• Biomolecules & Therapeutics
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• 제12권3호
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• pp.138-144
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• 2004

Therapeutic effect of a Kampo medicine, Choto-san, in patients with vascular dementia was demonstrated by a double-blind and placebo-controlled clinical trial. To clarify the therapeutic efficacy of Choto-san, anti-ischemic effect in mice, hypotensive effect in spontaneously hypertensive rats (SHR), anti-oxidative effects in vitro, and N-methyl-D-aspartate (NMDA) receptor-blocking activity using Xenopus oocytes were studied. (1) Pretreatment with Choto-san (0.75-6.O g/kg, P.O.) or a component herb Chotoko (Uncaria genus: 75 - 600 mg/kg, P.O.) prevented ischemia-induced impairment of spatial learning behaviour in mice. Indole alkaloids- and phenolic fractions extracted from Chotoko also improved significantly the learning deficit. (2) Subchronic administration of Choto-san (0.5 g/kg, p.o.) caused a significant hypotensive effects in SHR. (3) Choto-san, Chotoko, and the phenolic constituent, (-) epicatechin, significantly protected the NG108-15 cell injury induced by $H_20_2$ exposure in vitro and also inhibited lipid peroxidation in the brain homogenate. (4) Indole alkaloids, rhynchophylline and isorhynchophylline (1-100 uM), reversibly reduced NMDA-induced current in the receptor-expressed Xenopus oocytes. These results suggest that anti-vascular dementia effects of Choto-san are mainly due to the effect of Chotoko. From these results, it is possible to make a novel dietary supplement through several extraction steps from Chotoko.

• Journal of Chest Surgery
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• 제30권11호
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• pp.1142-1144
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• 1997

혈관륜이 있는 경우 드물게 동맥 식도루가 발생하여 대출혈이 발생할 수 있다. 42세 남자환자가 교통사고 후 7주간 비위관을 삽입하고 있던 중 상부 위장관 출혈이 발생하여 응급수술을 하였다. 수술 소견상 우측 쇄골하동맥 기시이상이 있었으며 오랜 비위관 상관으로 발생된 것으로 생각되는 동맥-식도루가 있어 이를 수술교정 하였다. 술후 환자상태는 안정 되었으나 술후 5일째 흉관 자극과 염증에 기인 하는 대동맥 봉합부위의 출혈이 발생하여 재수술을 하였고 의식불명 상태로 술후 8일째 사망하였다.

• Clinical and Experimental Pediatrics
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• 제45권5호
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• pp.560-567
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• 2002

주산기 뇌손상은 주로 급격한 저산소-허혈 손상에 의하는데 급격한 산소 공급의 차단은 oxidative phosphorylation을 정지 시켜서 뇌대사를 위한 에너지 공급이 차단되게 된다. 에너지 공급이 차단된 뇌세포는 뇌세포막에서 세포 내외의 이온 농도 차를 유지시키던 ATP-dependent $Na^{+}-K^{+}$ pump의 기능이 정지 되고, 세포 내외의 농도 차에 따라 $Na^{+}$, $Cl^{+}$, $Ca^{{+}{+}}$의 대규모 세포 내로 이동이 일어난다. 세포 내로 calcium 이온의 이동은 glutamate 수용체의 활성화에 의해서도 일나는데, 세포 내 calcium 이온의 증가는 protease, lipase, nuclease 등을 활성화 시켜 세포를 사망에 이르게 하는 연속적이고 다양한 생화학적 반응을 일으키게 된다. Glutamate는 대표적인 신경 전달 물질인데 저산소-허혈 손상 시 glutamate 수용체의 지나친 흥분은 미성숙 뇌에 뇌손상을 유발하는데, NMDA 또는 non-NMDA 수용체와 복합체를 형성하고 있는 calcium 이동 통로를 활성화 시켜 세포 내 calcium 이온을 증가시키고, 그 외에 metabotropic recetor는 G-protein의 활성화 등을 통해 뇌손상을 유발하는 다양한 생화학적 반응을 매개한다. 저산소-허혈 손상 후 재산소화와 재관류가 일어나면서 뇌세포의 지연성 사망(secondary neuronal death)이 일어나는데 이는 초기 손상 후 뒤이어 일어나는 다양한 생화학적 반응에 의하는데 다량의 산소 자유기 발생, nitric oxide의 생성, 염증 반응과 싸이토카인, 신경전도 물질의 과흥분 등이 관여하며, 신경 세포 사망은 세포괴사(necrosis)뿐 아니라 일부는 세포 사멸(apoptosis)로 알려진 의도된 세포 사망(programmed cell death)에 의한 것으로 생각되고 있다(Fig. 2).

• Journal of Korean Neurosurgical Society
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• 제50권4호
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• pp.370-376
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• 2011

Objective : Posttraumatic cerebral infarction (PTCI), an infarction in well-defined arterial distributions after head trauma, is a known complication in patients with severe head trauma. The primary aims of this study were to evaluate the clinical and radiographic characteristics of PTCI, and to assess the effect on outcome of decompressive hemicraniectomy (DHC) in patients with PTCI. Methods : We present a retrospective analysis of 20 patients with PTCI who were treated between January 2003 and August 2005. Twelve patients among them showed malignant PTCI, which is defined as PTCI including the territory of Middle Cerebral Artery (MCA). Medical records and radiologic imaging studies of patients were reviewed. Results : Infarction of posterior cerebral artery distribution was the most common site of PTCI. Fourteen patients underwent DHC an average of 16 hours after trauma. The overall mortality rate was 75%. Glasgow outcome scale (GOS) of survivors showed that one patient was remained in a persistent vegetative state, two patients were severely disabled and only two patients were moderately disabled at the time of discharge. Despite aggressive treatments, all patients with malignant PTCI had died. Malignant PTCI was the indicator of poor clinical outcome. Furthermore, Glasgow coma scale (GCS) at the admission was the most valuable prognostic factor. Significant correlation was observed between a GCS less than 5 on admission and high mortality (p<0.05). Conclusion : In patients who developed non-malignant PTCI and GCS higher than 5 after head injury, early DHC and duroplasty should be considered, before occurrence of irreversible ischemic brain damage. High mortality rate was observed in patients with malignant PTCI or PTCI with a GCS of 3-5 at the admission. A large prospective randomized controlled study will be required to justify for aggressive treatments including DHC and medical treatment in these patients.

• Journal of Chest Surgery
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• 제34권7호
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• pp.547-551
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• 2001

대동맥궁 재건술시 시행하는 완전순환정지는 술후 신경학적 손상과 관련된다. 저자들은 국소 순환으로 뇌와 심근혈류를 유지하면서 완전순환정지를 시키지 않고 시행한 변형 Norwood술식을 2명에서 시행하였기에 보고한다. 한 명은 체중이 3.1kg인 생후 13일된 여아로서 좌심형성부전증후군의 이형 환자였고 다른 한 명은 생후 38일된 체중 3.4kg의 남아로서 심한 대동맥 발육부전 및 축착증과 좌심실유출로 협착을 동반한 Taussig-Bing 기형이었다. 두 환아 모두 무명동맥에 직접 동맥캐뉼라를 삽관한 다음 저체온 상태에서 무명동맥과 관상동맥 혈류를 유지하면서 Norwood술식을 시행하였으며 두 명 모두 술후 신경학적, 심장 혹은 신기능 합병증은 없었다. 이 방법은 좌심형성부전증후군이나 대동맥 축착증 혹은 단절증과 같은 대동맥궁 기형 환자의 수술시 완전순환정지로 인해 발생될 수 있는 허혈성 손상으로부터 뇌와 심장을 보호할 수 있는 한 방법으로 생각된다.

• Toxicological Research
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• 제13권4호
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• pp.359-365
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• 1997

Many factors are known to be responsible for cerebral ischemic injury, such as excitatory neurotransmitters, increased intraneuronal calcium, or disturbance of cellular energy metabolism. Recently, oxygen free radicals, formed during ischemia/reperfusion, have been proposed as one of the main causes of ischemia/reperfusion injury. Therefore, to investigate the role of oxygen free radical during ischemia/reperfusion, in the present study the effect of endogenous oxygen free radical scavenger, superoxide dismutase / catalase(SOD / catalase) on the release of [$^3$H]-5-hydroxytryptamine([$^3$H]-5-HT) during hypoxia/reoxygenation in rat hippocampal slices was measured. The hippocampus was obtained from the rat brain and sliced 400 gm thickness with manual chopper. After 30 min's preincubation in the normal buffer, the slices were incubated for 20 min in a buffer containing [$^3$H]-5-HT(0.1 $\mu$M, 74 $\mu$Ci) for uptake, and washed. To measure the release of [$^3$H]-5-HT into the buffer, the incubation medium was drained off and refilled every ten minutes through a sequence of 14 tubes. Induction of hypoxia for 20 min (gassing it with 95% N$_2$/5% CO$_2$) was done in the 6th and 7th tube, and oxygen free radical scavenger, SOD / catalase was added 10 minutes prior to induction of hypoxia. The radioactivity in each buffer and the tissue were counted using liquid scintillation counter and the results were expressed as a percentage of the total activity. When slices were exposed to hypoxia for 20 min, [$^3$H]-5-HT release was markedly decreased and a rebound release of [$^3$H]-5-HT was observed on the post-hypoxic reoxygenation period. SOD / catalase did not changed the release of [$^3$H]-5-HT in control group, but inhibited the decrease of [$^3$H]-5-HT release in hypoxic period and rebound increase of [$^3$H]-5-HT in reoxygenation period. This result suggest that superoxide anion may play a role in the hypoxic-, and reoxygenation-induced change of [$^3$H]-5-HT release in rat hippocampal slices.

• Journal of Ginseng Research
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• 제31권1호
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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.

• Korean Journal of Acupuncture
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• 제35권4호
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• pp.187-202
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• 2018

Objectives : Non-invasive transcranial electrical stimulation is one of therapeutic interventions to change in neural excitability of the cortex. Transcranial electro-acupuncture (TEA) can modulate brain functions through changes in cortical excitability as a model of non-invasive transcranial electrical stimulation. Some composites of fermented Scutellaria baicalenis (FSB) can activate intercellular signaling pathways for activation of brain-derived neurotrophic factor that is critical for formation of neural plasticity in stroke patients. This study was aimed at evaluation of combinatory treatment of TEA and FSB on behavior recovery and cortical neural excitability in rodent focal stroke model. Methods : Focal ischemic stroke was induced by photothrombotic injury to the motor cortex of adult rats. Application of TEA with 20 Hz and $200{\mu}A$ in combination with daily oral treatment of FBS was given to stroke animals for 3 weeks. Motor recovery was evaluated by rotating bean test and ladder working test. Electrical activity of cortical pyramidal neurons of stroke model was evaluated by using multi-channel extracellular recording technique and thallium autometallography. Results : Compared with control stroke group who did not receive any treatment, Combination of TEA and FSB treatment resulted in more rapid recovery of forelimb movement following focal stroke. This combination treatment also elicited increase in spontaneous firing rate of putative pyramidal neurons. Furthermore expression of metabolic marker for neural excitability was upregulated in peri-infract area under thallium autometallography. Conclusions : These results suggest that combination treatment of TEA and FSB can be a possible remedy for motor recovery in focal stroke.

• Journal of Preventive Medicine and Public Health
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• 제54권1호
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• pp.55-62
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• 2021

Objectives: After heart disease, brain stroke (BS) is the second most common cause of death worldwide, underscoring the importance of understanding preventable and treatable risk factors for the outcomes of BS. This study aimed to model the survival of patients with BS in the presence of competing risks. Methods: This longitudinal study was conducted on 332 patients with a definitive diagnosis of BS. Demographic characteristics and risk factors were collected by a validated checklist. Patients' mortality status was investigated by telephone follow-up to identify deaths that may be have been caused by stroke or other factors (heart disease, diabetes, high cholesterol, etc.). Data were analyzed by the Lunn-McNeil approach at alpha=0.1. Results: Older age at diagnosis (59-68 years: adjusted hazard ratio [aHR], 2.19; 90% confidence interval [CI], 1.38 to 3.48; 69-75 years: aHR, 5.04; 90% CI, 3.25 to 7.80; ≥76 years: aHR, 5.30; 90% CI, 3.40 to 8.44), having heart disease (aHR, 1.65; 90% CI, 1.23 to 2.23), oral contraceptive pill use (women only) (aHR, 0.44; 90% CI, 0.24 to 0.78) and ischemic stroke (aHR, 0.52; 90% CI, 0.36 to 0.74) were directly related to death from BS. Older age at diagnosis (59-68 years: aHR, 21.42; 90% CI, 3.52 to 130.39; 75-69 years: aHR, 16.48; 90% CI, 2.75 to 98.69; ≥76 years: aHR, 26.03; 90% CI, 4.06 to 166.93) and rural residence (aHR, 2.30; 90% CI, 1.15 to 4.60) were directly related to death from other causes. Significant risk factors were found for both causes of death. Conclusions: BS-specific and non-BS-specific mortality had different risk factors. These findings could be utilized to prescribe optimal and specific treatment.

• BMB Reports
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• 제49권11호
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• pp.617-622
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• 2016

Oxidative stress is closely associated with various diseases and is considered to be a major factor in ischemia. NAD(P)H: quinone oxidoreductase 1 (NQO1) protein is a known antioxidant protein that plays a protective role in various cells against oxidative stress. We therefore investigated the effects of cell permeable Tat-NQO1 protein on hippocampal HT-22 cells, and in an animal ischemia model. The Tat-NQO1 protein transduced into HT-22 cells, and significantly inhibited against hydrogen peroxide ($H_2O_2$)-induced cell death and cellular toxicities. Tat-NQO1 protein inhibited the Akt and mitogen activated protein kinases (MAPK) activation as well as caspase-3 expression levels, in $H_2O_2$ exposed HT-22 cells. Moreover, Tat-NQO1 protein transduced into the CA1 region of the hippocampus of the animal brain and drastically protected against ischemic injury. Our results indicate that Tat-NQO1 protein exerts protection against neuronal cell death induced by oxidative stress, suggesting that Tat-NQO1 protein may potentially provide a therapeutic agent for neuronal diseases.