• Molecular & Cellular Toxicology
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• v.4 no.3
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• pp.218-223
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• 2008

Oxidative stress is believed to contribute to the neuronal damage induced by cerebral ischemia/reperfusion injury. The present study was undertaken to evaluate the possible antioxidant neuroprotective effect of hydroxyfullerene (a radical absorbing cage molecule) against neuronal death in hippocampal CA1 neurons following transient global cerebral ischemia in the rat. Transient global cerebral ischemia was induced in male Wistar rats by four vessel- occlusion (4VO) for 10 min. Lipid peroxidation in brain tissues was determined by measuring the concentrations of thiobarbituric acid-reactive substances (TBARS). Furthermore, the apoptotic effects of ${H_2}{O_2}$ on PC12 cells were also investigated. Cell viabilities were measured using MTT [3-(4,5-dimethylthiazolyl-2)-2,-5-diphenyltetrazolium bromide] assays. Hydroxyfullerene, when administered to rats at 0.3-3 mg/kg i.p. at 0 and 90 minutes after 4-VO was found to significantly reduce CA1 neuron death by 72.4% on hippocampal CA1 neurons. Our findings suggest that hydroxyfullerene protects neurons from transient global cerebral injury in the rat hippocampus by reducing oxidative stress and lipid peroxidation levels, which contribute to apoptotic cell death.

• Archives of Reconstructive Microsurgery
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• v.9 no.1
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• pp.15-22
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• 2000

One hundred & seventy four consecutive free-flap transfers were reviewed to analyze distribution of the type of reconstructions, kinds of donor flaps as well incidence of complications. The role of emergent exploration and the effect of preoperative wound conditions in flap survival were evaluated. Free flap transfer for head and neck reconstruction was most common as 93 cases, followed by for upper extremity of 30 cases, for lower extremity 30 cases, 18 penile reconstructions and for trunk & breast 3 cases. Nine flaps exhibited signs of ciruclatory insufficiency between 5 hours and 7 days. Three were managed conservatively with ultimate partial necrosis of the flaps. Eight flaps required return to the operating room. On exploration, early arterial occlusion was revealed in 1 flap, late arterial occlusion in 2 flaps, early venous occlusion in 1 flap, late venous thrombosis in 2 flaps, prolonged venous spasm in 1 and hematoma in 1 flap. The average time from the first abnormal examination to exploration was 2.6 hours. There were no false-positive explorations. Four free flaps failed in spite of the correction of the cause of circulatory compromise. The remaining 4 flaps were salvaged following the correction the casuse. Recipient vessel problems such as irradiation and infection were the most common cause of circulatory crisis. Among the eight flaps requiring return to the operating room, single vein was anastomosed in three flaps and two veins in the remaining five. In the totally failed four flaps only single vein was anastomosed in three cases. The results of this study demonstrate the efficacy of clinical monitoring and the role of early exploration. Precautious selection of recipient vessels and two vein anastomosis are recommended for safe and better prognosis.

• The Korea Journal of Herbology
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• v.28 no.2
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• pp.1-7
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• 2013

Objectives : Sesamin, a major lignan in sesame seeds, has been reported to have neuroprotective effects against in vitro ischemia and in vivo MCAo-reperfusion cerebral ischemia model, however, there is no reports in an in vivo global cerebral ischemia model. The purpose of the study was to investigate the neuroprotective effect of sesamin in global cerebral ischemia induced by four-vessel occlusion (4-VO) in rats through inhibition of microglial activation in this model. Methods : The neuroprotective effects were investigated using a 10 min of 4-VO ischemia rat model by measuring intact pyramidal neurons in the CA1 region of the hippocampus using Nissle staining. The antiinflammatory or reducing neurotoxicity effect was investigated using immunohistochemisty, RT-PCR and western blot analysis of inflammatory or neurotoxic mediators. Results : Intraperitoneal injection of sesamin at doses of 0.3, 1.0, 3.0, and 10.0 mg/kg at 0 min and 90 min after ischemia conferred 26.6%, 30.1%, 42.5%, and 30.5% neuroprotection, respectively, compared to the vehicle-treated control group. A 3.0 mg/kg dose of sesamin inhibited microglia activation and consequently, cyclooxygenase-2, inducible nitric oxide, and interleukine-$1{\beta}$ expressions at 48 h after reperfusion. Conclusions : Sesamin protects neuronal cell death through inhibition of microglial activation or the production of neurotoxic metabolites and proinflammatory mediators by microglia such as COX-2, iNOS and IL-$1{\beta}$ in global cerebral ischemia.

• The Journal of Korean Medicine
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• v.23 no.4
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• pp.161-168
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• 2002

Objectives: Hwangryunhaedok-tang (Huang-lian-jie-du-tang, HRHDT, 黃連解毒湯) is a traditional Korean herbal medicine that is formulated with Coptidis Rhizoma, Phellodendri Cortex, Scutellariae Radix and Gardeniae Fructus. HRHDT is cold (寒) and bitter (苦) in nature and has general properties of clearing heat and detoxifying (淸熱解毒), strengthening the stomach and settling the liver (健胃平肝), and reducing inflammation, fever and swelling. This formula can prevent and treat artherosclerosis, hyperplasia of the endothelium, cerebral fluid circulation, cerebral vascular deterioration through aging, impairment of neurotransmitters, or disruption of the functioning of the cerebral cortex following infection or trauma. The purpose of the study reported here was to determine the neuroprotective effect of HRHDT on global ischemia induced by 4-vessel occlusion in Wistar rats. Methods: HRHDT extract was lyophilized after extraction with 85% methanol and 100% water. Rats were induced to 10 minutes of forebrain ischemia by 4-vessel occlusion (4-VO) and reperfused again. HRHDT was administered with a dose of 100 mg/kg, and 500 mg/kg of 85% methanol extracts and 100 mg/kg of 100% water extracts, respectively, at 0 min and 90 min after 4-VO. Rats were killed at 7 days after ischemia and the number of CA1 pyramidal neurons was counted in hippocampal sections stained with cresyl violet. Results: Body temperature of animals showed no significant difference between saline-treated groups and HRHDT extracts-treated groups until 5 hours of reperfusion. This result indicated that neuroprotective effects of HRHDT extracts were not due to hypothermic effects. The administration of HRHDT showed a significant neuroprotective effect on hippocampal CA1 neurons at 7 days after ischemia compared to the saline-treated group (P<0.001). HRHDT methanol extracts of 100 mg/kg, 500 mg/kg and HRHDT water extracts of 100 mg/kg showed 88.5%, 98.3% and 95.1 % neuroprotection, respectively. Conclusions: The results of this study demonstrate that administration of HRHDT is highly effective in reducing neuronal damage in response to transient global cerebral ischemia. HRHDT may involve many mechanisms that might account for its high degree of efficacy. A number of factors including free radicals, glutamate, calcium overload, NO, and various cytokines have been proposed to have an important role in causing neuronal death after short periods of global ischemia. Further studies are needed to know the neuroprotective mechanisms of HRHDT.

• Journal of Ginseng Research
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• v.31 no.1
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• pp.44-50
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• 2007

Ginseng powerfully tonifies the original Qi. Ginseng used for insomnia, palpitations with anxiety, restlessness from deficient Qi and blood and mental disorientation. In order to investigate whether Ginseng cerebral ischemia-induced neuronal and cognitive impairments, we examined the effect of Ginseng on ischemia-induced cell death in the hippocampus, and on the impaired learning and memory in the Morris water maze and passive avoidance in rats. Ginseng when administered to rat at a dose of 200 mg/kg i.p. water extracts to 0 minutes and 90 minutes after 4-VO, significantly neuroprotective effects by 86.4% in the hippocampus of treated rats. For behavior test, rats were administered Ginseng (200mg/kg p.o.) daily for two weeks, followed by their training to the tasks. Treatment with Ginseng produced a marked improvement in escape latency to find the platform in the Morris water maze. Ginseng reduced the ischemia-induced learning disability in the passive avoidance. Consistent with behavioral data, treatments with Ginseng reduced jschemia-induced cell death in the hippocampal CA1 area. Oxidative stress is a causal factor in the neuropathogenesis of ischemic-reperfusion injury. Oxidative stress was examined in a rat model of global brain ischemia. The effects of Ginseng on lipid peroxidation (inhibition of the production of malondialdehyde, MDA) in different regions of the rat brain were studied. Ferrous sulfate and ascorbic acid (FeAs) were used to induce lipid peroxidation. The antiperoxidative effect showed 48-72% protection from tissue damage as compared with untreated animals. These results showed that Ginseng have a protective effect against ischemia-induced neuronal loss and learning and memory damage.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.148.1-148.1
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• 2003

The effects of methanolic extracts of Polygalae Radix (PR 100mg/kg) was tested to evaluate on the neuroprotective activity (92％ p<0.001) on global cerebral schemia. Based on bioassays guided fractionation, butanol soluble fraction (BtOH 25mg/kg) had the neuroprotive effect (87％ p<0.001) of global cerebral ischemia in rat. Oxygen free radical injury plays an important role in neuronal damage induced by brain ischemia and reperfusion. (omitted)

• Journal of Chest Surgery
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• v.41 no.2
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• pp.160-169
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• 2008

Bakcground: To treat anastomosis site stenosis and occlusion of the artificial vessels used in vascular surgery, tissue-engineered artificial vessels using autologous cells have been constructed. We developed artificial vessels using a polymer scaffold and autologous bone marrow cells and performed an in vivo evaluation. Material and Method: We manufactured a vascular scaffold using biodegradable PLCL (poly lactide-co-${\varepsilon}$-caprolactone) and PGA (poly glycolic acid) fibers. Then we seeded autologous bone marrow cells onto the scaffold. After implantation of the artificial vessel into the abdominal aorta, we performed an angiography 3 weeks after surgery. After the dogs were euthanized we retrieved the artificial vessels and performed histological analysis. Result: Among the six dogs, 2 dogs died of massive bleeding due to a crack in the vascular scaffold 10 days after the operation. The remaining four dogs lived for 3 weeks after the operation. In these dogs. the angiography revealed no stenosis or occlusion at 3 weeks after the operation. Gross examination revealed small thrombi on the inner surface of the vessels and the histological analysis showed three layers of vessel structure similar to the native vessel. Immunohistochemical analysis demonstrated regeneration of the endothelial and smooth muscle cell layers. Conclusion: A tissue engineered vascular graft was manufactured using a polymer scaffold and autologous bone marrow cells that had a structure similar to that of the native artery. Further research is needed to determine how to accommodate the aortic pressure.

• The Korea Journal of Herbology
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• v.31 no.4
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• pp.101-109
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• 2016

Objectives : HT070 is a mixture of herbal extracts from root of Scutellaria baicalensis and stem bark of Eleutherococcus senticosus , which have long been used for stroke therapy in traditional Korean Medicine. The purpose of this study was to investigate the neuroprotective effects of HT070 on global cerebral ischemia and its potential mechanisms.Methods : Transient global cerebral ischemia was produced by 10 min of four-vessel occlusion (4-VO) in male Wistar rats. HT070 was administered orally at a dosage of 200 mg/kg twice at 0 and 90 min after reperfusion. Hippocampal neuronal damage was measured 7 days after reperfusion. To explore the potential mechanisms, we used hydrogen peroxide (H₂O₂)-induced rat pheochromocytoma (PC12) cells as an in vitro model. PC12 cells were pretreated with HT070 for 1 h and then exposed to 100 μM H₂O₂ for 6 h in the presence of HT070. Cell viability was measured by MTT assay and the mRNA expression of Bax, Bcl-2, iNOS and COX-2 were measured by quantitative RT-PCR.Results : Oral administration of HT070 at a dose of 200 mg/kg significantly reduced neuronal death in the hippocampal CA1 region by 13.4% as compared to the vehicle-treated group. HT070 increased cell viability, reversed the down-regulated Bcl-2 mRNA level, and suppressed the up-regulated mRNA expressions of Bax, iNOS, and COX-2 in H₂O₂-treated PC12 cells.Conclusions : HT070 protects against delayed neuronal death after global cerebral ischemia and its neuroprotection properties might be attributed to the inhibition of mitochondrial apoptosis and ROS-generating enzymes.

• Journal of Korean Neurosurgical Society
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• v.64 no.5
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• pp.693-704
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• 2021

Objective : Endovascular mechanical thrombectomy (MT) has been regarded as one of the standard treatments for acute ischemic stroke caused by large vessel occlusion. Despite the wide use of stent retrievers for MT, arterial intimal damage caused when deployed stent is pulled has been a certain disadvantage. We hypothesized that statin could protect and stabilize vessel damage after endovascular MT using a stent retriever. In this animal study, we observed the protective effects of the statins towards MT-induced vessel wall injury. Methods : Twenty-eight carotid arteries of fourteen rabbits were used in the experiments with MT using stent retriever. We divided the rabbits into four groups as follows : group 1, negative control; group 2, positive control; group 3, statin before MT; and group 4, statin after MT. After MT procedures, we harvested the carotid arteries and performed histomorphological and immunohistochemical analyses. Results : In histomorphological analysis with hematoxylin and eosin and Masson's trichrome stain, significant intimal thickening (p<0.05) was observed in the positive control (group 2), compared to in the negative control (group 1). Intimal thickening was improved in the statin-administered groups (groups 3 and 4 vs. group 2, p<0.05). We also observed that statin administration after MT (group 4) resulted in a more effective decrease in intimal thickness than statin administration before MT (group 3) (p<0.05). We performed immunohistochemical analysis with the antibodies for tumor necrosis factor-alpha (TNF-α), cluster of differentiation (CD)11b, and CD163. In contrast to the negative control (group 1), the stained percentage areas of all immunological markers were markedly increased in the positive control (group 2) (p<0.05). Based on statin administration, the percentage area of TNF-α staining was significantly reduced (p<0.05) in group 3, compared to the positive control group (group 2). However, significant differences were not observed for CD11b and CD163 staining. In group 4, no significant differences were observed for TNF-α, CD11b, and CD163 staining (p≥0.05). The differences in the percentage areas of the different markers between the statin-administered groups (groups 3 and 4) were also not revealed. Conclusion : We presented that statin administration before and after MT exerted protective effects towards vessel wall injury. The efficacy of statins was greater post-administration than pre-administration. Thus, statin administration in routine prescriptions in the peri-procedural period is strongly advised.

• Journal of Korean Neurosurgical Society
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• v.63 no.4
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• pp.427-432
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• 2020

Three randomized control trials (RCTs), published in 2013, investigated efficacy of mechanical thrombectomy in large vessel occlusions and did not show better results compared to intravenous (IV) recombinant tissue-type plasminogen activator (tPA) alone. However, most clinicians treating stroke consider mechanical thrombectomy as the standard treatment rather than using IV tPA alone. This paradigm shift was based on five RCTs investigating efficacy of mechanical thrombectomy in acute ischemic stroke conducted from 2010 to 2015. They demonstrated that mechanical thrombectomy was effective and safe in acute ischemic stroke with anterior circulation occlusion when performed within 6 hours of stroke onset. There are four reasons underlying the different results observed between the trials conducted in 2013 and 2015. First, the three RCTs of 2013 used low-efficiency thrombectomy devices. Second, the three RCTs used insufficient image selection criteria. Third, following the initial presentation at the hospital, reperfusion treatment required a long time. Fourth, the three RCTs showed a low rate of successful recanalization. Time is the most important factor in the treatment of acute ischemic stroke. However, current trends utilize advanced imaging techniques, such as diffusion-weighted imaging and multi-channel computer tomographic perfusion, to facilitate the detection of core infarction, penumbra, and collateral flows. These efforts demonstrate that patient selection may overcome the barriers of time in specific cases.