Tnfrsf1a. In this study, the expression of these genes was observed to increase by more than 2-fold. As energy metabolism related genes grew, ischemic brain damage was affected, and the expression of important genes related to apoptosis was increased/decreased.Conclusion : Our analysis revealed a significant change in the expression of energy metabolism related genes (Atp6v0d1, Atp5g2, etc.) in the hippocampus of the ischemic rat brain. Based on this data, we feel these genes have the potential to be target genes used for the development of therapeutic agents for ischemic stroke.

• The Journal of Internal Korean Medicine
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• v.31 no.2
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• pp.380-387
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• 2010

The ischemic penumbra represents part of the hypoperfused region associated with focal brain ischemia. A practical approach is to define this region as that portion of the ischemic territory that can potentially be salvaged by timely intervention. For the prevention and treatment of ischemic stroke, antithrombotic therapy is prescribed. But medication of antiplatelet agent is only validated as prevention effect. Cheonghyulgangki-tang has been used for cerebral apoplexy, hypertension, etc. In this case report, an acute ischemic stroke patient was treated with an antiplatelet agent named Plavix and Cheonghyulgangki-tang and remarkable reduction of ischemic portion in the brain CT was observed. The result of this case suggests that oriental medical therapy could be a safe and effective intervention in acute ischemic stroke.

• Journal of Life Science
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• v.29 no.11
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• pp.1258-1266
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• 2019

Yangkyuksanhwa-Tang (YKSH), consisting of nine different herbs, is commonly used in Soyangin-type individuals with stroke, based on the Sasang Constitution Theory in Korea. However, no evidence has yet confirmed a beneficial effect of YKSH in ischemic stroke treatment. In this study, we investigated the effects of YKSH on ischemic brain injury in a mouse model of cerebral ischemia. Focal cerebral ischemia in mice was induced by photothrombosis, and behavioral recovery was evaluated. Infarct volume, inflammation, and newly generated cells were evaluated by histology and immunochemistry. YKSH treatment resulted in a significant recovery from the motor impairments induced by focal cerebral ischemia, as determined with wire grip and rotarod tests. YKSH treatment also decreased the infarct volume and the number of cells positive for tumor necrosis factor-${\alpha}$ and myeloperoxidase when compared with a vehicle-treated control group. By contrast, YKSH treatment considerably increased the number of cells positive for glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1, as well as the number of cells doubly positive for Ki67/doublecortin when compared with the vehicle-treated group. These results suggest that YKSH treatment attenuated the infarct size by anti-inflammatory action, astrocyte and microglia activation, and neuronal proliferation, thereby facilitating neurofunctional recovery from a cerebral ischemic assault. YKSH could therefore be a potential treatment for neurofunctional restoration of the injured brains of patients with stroke.

• Biomolecules & Therapeutics
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• v.17 no.3
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• pp.270-275
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• 2009

Polyethylene glycol-conjugated hemoglobin (PEG-Hb) has been proposed as a blood substitute for transfusion due to their plasma expansion and oxygen transport capabilities. The protective effect of PEG-Hb on cerebral hypoxic-ischemic injury was investigated in neonatal hypoxia model and adult rat focal cerebral ischemia model. As intravenously administered 30 min before the onset of hypoxia, PEG-Hb markedly protected cerebral hypoxic injury in a neonatal rat hypoxia model. A similar treatment of PEG-Hb largely reduced the ischemic injury ensuing after 2-h middle cerebral artery occlusion followed by 22-h reperfusion. Consistently, neurological disorder was significantly improved by PEG-Hb. The results indicate that the pharmacological blockade of cerebral ischemic injury by using PEG-Hb may provide a useful strategy for the treatment of cerebral stroke.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.5
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• pp.275-280
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• 2008

A brief ischemic insult induces significant protection against subsequent massive ischemic events. The molecular mechanisms known as preconditioning (PC)-induced ischemic tolerance are not completely understood. We investigated whether kinetic changes of cyclooxygenase (COX)-2 during reperfusion time-periods after PC were related to ischemic tolerance. Rats were given PC by occlusion of middle cerebral artery (MCAO) for 10 min and sacrificed after the indicated time-periods of reperfusion (1, 2, 4, 8, 12, 18 or 24 h). In PC-treated rats, focal ischemia was induced by occlusion of MCA for 24 h and brain infarct volume was then studied to determine whether different reperfusion time influenced the damage. We report that the most significant protection against focal ischemia was obtained in rats with 8 h reperfusion after PC. Administration of indomethacin (10 mg/kg, oral) or rofecoxib (5 mg/kg, oral) 48 h prior to PC counteracted the effect of PC. Immunohistochemical analysis showed that COX-2 and HO-l protein were induced in PC-treated rat brain, which was significantly inhibited by rofecoxib. Taken together, we concluded that the kinetic changes of COX-2 expression during the reperfusion period after PC might be partly responsible for ischemic tolerance.

• Journal of Korean Neurosurgical Society
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• v.50 no.2
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• pp.89-94
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• 2011

Objective : D-dimer is a breakdown product of fibrin mesh after factor XIII stabilization. Previously, many authors have demonstrated a relationship between D-dimer level and stroke progression or type. This study aimed to investigate the relationship between D-dimer level and stroke volume. Methods : Between January 2008 and December 2009, we analyzed the D-dimer levels of 59 acute ischemic stroke patients in our neurosurgical department both upon admission and after seven days of initial treatment. Each patient's National Institute of Health Stroke Scale score, modified Rankin Scales score, Glasgow outcome score, and infarction volume were also evaluated. Results : Mean D-dimer level at admission was 626.6 ${\mu}g/L$ (range, 77-4,752 ${\mu}g/L$) and the mean level measured after seven days of treatment was 238.3 ${\mu}g/L$ (range, 50-924 ${\mu}g/L$). Mean D-dimer level at admission was 215.3 ${\mu}g/L$ in patients with focal infarctions, 385.7 ${\mu}g/L$ in patients with multiple embolic infarctions, 566.2 ${\mu}g/L$ in those with 1-19 cc infarctions, 668.8 ${\mu}g/L$ in 20-49 cc infarctions, 702.5 ${\mu}g/L$ in 50-199 cc infarctions, and 844.0 ${\mu}g/L$ in >200 cc infarctions (p=0.044). On the 7th day of treatment, the D-dimer levels had fallen to 201.0 ${\mu}g/L$, 293.2 ${\mu}g/L$, 272.0 ${\mu}g/L$, 232.8 ${\mu}g/L$, 336.6 ${\mu}g/L$, and 180.0 ${\mu}g/L$, respectively (p=0.530). Conclusion : Our study shows that D-dimer level has the positive correlation with infarction volume and can be use to predict infarction-volume.

• Journal of Korean Neurosurgical Society
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• v.55 no.3
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• pp.125-130
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• 2014

Objective : This study was conducted to elucidate neuroprotective effect of carnosine in early stage of stroke. Methods : Early stage of rodent stroke model and neuroblastoma chemical hypoxia model was established by middle cerebral artery occlusion and antimycin A. Neuroprotective effect of carnosine was investigated with 100, 250, and 500 mg of carnosine treatment. And antioxidant expression was analyzed by enzyme linked immunosorbent assay (ELISA) and western blot in brain and blood. Results : Intraperitoneal injection of 500 mg carnosine induced significant decrease of infarct volume and expansion of penumbra (p<0.05). The expression of superoxide dismutase (SOD) showed significant increase than in saline group in blood and brain (p<0.05). In the analysis of chemical hypoxia, carnosine induced increase of neuronal cell viability and decrease of reactive oxygen species (ROS) production. Conclusion : Carnosine has neuroprotective property which was related to antioxidant capacity in early stage of stroke. And, the oxidative stress should be considered one of major factor in early ischemic stroke.