• 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 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.

• The Journal of Korean Medicine
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• v.39 no.4
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• pp.1-15
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• 2018

Objectives: Cerebral ischemia results from a variety of causes that cerebral blood flow is reduced due to a transient or permanent occlusion of cerebral arteries. Reactive astrocytes and microglial activation plays an important role in the neuronal cell death during ischemic insult. Acupunctural treatment is effective for symptom improvement in cerebrovascular accident, including cerebral ischemia. Methods: In the present study, the effects of acupuncture at the ST40 acupoint on short-term memory and apoptosis in the hippocampal CA1 region following transient global cerebral ischemia were investigated using gerbils. Transient global ischemia was induced by occlusion of both common carotid arteries with aneurysm clips for 5 min. Acupuncture stimulation was conducted once daily for 7 consecutive days, starting one day after surgery. Results: In the present results, ischemia induction deteriorated short term memory, increased apoptosis, and induced reactive astrocyte and microglial activation. Acupuncture at ST40 acupoint ameliorated ischemia-induced short-term memory impairment by suppressing apoptosis in the hippocampus through down-regulation of reactive astrocytes and microglial activation. Conclusion: The present study suggests that acupuncture at the ST40 acupoint can be used for treatment of patients with cerebral stroke.

• 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 Physiology & Pathology in Korean Medicine
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• v.18 no.1
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• pp.236-242
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• 2004

Cerebral ischemia resulting from transient or permanent occlusion of cerebral arteries leads to neuronal cell death and eventually causes neurological impairments. Bee venom has been used for the treatment inflammatory disease. In the present study, the effects of bee venom on apoptosis and cell proliferation in the hippocampal dentate gyrus following transient global ischemia in gerbils were investigated using immunohistochemistry for cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), caspase-3, and 5-bromo-2'-deoxyuridine (BrdU). It was shown that apoptotic cell death and cell proliferation in the hippocampal dentate gyrus were significantly increased following transient global ischemia in gerbils and that treatment of bee venom suppressed the ischemia-induced increase in apoptosis and cell proliferation in the dentate gyrus. The present results also showed that 1 mg/kg bee-venom treatment suppressed the ischemia-induced increasing apoptosis, cell proliferation, and COX-2 expression in the dentate gyrus. It is possible that the suppression of cell proliferation is due to the reduction of apoptotic cell death by treatment of bee venom. In the present study, bee venom was shown to prosses anti-apoptotic effect in ischemic brain disease, and this protective effect of bee venom against ischemia-induced neuronal cell death is closely associated with suppression on caspase-3 expression.

• The Journal of Korean Medicine
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• v.27 no.4
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• pp.105-115
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• 2006

Fucoidan has been shown to exhibit a host of biological activities, including anti-coagulant, anti-thrombotic, anti-tumourigenic, anti-inflammatory, anti-viral, anti-complementary and neuroprotective effects. In the present study, we attempted to determine the effects of Fucoidan on both apoptosis and cell proliferation in the hippocampal CA1 region and the dentate gyrus of gerbils after the induction of transient global ischemia. This experiment involved the use of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay as well as immunohistochemisty for caspase-3 and 5-bromo-2'-deoxyuridine (BrdU). The monosaccharide composition of the purified Fucoidan which had been extracted from Laminaria religiosa was utilized in this study. The present study clearly induces that apoptotic cell death and cell proliferation in the gerbil's hippocampal regions increased significantly following the induction of transient global ischemia and the results of this study also indicate that Fucoidan exerted a suppressive effect on this observed ischemia-induced increase in apoptosis within the CA1 and dentate gyrus, and also suppressed cell proliferation in the dentate gyrus.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.2
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• pp.15-30
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• 2011

Objectives : The present study investigated the effects of Achyranthis Radix on short-term memory, apoptotic neuronal cell death in the hippocampus following transient global ischemia in gerbils. Methods : The gerbils were divided into 5 groups(n=10); Sham operation group, ischemia-induced group, ischemia-induced and 50 mg/kg Achyranthis Radix-treated group, ischemia-induced and 100 mg/kg Achyranthis Radix-treated group, ischemia-induced and 200 mg/kg Achyranthis Radix-treated group. For this study, a step-down avoidance task, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) assay, immunohistochemistry for caspase-3 and BrdU(5-Bromo-2'-deoxyuridine), and western blotting for bax, bcl-2 were performed. Results : The results revealed that ischemic injury impaired short-term memory and increased apoototic neuronal cell death in the hippocampal CA1(cornu ammonis area 1) region. Ischemic injury enhanced cell proliferation in the hippocampal CA1 region, the compensatory and adaptive process for excessive apoptosis. Achyranthis Radix treatment improved short-term memory by suppressing ischemia-induced apoptotic neuronal cell death in the hippocampal CA1 region. Also, Achyranthis Radix suppressed the ischemia-induced increase in cell proliferation in the hippocampal CA1 region. Conclusions : We showed that Achyranthis Radix alleviates ischemia-induced apoptotic neuronal cell death, thus facilitates the recovery of short-term memory impairment induced by ischemic cerebral injury.

• Journal of Yeungnam Medical Science
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• v.12 no.2
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• pp.260-268
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• 1995

Ischemia results when the decrease in tissue perfusion exceeds the tissues ability to increase an oxygen extraction from the blood. Brain edema has been defined as an abnormal accumulation of fluid within brain parenchyma associated with a volumetric enlargement of the brain tissue. In most instances, the labelling of edema as vasogenic or cytotoxic is only relative. For cerebral protection, there were many possible techniques which could increase or maintain cerebral perfusion and reduce cerebral metabolic demand for oxygen. This study was carried out the effect of mild brain hypothermia which was induced by infusion with cold saline into the carotid artery, during brief episodes of transient global ischemia on postischemic brain edema in rabbit. Eight rabbits were anesthetized with halothane and mechanically ventilated with oxygen. For isolated cerebral perfusion, polyethylene catheter was inserted left carotid artery for infusion of cold saline, external carotid artery was ligated, vertebral arteries were cautherized, right carotid artery was snared for ischemia and femoral artery and vein were also canulated for monitoring and drug treatment. At 3 hours After transient global ischemia, specific gravity of cerebral cortex and hippocampus was compared with no-perfusion group , perfusion with cold saline group and normal group. There was no significant differences in physiologic variables among the groups before transient global ischemia. But during transient global ischemia, brain temperature of perfusion group was decreased when compared to no perfusion group. Specific gravity of cerebral cortex and hippocampus of no-perfusion group and perfusion group was statistically significant when compared to normal group (p<0.01). The results of this study suggested that mild brain hypothermia with intracarotid cold saline infusion during brief episodes of transient global ischemia had decreased postischemic brain edema in rabbit.

• Molecular Medicine Reports
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• v.21 no.1
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• pp.107-114
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• 2020

Nuclear receptor related 1 protein (Nurr1), a member of the nuclear receptor 4 family of orphan nuclear receptors, has been reported to display anti-inflammatory properties. The present study investigated the alteration of Nurr1 immunoreactivity in the gerbil hippocampus proper following 5 min of transient global cerebral ischemia. In sham operated gerbils, Nurr1 immunoreactivity was observed in pyramidal neurons in all cornu ammonis 1-3 (CA1-3) subfields of the hippocampus proper. In ischemia-operated gerbils, Nurr1 immunoreactivity was altered in the CA1 subfield. Nurr1 immunoreactivity in CA1 pyramidal neurons gradually decreased until 2 days post-ischemia, and, at 4 days post-ischemia, Nurr1 immunoreactivity was concentrated in CA1 pyramidal neurons. Additionally, Nurr1 immunoreactivity was newly expressed in microglia in the CA1 subfield at 4 days post-ischemia. Conversely, in the CA2/3 subfield, time-dependent alteration of Nurr1 immunoreactivity was not identified at any time following ischemia. These results indicated that the alteration of Nurr1 expression in the CA1 subfield in the hippocampus may be associated with the death of CA1 pyramidal neurons.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.205.1-205.1
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• 2003

Several lines of recent evidences have shown that several pro-inflammatory genes or mediators, such as inducible nitric oxide synthase (iNOS)are strongly expressed in the ischemic brain. Inflammation is now recognized as a significant contributing mechanism in cerebral ischemia because anti-inflammatory compounds or inhibitors of iNOS have been proven to reduce ischemic brain damage. In iNOS assay, hexane fraction of M61 inhibited NO (iNOS IC50, 0.7${\mu}$g/ml). In vivo study was carried out to evaluate neuroprotective effect of hexane fraction of M61 after transient global ischemia using Mongolian gerbil ischemia model. (omitted)