• 한방재활의학과학회지
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• 제21권2호
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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.

• 국제물리치료학회지
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• 제1권2호
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• pp.136-142
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• 2010

This study aims to reveal how EA affects BAX and NF-kB involved in cell deaths from global ischemia, and to do this, observes the changes of BAX and NF-kB caused by EA application after transient global ischemia. The experimental method is to give rise to global ischemia and apply EA to 27 SD rats with the particulars of being six-week-old, male, around-300 gram-weighing, and adapted to laboratory environment for more than a week, and divide them into three groups, that is, GV20 EA group(n=9), L14 EA group(n=9), no-treatment GI group(n=9), and then observe their changes of BAX and NF-kB at the time lapse of 6 hours, 9 hours and 12 hours after ischemia, using western blotting. The numerical decrease of BAX expression at the time lapse of 9 hours after EA application, though not statistically significant, was observed in GV20 EA group and L14 EA group, and the NF-kB expression appeared statistically significant decrease in GV20 EA group and L14 EA group, but the expression was higher in the group with EA application. Therefore, EA application at the early phase of global ischemia is considered to affect BAX and NF-kB and play a positive role in decreasing apoptosis and cell deaths by inflammation.

• 대한한의학회지
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• 제39권4호
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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.

• 한국전문물리치료학회지
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• 제17권1호
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• pp.69-76
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• 2010

Ischemia that causes stroke induces inflammation of brain cells and apoptosis and as a result, it influences much on the functional part of a man. The needle electrode electrical stimulation (NEES) that combines acupuncture of oriental medicine with electric therapy of western medicine relieves inflammation of cells and has effect on regrowth of nerve tissues. This study was conducted to verify the influence of NEES on the occurrence of c-Fos of cerebrum after applying NEES to the meridian point, Zusanli (ST 36) of a rats with induced ischemia. Global ischemia was induced by using ligation method on common carotid artery of male Sprague Dawley (SD) rats. The ligation was maintained for 5 minutes and then suture was removed for blood reperfusion. After inducing global ischemia, NEES was done to the left and right meridian points of Joksamri of a rat for 30 minutes after 12 hours, 24 hours, and 48 hours. The findings were as follows. 1. In the result of immunohistochemical method, the number of c-Fos immune response cells significantly decreased (P<.05) in NEES group than the control group (GI) that did not get NEES. 2. In the result of western blotting, the occurrence of c-Fos after 24 hours from the inducement of ischemia significantly decreased (P<.05) in NEES group than the control group (GI) that did not get NEES. Therefore, as the effect of NEES was shown highest after 24 hours from the ischemia, it is suspected that NEES would take important role in early treatment after cerebral stroke.

• 동의생리병리학회지
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• 제18권1호
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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.

• 대한한의학회지
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• 제27권4호
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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.

• 한국약용작물학회지
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• 제22권1호
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• pp.46-52
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• 2014

In traditional Korean and Chinese medicine, safflower (Carthamus tinctorius L.) for the treatment of central nervous system-related symptoms such as tremor, seizure, stroke and epilepsy. We investigated the effects of safflower could influence cerebral ischemia-induced neuronal and cognitive impairments. Administration of safflower for 1 day (200 mg/kg body weight, p.o.) increased the survival of hippocampal CA1 pyramidal neurons after transient global brain ischemia. And neurological functions measured as short term memory. Post-treatment with safflower for 2 times decreased the induction/reduction - induced production of neuronal cell loss from global cerebral ischemia. Safflower markedly decreased neuronal cell death and also caused a decrease in the content of thiobarbituric acid-reacting substances (TBARS) ($55.2{\pm}9.4{\mu}mol\;mg^{-1}$) and significant improvement of activities of glutathione (GSH) ($27.2{\pm}5.0{\mu}mol\;mg^{-1}$) in hippocampus. We conclude that treatment with safflower attenuated learning and memory deficits, and neuronal cell loss induced by global cerebral ischemia. These results suggest that safflower may be a potential candidate for the treatment of vascular dementia.

• The Korean Journal of Physiology and Pharmacology
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• 제2권3호
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• pp.279-286
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• 1998

It has been well documented that transient forebrain global ischemia causes selective neuronal degeneration in hippocampal CA1 pyramidal neurons with a delay of a few days. The mechanism of this delayed hippocampal CA1 pyramidal neuronal death (DND) is still controversial. To delineate the mechanisms of the DND, the effects of treatment with MK-801, an NMDA receptor antagonist, kynurenic acid, a NMDA/non-NMDA receptor antagonist, and/or cycloheximide, a protein synthesis inhibitor, on the DND were investigated in male Wistar rats. To examine the participation of apoptotic neuronal death in the DND, TUNEL staining was performed in ischemic brain section. Global ischemia was induced by 4-vessel occlusion for 20 min. All animals in this study showed the DND 3 and 7 days after the ischemic insult. The DND that occured 3 days and 7 days after the ischemia were not affected by pretreatment with MK-801 (1 mg/kg), but markedly attenuated by the pretreatment with kynurenic acid (500 mg/kg). Treatment with cycloheximide (1 mg/kg) also markedly inhibited the DND. The magnitudes of attenuation by the two drugs were similar. The magnitude of attenuation by co-treatments with kynurenic acid and cycloheximide was not greater than that with any single treatment. TUNEL staining was negative in the sections obtained 1 or 2 days after the ischemic insults, but it was positive at hippocampal CA1 pyramidal cells in sections collected 3 days after the ischemia. These results suggested that the DND should be mediated by the activation of non-NMDA receptor, not by the activation of NMDA receptor and that the activation of AMPA receptor should induce the apoptotic process in the DND.

• The Korean Journal of Physiology and Pharmacology
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• 제24권1호
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• pp.11-18
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• 2020

The present study was aimed to explore the neuroprotective role of imatinib in global ischemia-reperfusion-induced cerebral injury along with possible mechanisms. Global ischemia was induced in mice by bilateral carotid artery occlusion for 20 min, which was followed by reperfusion for 24 h by restoring the blood flow to the brain. The extent of cerebral injury was assessed after 24 h of global ischemia by measuring the locomotor activity (actophotometer test), motor coordination (inclined beam walking test), neurological severity score, learning and memory (object recognition test) and cerebral infarction (triphenyl tetrazolium chloride stain). Ischemia-reperfusion injury produced significant cerebral infarction, impaired the behavioral parameters and decreased the expression of connexin 43 and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in the brain. A single dose administration of imatinib (20 and 40 mg/kg) attenuated ischemia-reperfusion-induced behavioral deficits and the extent of cerebral infarction along with the restoration of connexin 43 and p-STAT3 levels. However, administration of AG490, a selective Janus-activated kinase 2 (JAK2)/STAT3 inhibitor, abolished the neuroprotective actions of imatinib and decreased the expression of connexin 43 and p-STAT3. It is concluded that imatinib has the potential of attenuating global ischemia-reperfusion-induced cerebral injury, which may be possibly attributed to activation of JAK2/STAT3 signaling pathway along with the increase in the expression of connexin 43.

• Journal of Yeungnam Medical Science
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• 제12권2호
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• pp.260-268
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• 1995

건전한 뇌의 수분 함량은 뇌혈류장벽의 투과성, 혈관내 정수압, 혈장의 삼투압 Na-K-APTase pump의 기능에 의해서 결정된다. 뇌허혈에 의해 이러한 기전이 파괴되면 세포 사이의 정상적인 수분이동이 영향을 받게 된다. 그러므로 뇌허혈이 생길 수 있는 수술의 경우에 분리 뇌관류를 하면 뇌허혈시 발생하는 독성 대사물을 발생을 억제하고 뇌혈류의 분포를 개선하여 신경세포의 손상을 줄이고 뇌부종을 감소시킬 수 있으리라 생각되어 토끼에서 분리 뇌관류 모델을 만들어 허혈 유도 후 관류군과 비관류군의 대뇌피질과 해면구의 비중을 정상 토끼와 비교하였다. 뇌허혈에 의해 관류군과 비관류군의 뇌비중이 유의하게 감소하여 뇌부종이 발생하였음을 나타내었고, 비관류군이 판류군보다 유의하게 감소하여 뇌부종이 더욱 현저하였던 것으로 보아 냉각 식염수로 뇌관류한 것이 뇌부종의 발생을 억제한 것으로 생각된다.