• The Korean Journal of Physiology and Pharmacology
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• v.8 no.2
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• pp.77-81
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• 2004

The loss of neurons and synaptic contacts following cerebral ischemia may lead to a synaptic plastic modification, which may contribute to the functional recovery after a brain lesion. Using synapsin I and GAP-43 as markers, we investigated the neuronal cell death and the synaptic plastic modification in the rat hippocampus of a middle cerebral artery occlusion (MCAO) model. Cresyl violet staining revealed that neuronal cell damage occurred after 2 h of MCAO, which progressed during reperfusion for 2 weeks. The immunoreactivity of synapsin I and GAP-43 was increased in the stratum lucidum in the CA3 subfield as well as in the inner and outer molecular layers of dentate gyrus in the hippocampus at reperfusion for 2 weeks. The immunoreactivity of phosphosynapsin was increased in the stratum lucidum in the CA3 subfield during reperfusion for 1 week. Our data suggest that the increase in the synapsin I and GAP-43 immunoreactivity probably mediates either the functional adaptation of the neurons through reactive synaptogenesis from the pre-existing presynaptic nerve terminals or the structural remodeling of their axonal connections in the areas with ischemic loss of target cells. Furthermore, phosphosynapsin may play some role in the synaptic plastic adaptations before or during reactive synaptogenesis after the MCAO.

• Biomedical Science Letters
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• v.13 no.2
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• pp.111-117
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• 2007

Temporary occlusion of the parent artery or feeding artery is an useful method in microsurgery for cerebrovascular diseases. The advantages of the temporary clipping for intracranial aneurysm surgery have already been proven by many experimental and clinical reports. Currently, there are two methods of temporary clipping: 1) intermittent clipping, 2) continuous clipping. In many previous studies, the intermittent, repeated clipping technique was reported to reduce ischemic damage to the brain, but it is still debated. On the other hand, a comparison of the histological changes on the arterial wall between each clipping method has not been sufficiently reported yet. So the authors performed experimental temporary clipping on the common carotid and femoral arteries of about 25 rats using the Sugita temporary mini-clip. The specimens were divided into two major groups and seven subgroups: Group I (I-1, I-2, I-3, I-4, intermittent clippings for 5 minutes were done once, twice, three times, and few times), and Group C (C-10, C-15, C-20, continuous clippings for 10, 15, 20 minutes, respectively). The reperfusion time after the temporary clipping was the same as the clipping duration. Under light microscope, the histological findings by Hematoxylin-Eosin staining were examined in all specimens, which were obtained at each time interval after temporary clipping. Then the histological changes of the arterial walls by two different methods were compared with the normal specimen. The results suggest that intermittent temporary clipping is less damaging on the arterial wall than single continuous clipping.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1733-1739
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• 2004

The water extract of Hwangryunhaedog-tang(HRHDT} has been traditionally used for treatment of ischemic heart and brain damage in oriental medicine. However, little is known about the mechanism by which the water extract of HRHDT rescues cells from these damages. This study was designed to investigate the protective mechanisms of HRHDT on hypoxia-induced cytotoxicity in H9c2 cardiomyoblast cells. Hypoxia, markedly decreased the viability of H9c2 cells, which was characterized with apparent apoptptic features such as chromatin condensation as well as fragmentation of genomic DNA and nuclei. However, HRHDT significantly reduced hypoxia-induced cell death and apoptotic characteristics. Also, HRHDT prevented the mitochondrial dysfunction including the disruption of mitochondria membrane permeability transition (MPT) and an increase in expression of anti-apoptotic Bcl-2 proteins in hypoxia-H9c2 cells. Taken together, this study suggests that the protective effects of the water extract of HRHDT against hypoxic damages may be mediated by the modulation of Bcl-2 and Bak expression.

• Journal of Chest Surgery
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• v.10 no.2
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• pp.281-294
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• 1977

Superior vena cava to pulmonary arterial shunting operation was made between the superior vena cava and the right pulmonary artery in the fashion of end-to-end anastomosis in 20 mongrel dogs. The experimental animals were divided into three group and blood flow in the superior vena cava was occluded for 20, 30 and 60 minutes respectively, and observations were made for the changes in caval pressure and cerebrospinal fluid pressure. And pathologic examinations were also performed. On occluding the caval blood flow, the superior vena caval pressure was sharply and immediately elevated from $103.5{\pm}19.8mmH_2O$ at thoracotomy to $556.4{\pm}86.lmmH_2O$ within 2 minutes to make its plateau thereafter, and the cerebrospinal fluid pressure followed closely the changes of the superior vena caval pressure in its level and pattern being elevated from $102.0{\pm}19.9mmH_2O$ to $490.5{\pm}79.9mmH_2O$. The drops of both the caval and cerebrospinal fluid pressures were definite and marked on opening the shunt flow through the anastomosis, but these postoperative pressures retained still higher ones above their levels measured at thoracotomy. The pathological examinations of the brain and the spinal cord were also performed in six animals. Characteristic changes uniformly seen in all area and in all animals were the findings of capillary congestion and perivascular edema. On the other hand, ischemic nerve cell changes were rather evident, revealing their degrees and extents being related to the prolongation of the time of caval occlusion which has followed by the sustained high pressures in both the superior vena and the cerebrospinal fluid. The experiment suggests the safety of this surgical procedure with minimal, if any, permanent damage as long as the occlusion of the caval blood flow is not prolonged beyond the expected.

• Journal of Korean Neurosurgical Society
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• v.29 no.5
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• pp.659-663
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• 2000

The motality rate of acute subdural hematoma(ASDH) associated with closed head injury is high in spite of recent advances in neurosurgery. Many variables in regard to outcome of ASDH have been assessed. But among them, intracranial pressure(ICP) control and the time interval between injury and operative evacuation are the only things that can be affected by doctor. We introduced a simple method to the management of ASDH for reducing the time interval between injury and operation. When the immediate decompressive operation of ASDH was impossible by any causes, we made a burr hole at the center of hematoma, usually on 2-3cm above temporal squama and 1-2cm behind coronal suture under local anesthesia before main operation. Partial hematoma evacuation was achieved through the burr hole and it was effective in preventing further worsening of patients neurological status before main operation. Prompt hematoma evacuation through the burr hole seemed to be effective in delaying secondary ischemic brain damage and made easy to closing the dura opening and replacement of the bone flap at the end of main decompressive operation. This easy method may reduce the time interval between injury and operation. We represent surgical technique with two cases of ASDH managed with this simple method.

• Journal of The Korean Society of Clinical Toxicology
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• v.18 no.1
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• pp.34-41
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• 2020

Purpose: This study evaluated aggressive hyperbaric oxygen therapy (HBOT) by understanding various exposure routes of acute carbon monoxide (CO) poisoning, the risk factors causing acute cardiovascular, and neurological toxicity caused by poisoning. Methods: A retrospective study was conducted based on the medical records of 417 acute CO poisoning patients who visited the emergency care unit from March 2017 to August 2019. The exposure routes, HBOT performance, age, sex, medical history (hypertension, diabetes mellitus, ischemic heart disease, heart failure), intentionality, loss of consciousness (LOC), intake with alcohol or sedatives, and initial test results (carboxyhemoglobin (COHb), troponin-I, electrocardiography, echocardiography, brain MRI) were examined. Comparative analysis of the clinical information was conducted between the groups that showed acute cardiovascular toxicity and neurological toxicity, and groups that did not. Results: Among 417 patients diagnosed with acute CO poisoning, 201 cases (48.2%) were intentional, and charcoal briquette was the most common route (169 patients (40.5%)). Two hundred sixteen cases (51.8%) were accidental, and fire was the most common route (135 patients (32.4%)). The exposure route was more diverse with accidental poisoning. Three hundred ninety-nine patients were studied for acute cardiovascular toxicity, and 62 patients (15.5%) were confirmed to be positive. The result was statistically significant in intentionality, LOC, combined sedatives, initial COHb, HTN, and IHD. One hundred two patients were studied for acute neurological toxicity, which was observed in 26 patients (25.5%). The result was statistically significant in age and LOC. Conclusion: Active HBOT should be performed to minimize damage to the major organs by identifying the various exposure routes of CO poisoning, risk factors for acute cardiovascular toxicity (intentionality, LOC, combined sedatives, initial COHb, HTN, IHD), and the risk factors for acute neurological toxicity (age, LOC).

• The Journal of Korean Medicine
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• v.24 no.2
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• pp.179-192
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• 2003

Objectives : Boyanghwanoh-tang (Buyanhaiwu-tang) has been used as a prescription for stroke, senile and vascular dementia, ischemic brain and heart damage in Oriental traditional medicine. However, there is little known about the mechanism by which the water extracts of Boyanghwanoh-tang (Buyanhaiwu-tang) rescue cells fromthese damages, and little is known about the protective mechanisms of Boyanghwanoh-tang (Buyanhaiwu-tang) on oxidative stress in neuronal cells. Therefore, we have investigated the role of Boyanghwanoh-tang (Buyanhaiwu-tang) on serum and glucose deprived apoptosis in PC12 cells. Methods : PC12 Cells have been used extensively as a model for studying the cellular and molecular effects of neuronal cells. The viability of cells was measured by MIT assay. We used DNA fragmentation and caspase 1, 2, 3, 6, 9-likeproteases activation assay. Transcriptional activation of NF-kB was assessed by using electrophoretic mobility shift assay. Results : Boyanghwanoh-tang (Buyanhaiwu-tang) rescued PC12 cells from apoptotic death by serum and glucose deprivation in a dose-dependent manner. The nuclear staining of PC12 cells clearly showed that Boyanghwanoh-tang (Buyanhaiwu-tang) attenuated nuclear condensation and fragmentation, which represent typical neuronal apoptotic characteristics. Boyanghwanoh-tang (Buyanhaiwu-tang) also prevents fragmentation of genomic DNA and activation of caspase 3-like protease in serum and glucose deprived PC12 cells. Furthermore, Boyanghwanoh-tang (Buyanhaiwu-tang) reduced the activation of NF-kB by serum and glucose-deprived apoptosis. Conclusions : These findings suggest that serum and glucose deprivation induces reduced glutathione (GSH) depletion, and consequently, apoptosis through endogenously produced reactive oxygen species in PC12 cells. Also, our data indicated that Boyanghwanoh-tang (Buyanhaiwu-tang) has protective effects against the serum and glucose deprived deaths of PC12 cells, which are mediated by the generation of GSH that, in turn, can reduce oxidative stress caused by reactive oxygen species (ROS) such as hydrogen peroxide.

• BMB Reports
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• v.49 no.11
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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.

• Proceedings of the Korean Environmental Health Society Conference
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• 2005.12a
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• pp.87-94
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• 2005

Results from previous studies revealed that metal level in the body is related to certain types of diseases. For example. serum copper level with chronic heart failure, iron and transferrin in the blood serum with acute cerebral vascular diseases, Zn in the CNS, lead with neurotoxicity, hypertension, genetic damage, arsenic with cancer skin lesion, Al with neurobehavioral function (cognitive impairment and memory disorder), and etc. The rate of stroke has increased in recent years and several metals were found to be responsible for causing stroke. This study compared several blood metal concentrations between stroke and non-stroke patients. Patients with stroke (116 samples) and non-stroke (111 samples including lowback pain and others) participated in this study. Total of 227 blood samples were collected and participants completed questionnaires regarding age, gender, occupation, residence, alcohol, smoking, and etc. To be qualified into the stroke group, patients have never experienced stroke previously. Subjects only included ischemic stroke and intracerebral hemorrhage patients diagnosed by brain CT and brain MRI. Patients with high risk of metal exposure such as herbal intake and job related exposure were excluded. 10ml of blood samples were analyzed by ICP-MS method at the Center of Nature and Science at Sangji University. Metal geometric mean (SD) concentrations in blood of study subjects showed higher values, 2.64-36.12%, than WHO reference values in Mn, Ni, Hg, Se, and As. Metal concentration in blood of stroke patients non-adjusted for potential confounders was higher except for Hg and also higher except for Ni in adjusted for potential confounders. Co was significantly higher in stroke patients (p=0.002) than non-stroke patients adjusted for potential confounders. Regression coefficient values of stroke patients was 0.17-8.25 in each metals. Odd ratio of stroke patients had 0.96 (Ni)-2.68 (Co) compared to non-stroke cases. This result means that Co increase of 1 raises the risk ratio of stroke by 2.86 times. Based on the results, metal concentration in blood seems to affect incidence of stroke.

• The Journal of Internal Korean Medicine
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• v.21 no.1
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• pp.116-125
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• 2000

Objectives : The aim of this study is to investigate that Sunghyangjeongki-San which has been frequently medicated in the early stage of stroke can protect against ischemic damage in rat brain Methods : Extracellular levels of amino acids(glutamate, aspartate, GABA, glycine, taurine, tyrosine, alanine), organic acids(pyruvate, lactate), and cerebral infarction volume were measured at the striatum of rats subjected to permanant focal cerebral ischemia induced by 2 hours of middle cerebral artery occiusion(MCAO). Rats were orally administered with Sunghyangjeongki-San at 30mins before MCAO and the microdialysate was collected by intracerebral microdialysis three times before MCAO and six times after MCAO at 20mins interval and analyzed by HPLC. After a microdialysis study, the brain was sliced and stained with cresyl violet buffer for the measurement of cerebral infarcted area and volume by image analyzer system Results : The concentrations of glutamate, aspartate, and tyrosine known as excitatory neurotransmitters were significantly decreased in Sunghyangjeongki-San group compared with control group, The concentrations of GABA, glycine, taurine and alanine known as inhibitory neurotransmitters were significantly increased in Sunghyangjeongki-San group compared with control group. The concentrations of pyruvate and lactate showed little significant change in Sunghyangjeongki-San group compared with control group. The measurement of cerebral infarcted area and volume by image analyzer system were significantly decreased in Sunghyangjeongki-San group compared with control group. Conclusions : Sunghyangjeongki-San can affect on protecting against cerebral ischemia by regulating extracellular levels of excitatory and inhibitory amino acid neurotransmitters and improve the conditions of the patients in the early stage of stroke.