• Journal of Korean Medical classics
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• v.20 no.2
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• pp.53-59
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• 2007

In Oriental medicine, different suggestions regarding how cerebrovascular accident(CVA) may develop have been offered by several physicians. In Jin(金)Yuan(元) dynasty, Liu Wan Su(劉完素) asserted that CVA was not developed by external PungSa(風邪) but internal HwaYul, which was noted in the "SoMunHyunKiWonByungSik". To verify experimentally Liu's HwaYul theory in rats, normothermic control group (37$^{circ}C$) and hypothermic test group (32$^{circ}C$) were subjected to transient middle cerebral artery occlusion(MCAO) of 1hour. In 7days after MCAO, the rats were sacrified and the volume of infarct and the size of edema were measured. The present findings expand our understanding of the pathophysiology as to the CVA which is related to the HwaYul theory.

• The Journal of Korean Medicine
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• v.20 no.4
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• pp.82-92
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• 2000

The purpose of the present study was to explore the proper method for animal stroke model of Oriental medicine To this end, brain ischemia was induced by distal middle cerebral artery occlusion(dMCAO) and proximal middle cerebral artery occlusion(pMCAO) and evaluated with the method of Triphenyl Tetrazolium Chloride (TTC) staining and Swimming Behavior Test. Results demonstrated that first, infarct size and volume of pMCAO group were significantly bigger that those of dMCAO group. Second, analysis of swimming behavior test revealed that the percentage of left turning angles of pMCAO was significantly bigger than that of dMCAO. Third, during swimming behavior test, there were peculiar traces of small successive circles that represent motor dysfunction and conscious disturbance among dMCAO group. The results of the study thus indicate that non-invasive intraluminal method of pMCAO was the appropriate animal stroke model for Oriental medicine in the light of brain ischemia as hemiplesia and conscious disturbance.

• Journal of Korean Neurosurgical Society
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• v.65 no.6
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• pp.816-824
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• 2022

Objective : Emergency superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis in patients with large vessel occlusion who fails mechanical thrombectomy or does not become an indication due to over the time window can be done as an alternative for blood flow restoration. The authors planned this study to quantitatively measure the degree of improvement in cerebral perfusion flow using perfusion magnetic resonance imaging (MRI) after bypass surgery and to find out what factors are related to the outcome of the bypass surgery. Methods : For a total of 107 patients who underwent emergent STA-MCA bypass surgery with large vessel occlusion, the National Institute of Health stroke scale (NIHSS), modified Rankin score (mRS), infarction volume, and hypoperfusion area volume was calculated, the duration between symptom onset and reperfusion time, occlusion site and infarction type were analyzed. After emergency STA-MCA bypass, hypoperfusion area volume at post-operative 7 days was calculated and analyzed compared with pre-operative hypoperfusion area volume. The factors affecting the improvement of mRS were analyzed. The clinical status of patients who underwent emergency bypass was investigated by mRS and NIHSS before and after surgery, and changes in infarct volume, extent, degree of collateral circulation, and hypoperfusion area volume were measured using MRI and digital subtraction angiography (DSA). Results : The preoperative infarction volume was median 10 mL and the hypoperfusion area volume was median 101 mL. NIHSS was a median of 8 points, and the last normal to operation time was a median of 60.7 hours. STA patency was fair in 97.1% of patients at 6 months follow-up DSA and recanalization of the occluded vessel was confirmed at 26.5% of patients. Infarction volume significantly influenced the improvement of mRS (p=0.010) but preoperative hypoperfusion volume was not significantly influenced (p=0.192), and the infarction type showed marginal significance (p=0.0508). Preoperative NIHSS, initial mRS, occlusion vessel type, and last normal to operation time did not influence the improvement of mRS (p=0.272, 0.941, 0.354, and 0.391). Conclusion : In a patient who had an acute cerebral infarction due to large vessel occlusion with large ischemic penumbra but was unable to perform mechanical thrombectomy, STA-MCA bypass could be performed. By using time-to-peak images of perfusion MRI, it is possible to quickly and easily confirm that the brain tissue at risk is preserved and that the ischemic penumbra is recovered to a normal blood flow state.

• The Korea Journal of Herbology
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• v.21 no.2
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• pp.151-158
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• 2006

Objectives : The purpose of the present study is to observe the neuroprotective effect of the $NeuBo153^{\circledR}$ on transient focal cerebral ischemia in rats. Methods : $NeuBo153^{\circledR}$ was made by mixing the herbs, mainly the root of Panax ginseng, the root of Rehmannia glutinosa and Poria cocos, the stem bark of Acanthopanax senticosus, the root of Scutellaria baicalensis and Mel, and heating for 96 hours. Transient Focal cerebral ischemia (2 h of ischemia, 22 h of reperfusion) was induced by intraluminal suture method with SD rats. Sensory motor function was tested by rotarod test, prehensile traction test, beam balance test and foot fault test at 24 h after ischemia. The brain slices were stained by 2% 2, 3, 5-triphenyltetrazolium chloride and the infarct volume was measured by graphic analyzer at 24 h after ischemia. Results : $NeuBo153^{\circledR}$ treated group did not show significant differences compared with vehicle treated group in body temperature. Oral administration of $NeuBo153^{\circledR}$ reduced brain infarct volume by 29.7% compared with vehicle treated group. $NeuBo153^{\circledR}$ also showed protective effects on sensory motor functional deficits. Conclusion : $NeuBo153^{\circledR}$ treatment reduced brain damage and improved functional deficits induced by MCAo. It showed neuroprotective effects even when treatment was relayed 2 h after injury. Further research is required to evaluating long term functional recovery am accurate therapeutic range and mechanisms.

• Journal of Life Science
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• v.30 no.11
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• pp.939-946
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• 2020

Stroke is one of the leading causes of neurological disability worldwide and stroke patients exhibit a range of motor, cognitive, and psychiatric impairments. GPR88 is an orphan G protein-coupled receptor (GPCR) that is highly expressed in striatal medium spiny neurons; its deletion results in poor motor coordination and motor learning. There are currently no studies on the involvement of GPR88 in stroke or in post-stroke brain function recovery. In this study, we found a decrease in GPR88 protein and mRNA expression levels in an ischemic mouse model using Western blot and real-time PCR, respectively. In addition, we observed that, among the three types of cells derived from the brain (brain microvascular endothelial cells, BV2 microglial cells, and HT22 hippocampal neuronal cells), the expression of GPR88 was highest in HT22 neuronal cells, and that GPR88 expression was downregulated in HT22 cells under oxygen-glucose deprivation (OGD) conditions. Moreover, pretreatment with RTI- 13951-33 (10 mg/kg), a brain-penetrant GPR88 agonist, ameliorated brain injury following ischemia, as evidenced by improvements in infarct volume, vestibular-motor function, and neurological score. Collectively, our results suggest that GPR88 could be a potential drug target for the treatment of central nervous system (CNS) diseases, including ischemic stroke.

• The Korea Journal of Herbology
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• v.32 no.1
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• pp.25-31
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• 2017

Objectives : Mori Radicis Cortex (MRC), the root epidermis of Morus alba L., has been traditionally used to treat lung-related diseases in Korean Medicine. The common of MRC is Mulberry bark Morus bark, and it's pharmaceutical properties and taste are known as sweet and cold, and it promotes urination and reduce edema by reducing heat from the lungs and soothe asthma. In the present study, anti-apoptotic mechanism of MRC in middle cerebral artery occlusion (MCAO) model in mice. Methods : Two-hundred grams of MRC was extracted with methanol at room temperature for 5 days, and this was repeated one time. After filtration, the methanol was removed using vacuum evaporator, then stored at $-20^{\circ}C$ until use. C57BL/6 male mice were housed in an environment with controlled humidity, temperature, and light cycle. In order to determine beneficial effects of MRC on ischemia induced brain damage, infarct volume, neurological deficit scores, activities of several apoptosis-related proteins such as caspase-8, -9, Bcl-xL in MCAO-induced brains of mice were analyzed. Mice in MRC-treated groups were orally administered 30, 100, or 300 mg/kg of body weight for three consecutive days before commencing the MCAO procedure. Results : Pre-treatment of MRC significantly reduced infarct volume in MCAO subjected mice applied with 300 mg/kg of MRC methanol extract, and MRC effectively inhibited Bcl-xL reduction and caspase-9 activation caused by MCAO-induced brain damage. Conclusions : MRC showed neuro-protective effects by regulating apoptosis-related protein signals, and it can be a potential candidate for the therapy of ischemia-induced brain damage.

• The Korea Journal of Herbology
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• v.27 no.6
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• pp.71-76
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• 2012

Objectives : The purpose of this study was to evaluate the neuroprotective effect of Pueraria lobata extract on focal cerebral ischemia in mice. Methods : Focal cerebral ischemia was induced by occlusion of the right middle cerebral artery using the intraluminal filament model. ICR male mice underwent 90 minutes of middle cerebral artery occlusion (MCAo) followed by 24 hours of reperfusion. Mice were administered Pueraria lobata extract orally at the dose of 300mg/kg just prior to reperfusion. Rotarod test and balance beam test were practiced to assess sensory-motor function 23 hours after MCAo. In rotarod test, the latency to fall on the accelerating rotarod was recorded for 5 min. In balance beam test, the score was graded according to number of slips and latency to cross. The infarct volume was measured 24 hours after MCAo using 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining. Results : Pueraria lobata extract treated group showed significant reduction in infarct volume by 27.3% compared to control group (p<0.05). In rotatod test, it also showed significant extension of latency time compared to control group ($67.82{\pm}15.08$ vs. $5.62{\pm}1.06$, p<0.001). In contrast to performance in rotarod test, that in balance beam test did not improve with Pueraria lobata extract treatment. Conclusions : We conclude that Pueraria lobata extract has a significant neuroprotective effect and reduces damage of sensory-motor function in MCAo model. These findings suggest that Pueraria lobata could be a potent neuroprotective agent.

• Archives of Pharmacal Research
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• v.27 no.9
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• pp.930-936
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• 2004

Wogonin (5,7-dihydroxy-8-methoxyflavone), an active component originated from the root of Scutellaria baicalensis Georgi, has been reported to possess antioxidant and anti-inflamma-tory properties. In this study, we investigated the neuroprotective effect of wogonin in a focal cerebral ischemia rat model. Wogonin markedly reduced the infarct volume after 2 h middle cerebral artery occlusion followed by 22 h reperfusion. Wogonin decreased the production of nitric oxide and inflammatory cytokines such as TNF-$\alpha$ and IL-6 in lipopolisaccharide-stimu-lated microglial cells. While wogonin reduced the activity of NF-$textsc{k}$B, it did not change the activ-ity of mitogen-activated protein kinases family members, p38, ERK and JNK. The lipopolisaccharide-stimulated production of NO and cytokines was significantly blocked by vari-ous kinds of NF-$textsc{k}$B inhibitors such as N-acetyl cysteine, pyrrolidinedithiocarbamate and MG-132. The data may indicate that wogonin has neuroprotective effect by preventing the over-activation of microglial cells, possibly by inactivating NF-$textsc{k}$B signaling pathway

• The Journal of Korean Medicine
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• v.30 no.6
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• pp.53-68
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• 2009

Objectives: This study demonstrates the neurological effects of Bojungikki-tang and Bojungikki-tang-gamibang on the focal cerebral ischemia of rats with ischemic damage caused by middle cerebral artery occlusion (MCAO). Methods: Rats were treated with Bojungikki-tang and Bojungikki-tang-gamibang extracts for about five days after MCAO, and the size and volume of cerebral infarction and the ratio of cerebral edema were observed. From the immunohistochemical view, significant changes of outbreak of Bax, Bcl-2, c-Fos, HSP72, and iNOS were observed in the brain tissues. Results: Bojungikki-tang repressed only brain edema and iNOS revelation led by focal cerebral ischemia, when considering significance. In contrast, Bojungikki-tang-gamibang demonstrated significant suppression of cerebral infarction, brain edema, Bax, c-Fos, HSP72, and iNOS induced by focal cerebral ischemia. Conclusions: Bojungikki-tang is considered functional treatment for cerebral ischemic damage; it can be effective to relieve secondary brain edema and immune response. Bojungikki-tang-gamibang can have a direct function to alleviate brain infarct and to control the natural death of nerve cells which cerebral ischemic damage brings about.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.6
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• pp.1411-1414
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• 2007

According to the report of Korea National Statistical Office in 2007, cerebral vascular disease is second cause of deaths in Korean. Cerebral ischemia is one of the main reason of cerebral vascular diseases. To evaluate the neuroprotective effect of heyneanol A against cerebral ischemia, we used the middle cerebral artery occlusion model (MCAO). Heyneanol A from root of vitis amurensis Rup is a tetramer of resveratrol as known anti-oxidant and anti-cancer agent. Although the effects of resveratrol in the various fields have been well established, little is known of the effects of heyneanol A. In this study, heyneanol A reduced infarction and edema volume by 33.5% and 57% compared with control groups (vehicle), respectively. Also, neurological score was decreased by heyneanol A. It's effects were more potent than resveratol. Taken together, these results exerted that heyneanol A has a neuroprotective effect against cerebral ischemia.