• Toxicological Research
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• 제29권3호
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• pp.157-164
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• 2013

Although stroke is one of the leading causes of death and disability worldwide, preventive or therapeutic options are still limited. Therefore, a better understanding of the pathophysiological characteristics of this life-threatening disease is urgently needed. The incidence and prevalence of ischemic stroke are increased by exposure to certain types of xenobiotics, including heavy metals, suggesting the possible toxicological contribution of these compounds to the onset or aggravation of stroke. Among the potential targets, we have focused on alterations to cerebral endothelial cells (CECs), which play important roles in maintaining the functional integrity of brain tissue.

• 대한약침학회지
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• 제27권2호
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• pp.162-171
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• 2024

Objectives: Electroacupuncture (EA) has been demonstrated to aid stroke recovery. However, few investigations have focused on identifying the potent molecular targets of EA by comparing EA stimulation between naïve and disease models. Therefore, this study was undertaken to identify the potent molecular therapeutic mechanisms underlying EA stimulation in ischemic stroke through a comparison of mRNA sequencing data obtained from EA-treated naïve control and ischemic stroke mouse models. Methods: Using both naïve control and middle cerebral artery occlusion (MCAO) mouse models, EA stimulation was administered at two acupoints, Baihui (GV20) and Dazhui (GV14), at a frequency of 2 Hz. Comprehensive assessments were conducted, including behavioral evaluations, RNA sequencing to identify differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction (PPI) network analysis, and quantitative real-time PCR. Results: EA stimulation ameliorated the ischemic insult-induced motor dysfunction in mice with ischemic stroke. Comparative analysis between control vs. MCAO, control vs. control + EA, and MCAO vs. MCAO + EA revealed 4,407, 101, and 82 DEGs, respectively. Of these, 30, 7, and 1 were common across the respective groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed upregulated DEGs associated with the regulation of inflammatory immune response in the MCAO vs. MCAO + EA comparison. Conversely, downregulated DEGs in the control vs. control + EA comparison were linked to neuronal development. PPI analysis revealed major clustering related to the regulation of cytokines, such as Cxcl9, Pcp2, Ccl11, and Cxcl13, in the common DEGs of MCAO vs. MCAO + EA, with Esp8l1 identified as the only common downregulated DEG in both EA-treated naïve and ischemic models. Conclusion: These findings underscore the diverse potent mechanisms of EA stimulation between naïve and ischemic stroke mice, albeit with few overlaps. However, the potent mechanisms underlying EA treatment in ischemic stroke models were associated with the regulation of inflammatory processes involving cytokines.

• 대한한의학회지
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• 제21권1호
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• pp.84-90
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• 2000

Background and Purpose: Stroke in young adults is relatively uncommon. Only 3.7-14.4% of all strokes occur in patients aged 15-45 years. Stroke in young adults has more various and diverse possible causes than stroke in the elderly. We studied to gain further insight into both pathogenic and etiologic determinants in young adults with stroke. Methods : We retrospectively reviewed the medical records of 230 young patients aged 15-45 years who were admitted to the 2nd internal medicine department of Kyung Hee Oriental Medical Center with a diagnosis of stroke between May 1995 and May 1999. We analysed clinical features and diagnostic tests, such as brain imaging, cerebral angiography, echocardiography, 24 hours holter monitoring and other laboratory tests. Results : 1. Of 230 young patients with stroke aged 15-45 years(176 males(76.5%) and 54 females(23.5%)), 140 patients(60.9%) showed ischemic stroke and 90 patients(39.1 %) showed hemorragic stroke. 2. The most prevalent age group was from 40 to 45 years with 142 patients(61.7%) 3. The most frequent site of 140 ischemic stroke was MCA territory in 93 cases(66.4%) and Multiple, VA territory, PCA territory, ACA territory in order of frequency. 4. The most frequent site of 90 hemorrhagic stroke was basal galglia hemorrhage 57 cases(63.3%) and subcortical 13 cases(14.5%), pons, thalmus, subarachnoid, cerebellum in order of frequency. 5. The causes of hemorrhagic stroke were hypertension 49 cases(54.5%), arteriovenous malformation 7 cases(7.8%), ruptured aneurysm 4 cases(4.5%), angioma 3 cases(3.3%). 6. The risk factors of ischemic stroke were smoking, alcohol drinking, hyperlipidemia, hypertension, obesity, heart disease, history of CVA, diabetes mellitus, in order of frequency. 7. The comparison of risk factors between ischemic and hemorrhagic stroke: hypertension was prevalent in hemorrhagic stroke, heart disease and history of CVA were prevalent in ischemic stroke. Conclusions: From the above results, we found that stroke in young adults had various possible causes. Young adults with stroke deserve an extensive but tailored evaluation which include angiography and echocardiography for diagnosis.

• Biomolecules & Therapeutics
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• 제30권1호
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• pp.55-63
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• 2022

Oleanolic acid (OA), a natural pentacyclic triterpenoid, has been reported to exert protective effects against several neurological diseases through its anti-oxidative and anti-inflammatory activities. The goal of the present study was to evaluate the therapeutic potential of OA against acute and chronic brain injuries after ischemic stroke using a mouse model of transient middle cerebral artery occlusion (tMCAO, MCAO/reperfusion). OA administration immediately after reperfusion significantly attenuated acute brain injuries including brain infarction, functional neurological deficits, and neuronal apoptosis. Moreover, delayed administration of OA (at 3 h after reperfusion) attenuated brain infarction and improved functional neurological deficits during the acute phase. Such neuroprotective effects were associated with attenuation of microglial activation and lipid peroxidation in the injured brain after the tMCAO challenge. OA also attenuated NLRP3 inflammasome activation in activated microglia during the acute phase. In addition, daily administration of OA for 7 days starting from either immediately after reperfusion or 1 day after reperfusion significantly improved functional neurological deficits and attenuated brain tissue loss up to 21 days after the tMCAO challenge; these findings supported therapeutic effects of OA against ischemic stroke-induced chronic brain injury. Together, these findings showed that OA exerted neuroprotective effects against both acute and chronic brain injuries after tMCAO challenge, suggesting that OA is a potential therapeutic agent to treat ischemic stroke.

• 대한본초학회지
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• 제20권3호
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• pp.75-81
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• 2005

Objectives : In brain disorders such as ischemic stroke, the final outcome depends largely on the duration and the degree of the ischemia as well as the susceptibility of various cell types in the affected brain region. In the present study, the effects of Nodus Nelumbinis Rhizomatis Extract(NNRe) were tested for the anti-oxidative action of rCBF. Methods : Regional cerebral blood flow(rCBF) were determined by LDF methods. LDF allows for real time, noninvasive, continuous recordings of local CBF. The LDF method has been widely used to trace hemodynamic changes in the superficial or the deep brain structures in experimental stroke research. Results : NNRe treatment showed no change on rCBF in methylene blue, ODQ and L-NNA pretreated rats. 120 minutes of MCAO and followed reperfusion, 0.1% concentration of NNR treatment improved the altered cerebral hemodynamics of cerebral ischemic by increasing rCBF. Conclusions : The ischemia/reperfusion induced oxidative stress may have contributed to cerebral damage in rats, and the present study provides clear evidences for the beneficial effect of NNR on ischemia/reperfusion induced brain injury.

• Biomolecules & Therapeutics
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• 제28권2호
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• pp.152-162
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• 2020

Cerebral ischemia exhibits a multiplicity of pathophysiological mechanisms. During ischemic stroke, the reactive oxygen species (ROS) concentration rises to a peak during reperfusion, possibly underlying neuronal death. Recombinant human erythropoietin (EPO) supplementation is one method of treating neurodegenerative disease by reducing the generation of ROS. We investigated the therapeutic effect of PEGylated EPO (P-EPO) on ischemic stroke. Mice were administered P-EPO (5,000 U/kg) via intravenous injection, and middle cerebral artery occlusion (MCAO) followed by reperfusion was performed to induce in vivo ischemic stroke. P-EPO ameliorated MCAO-induced neurological deficit and reduced behavioral disorder and the infarct area. Moreover, lipid peroxidation, expression of inflammatory proteins (cyclooxygenase-2 and inducible nitric oxide synthase), and cytokine levels in blood were reduced by the P-EPO treatment. In addition, higher activation of nuclear factor kappa B (NF-κB) was found in the brain after MCAO, but NF-κB activation was reduced in the P-EPO-injected group. Treatment with the NF-κB inhibitor PS-1145 (5 mg/kg) abolished the P-EPO-induced reduction of infarct volume, neuronal death, neuroinflammation, and oxidative stress. Moreover, P-EPO was more effective than EPO (5,000 U/kg) and similar to a tissue plasminogen activator (10 mg/kg). An in vitro study revealed that P-EPO (25, 50, and 100 U/mL) treatment protected against rotenone (100 nM)-induced neuronal loss, neuroinflammation, oxidative stress, and NF-κB activity. These results indicate that the administration of P-EPO exerted neuroprotective effects on cerebral ischemia damage through anti-oxidant and anti-inflammatory properties by inhibiting NF-κB activation.

• 대한한방내과학회지
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• 제29권3호
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• pp.629-640
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• 2008

Objective : The purpose of this study was to investigate the neuroprotective effect of Jukryuk on 4-vessel occlusion(4-VO) and middle cerebral artery (MCA) ischemia. Method : After administration of Jukryuk, we compared the Jukryuk-treated group, the control, and the sham groups, in view of several points as follows 1) We evaluated the damage characterized by coagulative cell change of pyramidal neurons and pronounced gliosis in each group 2) We counted the number of normal pyramidal shapes after ischemia in each group 3) Immunohistochemistry (cyclooxygenase-2) 4) In focal ischemic injury model, we measured the volume of ischemic area Results : In this experiment, the effect of Jukryuk was determined to be protecting neuron cell shape, reducing the number of neuron cells damaged by ischemia and the volume of the ischemic area. In immunohistochemistry, Jukryuk reduced cyclooxygenase-2 expression Conclusions : According to this study, Jukryuk can protect neuron cells from injury by cerebrovascular ischemia.

• 대한한의학회지
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• 제22권3호
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• pp.81-91
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• 2001

Objectives : This study was prepared for investigating the clinical features of stroke patients. Methods : We retrospectively reviewed the medical records of 177 patients who were admitted to the Dept. of Internal Medicine, College of Oriental Medicine, Kyungwon University with a diagnosis of stroke from Jan. I, 1999 to Dec. 31, 1999. Results : Ischemic stroke (74.0%) was more common than hemorrhagic stroke (19.8%). The proportion of males was 53.7%, of females was 46.3%, and the most prevalent age group is those in their sixties. Cerebral infarction was most frequently noticed in MCA territory, hemorrhage in putamen. Hypertension was the most common preceding disease, followed by diabetes mellitus. The rate of recurrence was high in cerebral infarction. The onset mode of cerebral infarction was sleeping and rising and of cerebral hemorrhage was acting. Most patients visited the hospital within 24 hours. The most common symptoms at admission were motor weakness and speech disorder. The most common complication was urinary tract infection. Admission period was 29.5 days. Physical treatment from onset in cerebral infarction and in cerebral hemorrhage was 17.4 and 22.0 days, respectively. Conclusions : Our study of CVA patients was similar to previous studies from 1994 to 1998. In most cases, western and oriental treatment and medicine were given synthetically. Prescription of sasang constitutional medicine had wide application.

• Journal of Korean Neurosurgical Society
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• 제50권6호
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• pp.492-496
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• 2011

Objective : Direct revascularization surgery is regarded as the most effective method of treatment of adults with moyamoya disease. These patients, however, have a higher risk of perioperative ischemic complications than do patients with atherosclerotic stroke, and are at risk for ischemic complications in the hemisphere contralateral to the one operated on. We investigated the incidence and risk factors for ischemic stroke in the contralateral hemisphere after surgical treatment of adults with moyamoya disease. Methods : We retrospectively reviewed the medical records and results of neuroimaging studies on 79 hemispheres of 73 consecutive patients with adult moyamoya disease ($mean{\pm}SD$ age, $37.96{\pm}11.27$ years; range, 18-62 years) who underwent direct bypass surgery over 6 years. Results : Ischemic complications occurred in 4 of 79 (5.1%) contralateral hemispheres, one with Suzuki stage 3 and three with Suzuki stage 4. Three patients showed posterior cerebral artery (PCA) involvement by moyamoya vessels. Advanced stage of moyamoya disease (Suzuki stages 4/5/6; $p$=0.001), PCA involvement ($p$=0.001) and postoperative hypotension (mean arterial blood pressure <80% of preoperative mean arterial blood pressure) on the first ($p$<0.0001) and second ($p$=0.003) days after surgery were significantly correlated with postoperative contralateral ischemic complications. Conclusion : In patients with advanced moyamoya disease and involvement of the PCA, intentional hypotension can result in ischemic stroke in the hemisphere contralateral to the one operated on. Careful control of perioperative blood pressure is crucial for good surgical results.

• 대한중풍순환신경학회지
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• 제6권1호
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• pp.1-7
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• 2005

Objectives: Chungpyesagan-tang is a famous oriental Objectives: medicine treatment frequently used to stroke in Korea. The objective of this study is to evaluate the mechanism of the therapeutic effect of Chungpyesagan-tang on stroke in rat. Methods: We compared the difference in regional cer Methods: ebral blood flow, nitric oxide (NO) synthesis between the control and the Chungpyesagan-tang-treated group after ligating middle cerebral artery. Results: In our study, cerebral blood flow increased more in the stroke rats which had been fed by Chungpyesagan-tang than in the control. Chungpyesagan-tang induced vascular NO synthesis, but had no effect on neuronal NO synthesis. Conclusion: The mechanism of Chngpyesagan-tang's therapeutic effect on ischemic stroke could be explained by increasing cerebral blood flow and vascular NO synthesis.