• Journal of Korean Neurosurgical Society
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• 제49권1호
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• pp.1-7
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• 2011

Objective: Glutamate is a key excitatory neurotransmitter in the brain, and its excessive release plays a key role in the development of neuronal injury. In order to define the effect of nimodipine on glutamate release, we monitored extracellular glutamate release in real-time in a global ischemia rat model with eleven vessel occlusion. Methods: Twelve rats were randomly divided into two groups: the ischemia group and the nimodipine treatment group. The changes of extracellular glutamate level were measured using microdialysis amperometric biosensor, in coincident with cerebral blood flow (CBF) and electroencephalogram. Nimodipine (0.025 ${\mu}g$/100 gm/min) was infused into lateral to the CBF probe, during the ischemic period. Also, we performed Nissl staining method to assess the neuroprotective effect of nimodipine. Results: During the ischemic period, the mean maximum change in glutamate concentration was $133.22{\pm}2.57\;{\mu}M$ in the ischemia group and $75.42{\pm}4.22\;{\mu}M$ (p<0.001) in the group treated with nimodipine. The total amount of glutamate released was significantly different (P<0.001) between groups during the ischemic period. The %cell viability in hippocampus was $47.50{\pm}5.64$ (p<0.005) in ischemia group, compared with sham group. But, the %cell viability in nimodipine treatment group was $95.46{\pm}6.60$ in hippocampus (p<0.005). Conclusion: From the real-time monitoring and Nissl staining results, we suggest that the nimodipine treatment is responsible for the protection of the neuronal cell death through the suppression of extracellular glutamate release in the 11-VO global ischemia model of rat.

• Journal of Korean Neurosurgical Society
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• 제43권3호
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• pp.131-134
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• 2008

Objective: The surgical approach for anterior choroidal artery (AChA) aneurysm is typically similar to those used for other supraclinoid internal carotid artery (ICA) lesions. However, the surgical clipping of this aneurysm is complicated and as a result. can result in postoperative ischemic complications. The purpose of this study was to clarify the risk of clip-induced ischemic complication in AChA aneurysm and to get the benefits for helping decision making. Methods: We retrospectively investigated 53 cases (4.0%) of AchA aneurysm treated surgically. We divided the AChA aneurysm to 3 subtype according to the origin of aneurysmal neck; A type originating from the AChA itself. J type from junction of AChA and ICA and I type from the ICA itself. We evaluated brain CT about 1 week post-operative day to confirm the low density in AChA territory. Results: Ruptured aneurysm was 26 cases and unruptured aneurysm 27 cases. The aneurysmal subtype of A, J, and I was 13, 17, and 23 cases. Of the 53 cases who performed surgical neck clipping, twelve (22.6%) had postoperative AChA distribution infarcts. Increased infarct after neck clipping had statistic significance in non-I subtype (r=0.005) Conclusion: AChA aneurysm surgery carries a significant risk of postoperative stroke. Don't always stick to clipping only, especially in non-I type of incidental small aneurysm, which has high risk of post-clip ischemic complications.

• 동의생리병리학회지
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• 제16권3호
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• pp.594-601
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• 2002

The current study was carried out to evaluate neuroprotective effects of Citri Pericarpium after transient global ischemia in gerbils. Male Mongolian gerbils weighing 60-80g were anesthetized with 2% isoflurane mixed with 30% oxygen and 70 % nitrogen. Bilateral common carotid arteries were occluded for 5 minute with microaneurysm dips. On 3 or 7 days after ischemic surgery, the gerbils were sacrificed. The brain were removed, embedded in paraffin and sectioned at 8㎛-thickness. Gerbils that received ischemic insult for 5 min showed extensive neuronal damage in the hippocampal CA1 region, and the number of viable neuronal cell was 51.0±2.5/mm, 32.2% of normal group at 7 days after ischemic surgery. In animals that underwent the extract of Citri Pericarpium treatment, the number of viable neuronal cell were significantly better preserved at 110.58±3.58/mm, 72.0% of normal group than those of ischemic group (P<0.01). In the immunohistochemistry of Bax and Bcl-2, the Citri Pericarpium treated group down-regulated the expression of Bax protein at 72hr after transient global ischemia. In contrast, Bcl-2 protein level was not changed. The appearance in TUNEL assay is similar to the pattern of Bax protein. The water extract of Citri Pericarpium significantly reduced the number of TUNEL-positive CA1 pyramidal neurons at 72hr. The results suggest that Citri Pericarpium has potential neuroprotective effects in the transient global ischemia and the increase in the ratio of Bcl-2 to Bax may contribute to the anti-apoptotic effect of Citri Pericarpium.

• 동의생리병리학회지
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• 제25권4호
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• pp.734-742
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• 2011

The purpose of this study was to investigate the distribution and correlation of stroke risk factor according to age with stroke patients. This study was based on clinical data registered in Daejeon Oriental Medical Hospital from November 2006 to December 2010. Study subjects consisted of 779 patients with stroke within 1 month and they were classified according to age and existence of past history such as hypertension, diabetes mellitus, ischemic heart diseaseand stroke family history. Stroke family history was distributed differently according to age unlike past history and in their 50's showed a particularly high rate. There was not statistically significant correlation between stroke family history and past history except for only between stroke family history and diabetes mellitus in the patients in their 80's and more. There was statistically significant correlation between hypertension and diabetes mellitus and especially in the patients in their 60's and 70's. There was statistically significant correlation between hypertension and ischemic heart disease and especially in the patients in their 80's and more. There was statistically significant correlation between diabetes mellitus and ischemic heart disease in the patients in their 60's. There was statistically significant correlation among hypertension, diabetes mellitus and ischemic heart disease, but stroke family history and past history had independence, so management and research for this subject should be required further and further.

• Journal of Preventive Medicine and Public Health
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• 제40권2호
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• pp.130-136
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• 2007

Objectives : Recent educational efforts have concentrated on patient's early hospital arrival after symptom onset. The purpose of this study was to evaluate the time interval between symptom onset and hospital arrival and to investigate its relation with clinical outcomes for patients with acute ischemic stroke. Methods : A prospective registry of patients with signs or symptoms of acute ischemic stroke, admitted to the OO Medical Center through emergency room, was established from September 2003 to December 2004. The interval between symptom onset and hospital arrival was recorded for each eligible patient and analyzed together with clinical characteristics, medication type, severity of neurologic deficits, and functional outcomes. Results : Based on the data of 256 patients, the median interval between symptom onset and hospital arrival was 13 hours, and 22% of patients were admitted to the hospital within 3 hours after symptom onset. Patients of not-mild initial severity and functional status showed significant differences between arrival hours of 0-3 and later than 3 in terms of their functional outcomes on discharge. Logistic regression models also showed that arrival within 3 hours was a significant factor influencing functional outcome (OR=5.6; 95% CI=2.1, 15.0), in addition to patient's initial severity, old age, cardioembolism subtype, and referral to another hospital. Conclusions : The time interval between symptom onset and hospital arrival significantly influenced treatment outcome for patients with acute ischemic stroke, even after controlling for other significant clinical characteristics. The findings provided initiatives for early hospital arrival of patients and improvement of emergency medical system.

• Molecules and Cells
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• 제45권4호
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• pp.216-230
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• 2022

SERTA domain-containing protein 1 (Sertad1) is upregulated in the models of DNA damage and Alzheimer's disease, contributing to neuronal death. However, the role and mechanism of Sertad1 in ischemic/hypoxic neurological injury remain unclear. In the present study, our results showed that the expression of Sertad1 was upregulated in a mouse middle cerebral artery occlusion and reperfusion model and in HT22 cells after oxygen-glucose deprivation/reoxygenation (OGD/R). Sertad1 knockdown significantly ameliorated ischemia-induced brain infarct volume, neurological deficits and neuronal apoptosis. In addition, it significantly ameliorated the OGD/R-induced inhibition of cell viability and apoptotic cell death in HT22 cells. Sertad1 knockdown significantly inhibited the ischemic/hypoxic-induced expression of p-Rb, B-Myb, and Bim in vivo and in vitro. However, Sertad1 overexpression significantly exacerbated the OGD/R-induced inhibition of cell viability and apoptotic cell death and p-Rb, B-Myb, and Bim expression in HT22 cells. In further studies, we demonstrated that Sertad1 directly binds to CDK4 and the CDK4 inhibitor ON123300 restores the effects of Sertad1 overexpression on OGD/R-induced apoptotic cell death and p-Rb, B-Myb, and Bim expression in HT22 cells. These results suggested that Sertad1 contributed to ischemic/hypoxic neurological injury by activating the CDK4/p-Rb pathway.

• 동의신경정신과학회지
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• 제22권4호
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• pp.201-218
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• 2011

Objectives : The aim of this study was to investigate the effects of Guibi-Tang(GBT) on focal brain ischemic injury induced by intraluminal filament insertion in rats. Methods : The ischemia was induced by intraluminal filament insertion into middle cerebral artery. Sprague-Dawley rats were divided into five groups, normal group(n=8); control group was ischemia induced and no treatment(n=8); GBT 1X group was ischemia induced and administrated 42.2 mg/ml/kg of Guibi-Tang orally(n=8); GBT 3X group was ischemia induced and administrated 126.6 mg/ml/kg of Guibi-Tang orally(n=8); GBT 6X group was ischemia induced and administrated 253.2 mg/ml/kg of Guibi-Tang orally(n=8) for 21 days. mGluR5, Bax, Bcl-2 and cytochrome C were investigated to observe the effects of Guibi-Tang on apoptosis. The effects of Guibi-Tang on neuroprotective/apoptotic agents in cresyl violet, choline acetyltranferase(ChAT) with ischemic injury were investigated. Results : The intensity of mGluR5 mRNA in the hippocampal CA1 was increased in normal and GBT(Guibi-Tang) 1X groups compared with the control group. The intensity of Bax mRNA in the hippocampal CA1 was decreased in normal and GBT 1X groups compared with the control group. However it was increased unexpectedly in GBT 3X group. The intensity of Bcl-2 mRNA in the hippocampal CA1 was increased in normal and GBT 1X groups compared with the control group. The intensity of Bax/Bcl-2 ratio in the hippocampal CA1 was decreased in normal and GBT 1X groups compared with the control group. The intensity of cytochrome C protein in the hippocampal CA1 was decreased in normal, GBT 1X and GBT 6X groups compared with the control group. The density of neurons stained by cresyl violet and ChAT was increased in normal and GBT 1X groups compared with the control group. Conclusions : These results suggest that Guibi-Tang may have protective effect on vascular dementia.

• Biomolecules & Therapeutics
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• 제29권3호
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• pp.321-330
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• 2021

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H2O2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

• 대한임상검사과학회지
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• 제54권4호
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• pp.256-264
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• 2022

허혈성 뇌졸중은 뇌동맥의 혈전이나 색전에 의해 폐색되어 산소가 포함된 혈액이 뇌에 도달하는 것을 방지하고, 신경 세포의 괴사를 유발하는 것이다. 본 연구의 목적은 지금까지 연구된 허혈성 뇌졸중의 조기 진단을 가능하게 하는 심혈관 질환 및 심방세동 질환과 관련된 혈청 후보 마커를 정리하고, 각 마커의 OR을 비교 분석하는 것이다. 본 연구에서는 메타분석 기법을 이용하여 혈청 후보 마커의 효과 크기를 분석하고자 하였다. '심혈관질환', '심방세동', '허혈성 뇌졸중', '혈청 표지자'를 키워드로 포함하는 논문에 대한 학술 Database 검색에서 추출된 데이터는 모두 허혈성 뇌졸중 환자에 대한 결과로 제한하였다. 이 연구에서 가장 많이 검색된 마커는 NT-proBNP, D-dimer, CRP 및 GFAP 등으로 나타났다. 결론적으로, NT-proBNP는 허혈성 뇌졸중의 조기 진단에 매우 유용한 것으로 보이며, 특히 심방세동(AF)의 표지자로 알려져 있으며, 앞으로 더 많은 심방세동 표지자가 발굴되어 연구되어야 할 것이다.

• Clinical and Experimental Pediatrics
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• 제51권10호
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• pp.1102-1111
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• 2008

목 적: Resveratrol은 주로 포도나무의 과실이나 잎 부위에서 추출되는 성분으로, 주로 심질환에서 암 예방 효과, 항염증 효과, 항산화 효과의 기능이 밝혀지고 있다. 최근 성인에 대한 신경보호 효과가 있는 것으로 알려졌지만. 신생아에서 연구는 아직까지 없다. 그래서 본 연구에서는 resveratrol이 신생 백서의 저 산소 허혈 뇌손상에서 신경보호 효과가 있는지를 알아보고자 실험하였다. 방 법: 재태기간 18일된 태아 백서의 대뇌피질 세포를 배양하여 1% $O_2$ 배양기에서 저 산소 상태로 뇌세포손상을 유도하여 저 산소군, 저 산소 30분 전 resveratrol 투여군 (1, 10, $30{\mu}g/mL$)으로 나누어 정상 산소군과 비교하였다. 또한, 동물 모델에서는 생후 7일된 백서의 좌측 총 경동맥을 결찰한 후 저 산소 (8% $O_2$) 상태로 2.5시간 노출시켜서 저 산소 허혈 뇌 손상을 유발하였고, 뇌손상 전후 30분에 resveratrol을 체중 kg당 30 mg을 복막내로 투여하였다. 세포사멸사의 관련을 알아보기 위해 Bcl-2, Bax, caspase-3 primer를 이용한 실시간 중합효소연쇄반응과 동일 항체를 이용한 Western blotting을 시행하였다. 결 과: 태아 백서 뇌세포 배양 실험에서 저 산소군의 경우 Bcl-2의 발현이 정상 산소군에 비해 감소하였고, Bax의 발현과 caspase-3의 발현, 그리고 Bax/Bcl-2의 비율은 증가하였다. Reaveratrol을 투여한 실험군의 경우에서는 Bcl-2 발현은 증가하였고, Bax의 발현과 caspase-3의 발현, Bax/Bcl-2의 비율은 저 산소군에 비하여 감소하는 결과를 보였다. 또한 이는 저 산소 허혈 뇌손상 동물 모델에서도 같은 결과를 보였다. 결론: 본 연구에서 resveratrol은 주산기 저 산소 허혈 뇌손상에서 세포사멸사 작용의 억제를 통하여 신경보호 역할을 하는 것을 알 수 있었다.