• 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.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.2
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• pp.1-13
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• 2011

Objectives : We investigated the effect of Haein-tang(Hairen-tang) on short-term memory and apoptosis in dentate gyrus of the gerbils with transient global ischemia. Methods : For the induction of cerebral ischemia model in mice, common carotid arteries of gerbils were occluded with aneurysm clips for 5 min. One day after operation, Haein-tang(Hairen-tang) was administrated orally injected once a day for 15 consecutive days. Gerbils were randomly divided into four group(n=10 in each group): sham-operation group, ischemia-induction group, ischemia-induction and 50 mg/kg Haein-tang(Hairen-tang)-treated group, ischemia-induction and 100 mg/kg Haein-tang(Hairen-tang)-treated group, and ischemia-induction and 200 mg/kg Haein-tang(Hairen-tang)-treated group. The effect of Haein-tang(Hairen-tang) on memory function was investigated by using step-down avoidance task. Apoptosis was confirmed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) staining and immunohistochemistry for caspase-3. Western blot analysis for the expressions of Bax and Bcl-2 protein was also conducted. Results : 1. Haein-tang extract significantly enhanced short-term memory in step-down avoidance task and 100 mg/kg, 200 mg/kg Haein-tang-treated group. 2. Haein-tang extract significantly suppressed TUNEL-positive cells after transient global ischemia and 50 mg/kg, 100 mg/kg, 200 mg/kg Haein-tang-treated group. 3. Haein-tang extract significantly increased caspase-3 positive cells in the hippocampal dentate gyrus after transient global ischemia and 50 mg/kg, 100 mg/kg, 200 mg/kg Haein-tang-treated group. 4. Haein-tang extract significantly decreased Bax protein expressions in the hippocampus after transient global ischemia and 100 mg/kg, 200 mg/kg, Haein-tang-treated group. Haein-tang extract significantly increased Bcl-2 protein expressions in the hippocampal dentate gyrus after transient global ischemia and 50 mg/kg, 100 mg/kg, 200 mg/kg, Haein-tang-treated group. Haein-tang extract significantly decreased Ratio of Bax protein to Bcl-2 protein in the hippocampus after transient global ischemia and 100 mg/kg, 200 mg/kg Haein-tang-treated group. Conclusions : While Haein-tang(Hairen-tang) treatment improved short-term memory by suppressing on ischemia-induction apoptosis. In the present study, Haein-tang(Hairen-tang) shows protective effect on transient global ischemia.

• The Journal of Korean Medicine
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• v.26 no.3 s.63
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• pp.146-161
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• 2005

Objectives : This study investigated neuroprotective effects of Polygoni Multiflori Radix on cerebral ischemia of hyperlipidemic rats. Methods : Effects of Polygoni Multiflori Radix were evaluated with changes of infarct size after He focal cerebral ischemia induced by the middle cerebral artery occlusion, changes of pyramidal neurons and expressions of Bax and Bcl-2 apoptosis regulating factors after global cerebral ischemia, and changes of serum lipid revels after cerebral ischemia. Results & Conclusions : Results obtained were as follows; 1. Polygoni Multiflori Radix did net reduce the focal cerebral infarct size induced by the middle cerebral artery occlusion under both hyperlipidemic and normal-lipid conditions. 2. Polygoni Multiflori Radix significantly reduced the increase of neuronal cell death in CAl region of hippocampus induced by the global cerebral ischemia under both hyperlipidemic and normal-lipid conditions. 3. Polygoni Multiflori Radix significantly reduced the increase of Bax expression in the CAl region of the hippocampus induced by global cerebral ischemia under both hyperlipidemic and normal-lipid conditions. 4. Polygoni Multiflori Radix significantly increased Bc1-2 expression in the CA1 region of the hippocampus after global cerebral ischemia under normal-lipid condition, but was not effective on that under hyperlipidemic condition. 5. Polygoni Multiflori Radix was not effective on serum total-cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride levels under normal-lipid conditions, irrespective of focal cerebral infarct or global cerebral ischemia. 6. Polygoni Multiflori Radix significantly reduced the increase of serum total-cholesterol and triglyceride levels, and increased serum LDL-cholesterol level under hyperlipidemic conditions, irrespective of foc31 cerebral infarct or global cerebral ischemia.

• The Journal of Dong Guk Oriental Medicine
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• v.7 no.2
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• pp.149-154
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• 1999

The effect of Yukilsunki-tang extracts on global cerebral ischemia were investigated in this study. The multiple parameters of global cerebral ischemia assessed in mice included the duration of KCN-induced(1.8mg/kg i.v.) coma, the survival time of KCN-induced(3.0mg/kg i.v.) coma, the survival time exposed to hypoxia induced by vacuum pump. In the case of global cerebral ischemia International Cancer Research mice were used and divided into two groups at random Group A, normal control, was treated after oral administration of normal saline. Group B, experimental control, was treated after oral administration of 13.2mg/20g of Yukilsunki-tang extracts. Each treatment was KCN-induced(1.8mg/kg i.v.) coma, KCN-induced(3.0mg/kg i.v.) coma and exposure to hypoxia induced by vacuum pump. The results were obtained as follows ; In global cerebral ischemia, Yukilsunki-tang extracts significantly prolonged the duration of KCN-induced(1.8mg/kg i.v.) coma, the survival time of KCN-induced(3.0mg/kg i.v.) coma and the survival time of exposure to hypoxia induced by vacuum pump in mice. Conclusion Yukisunki-tang extracts had a significant effect on Global cerebral ischemia.

• The Korea Journal of Herbology
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• v.27 no.6
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• pp.83-90
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• 2012

Objectives : Modified Bo-Yang-Hwan-O-Tang (mBHT) is a polyherbal medicine of twelve herbs traditionally used in the treatment of cerebral and cardiac stroke and vascular dementia. The purpose of this study was to evaluate the neuroprotective effect, pyramidal neuronal cell, inflammation and apoptosis of mBHT against global ischemia in rats. Methods : Global ischemia was produced by two-vessel occlusion(2-VO) in SD male rats. mBHT at dose of 500 mg/kg was orally administrated for 2 weeks or 6 weeks after global ischemia. The histopathological changes of ischemic brain were observed by staining of hematoxylin and eosin (H&E) and Nissl and immunohistochemisty with anti-GFAP (glial fibrillary acidic protein) antibody as a astrocyte marker. The expression of inducible nitric oxide synthase (iNOS) and apoptotic proteins such as Bax, Bcl-2 and caspase-3 was determined by western blot. Results : mBHT treatment significantly inhibited the pyramidal neuronal loss in CA1 of hippocampus of global ischemic rats by 2-VO. mBHT also suppressed the activation of astrocytes in the CA1 at 6 weeks after ischemia. In addition, mBHT significantly increased the expression of anti-apoptotic protein, Bcl-2 on iscemic brain, and significantly attenuated the expression of apoptotic proteins, Bax and caspase-3. Conclusions : These results indicate that mBHT inhibits neuronal cell damage induced in global ischemia by 2-VO, suggesting that mBHT may be a potential candidate for the treatment of vascular dementia.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.1
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• pp.73-79
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• 2000

This study investigated whether propofol, an intravenous, non-barbiturate anesthetic, could reduce brain damage following global forebrain ischemia. Transient global ischemia was induced in gerbils by occlusion of bilateral carotid arteries for 3 min. Propofol (50 mg/kg) was administered intraperitoneally 30 min before, immediately after, and at 1 h, 2 h, 6 h after occlusion. Thereafter, propofol was administered twice daily for three days. Treated animals were processed in parallel with ischemic animals receiving 10% intralipid as a vehicle or with sham-operated controls. In histologic findings, counts of viable neurons were made in the pyramidal cell layer of the hippocampal CA1 area 4 days after ischemia. The number of viable neurons in the pyramidal cell layer of CA1 area was similar in animals treated with a vehicle or a subanesthetic dose of propofol. In terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) assay, semiquantitative analysis of dark-brown neuronal cells was made in the hippocampal CA1 area. There was no significant difference in the degree of TUNEL staining in the hippocampal CA1 area between vehicle-treated and propofol-treated animals. These results show that subanesthetic dose of propofol does not reduce delayed neuronal cell death following transient global ischemia in Mongolian gerbils.

• Journal of International Academy of Physical Therapy Research
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• v.3 no.2
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• pp.429-434
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• 2012

Ischemia, the leading cause of strokes, is known to be deeply related to synaptic plasticity and apoptosis in tissue damage due to ischemic conditions or trauma. The purpose of this study was to research the effects of NEES(needle electrode electrical stimulation) in brain cells of ischemia-induced rat, more specifically the effects of Poly[ADP-ribose] polymerase(PARP) on the corpus striatum. Ischemia was induced in SD mice by occluding the common carotid artery for 5 minutes, after which blood was re-perfused. NEES was applied to acupuncture points, at 12, 24, and 48 hours post-ischemia on the joksamri, and at 24 hours post-ischemia on the hapgok. Protein expression was investigated through PARP antibody immuno-reactive cells in the cerebral nerve cells and western blotting. The number of PARP reactive cells in the corpus striatum 24 hours post-ischemia was significantly(p<.05) smaller in the NEES group compared to the global ischemia(GI) group. PARP expression 24 hours post-ischemia was very significantly smaller in the NEES group compared to the GI group. Results show that ischemia increases PARP expression and stimulates necrosis, making it a leading cause of death of nerve cells. NEES can decrease protein expression related to cell death, protecting neurons and preventing neuronal apoptosis.

• The Journal of the Korea institute of electronic communication sciences
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• v.8 no.12
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• pp.1949-1958
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• 2013

This study conducted observation of tissues using the immunohistochemistry methods in order to see the effect of Needle Electrode Electrical Stimulation(: NEES) on apoptosis in the SD rat cerebellum caused by global ischemia which came from common carotid artery occlusion. The comparison and analysis results of expression of factors related to apoptosis among the control group, the global ischemia group and the NEES group showed that NEES following global ischemia had a significant effect on the reduction of c-fos expression in the SD rat cerebellum, and didn't have a significant effect on the reduction of bax and caspase-3 expression. In conclusion, it is considered that NEES following global ischemia is partially effective in suppressing the expression of factors related to apoptosis.

• 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.

• Journal of International Academy of Physical Therapy Research
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• v.7 no.2
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• pp.1031-1036
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• 2016

c-Fos is known to related to synaptic plasticity and apoptosis in damage from ischemia or external injury. The purpose of this study was to investigate whether needle electrode electrical stimulation(NEES) is effective in increasing the number of c-Fos response cells and c-Fos expression in striatum after global ischemia in rats. There were no treatment and occlusion in the control group, global ischemia(GI) group were no treatment after carotid artery occlusion, and needle electrode electrical stimulation(NEES) group were treated with NEES after GI induced. The number of striatum c-Fos response cells and c-Fos protein expression significantly decreased in the NEES group compared to the GI group after 12, 24, 48 hours. The results of the present study suggest that NEES is ineffective in improving global ischemia in rats and may also be ineffective in the globally ischemic human brain.