• Biomolecules & Therapeutics
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• 제25권3호
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• pp.272-278
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• 2017

Fucoidan has been reported to exhibit various beneficial activities ranging from to antivirus and anticancer properties. However, little information is available about the effects of fucoidan on cerebral ischemia-reperfusion injury (IRI). Our study aimed to explore the effects of fucoidan on cerebral IRI, as well as the underlying mechanisms. Sprague-Dawley (SD) rats were randomly subjected to four groups: Sham, IRI+saline (IRI+S), IRI+80 mg/kg fucoidan (IRI+F80), and IRI+160 mg/kg fucoidan (IRI+F160). Fucoidan (80 mg/kg or 160 mg/kg) was intraperitoneally injected from 7 days before the rats were induced to cerebral IRI model with middle cerebral artery occlusion (MCAO) method. At 24 h after reperfusion, neurological deficits and the total infarct volume were determined. The levels of inflammation-associated cytokines (interleukin (IL)-$1{\beta}$, IL-6, myeloperoxidase (MPO), and tumor necrosis factor (TNF)-${\alpha}$), oxidative stress-related proteins (malondialdehyde (MDA) and superoxide dismutase (SOD)) in the ischemic brain were measured by enzyme-linked immunosorbent assay (ELISA). Besides, the levels of apoptosis-related proteins (p-53, Bax, and B-cell lymphoma (Bcl)-2) and mitogen-activated protein kinase (MAPK) pathway (phosphorylation-extracellular signal-regulated kinase (p-ERK), p-c-Jun N-terminal kinase (JNK), and p-p38) were measured. Results showed that administration of fucoidan significantly reduced the neurological deficits and infarct volume compared to the IRI+S group in a dose-dependent manner. Also, fucoidan statistically decreased the levels of inflammation-associated cytokines, and oxidative stress-related proteins, inhibited apoptosis, and suppressed the MAPK pathway. So, Fucoidan plays a protective role in cerebral IRI might be by inhibition of MAPK pathway.

• 대한본초학회지
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• 제29권5호
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• pp.23-30
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• 2014

Objectives : Dodam-tang has been reported to have a control effect against the hyperlipidemia and thrombosis. Based upon these previous reports, this study investigates the effects of Dodam-tang on the cerebral ischemic damage of the hyperlipidemic rats. Methods : Hyperlipidemia was induced by the beef tallow 30% diet for 14 days on Sprague-Dawley rats. Ischemic damage was induced by the middle cerebral artery occlusion (MCAO) for 2 hours with the intraluminal thread method. Then water extract of Dodam-tang was administered daily for 5 days. The effect of Dodam-tang was evaluated with the serum lipids, infarct volume and edema percentage, and immunohistochemical expressions of iNOS, MMP-9, and GFAP in the brain tissue. Results : The obtained results were as follows; Dodam-tang reduced significantly the infarct size in a TTC-stained 5th brain section of the hyperlipidemic MCAO rats. Dodam-tang suppressed the infarct volume of the hyperlipidemic MCAO rats, but not significant statistically. Dodam-tang suppressed the edema percentage of the hyperlipidemic MCAO rats significantly in the brain tissue. Dodam-tang suppressed significantly the iNOS expression in the cerebral penumbra and caudate putamen of the hyperlipidemic MCAO rats. Dodam-tang suppressed significantly the MMP-9 expression in the cerebral penumbra of the hyperlipidemic MCAO rats. Dodam-tang suppressed significantly the GFAP-expressed atrocytes in the cerebral penumbra of the hyperlipidemic MCAO rats. Conclusions : These results suggest that Dodam-tang suppresses the brain edema formation through the suppression of the iNOS, MMP-9 and GFAP, but the neuroprotective effect against the cerebral infarct are not distinct.

• Journal of Korean Neurosurgical Society
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• 제50권3호
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• pp.185-190
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• 2011

Objective : To investigate the efficacy of extracranial-intracranial (EC-IC) bypass surgery using a radial artery interposition graft (RAIG) for surgical management of cerebrovascular diseases. Methods : The study involved a retrospective analysis of 13 patients who underwent EC-IC bypass surgery using RAIG at a single neurosurgical institute between 2003 and 2009. The diseases comprised intracranial aneurysm (n=10), carotid artery occlusive disease (n=2), and delayed stenosis in the donor superficial temporal artery (STA) following previous STA-middle cerebral artery bypass surgery (n=1). Patients were followed clinically and radiographically. Results : Bypass surgery was successful in all patients. At a mean follow-up of 53.4 months, the short-term patency rate was 100%, and the long-term rate was 92.3%. Twelve patients had an excellent clinical outcome of Glasgow Outcome Scale (GOS) 5, and one case had GOS 3. Procedure-related complications were a temporary dysthesia on the graft harvest hand (n=1) and a hematoma at the graft harvest site (n=1), and these were treated successfully with no permanent sequelae. In one case, spasm occurred which was relieved with the introduction of mechanical dilators. Conclusion : EC-IC bypass using a RAIG appears to be an effective treatment for a variety of cerebrovascular diseases requiring proximal occlusion or trapping of the parent artery.

• Nuclear Medicine and Molecular Imaging
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• 제42권1호
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• pp.8-16
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• 2008

목적: 내경동맥 또는 중대뇌동맥의 죽상 동맥 경화증 환자에서의 두개외강-내강 우회로술(이하 우회로술) 후의 연속적인 혈류 역학적 변화를 $^{99m}Tc$-ECD 아세타졸아마이드 부하 뇌혈류 단일 광자 방출 전산화 단층 촬영(이하 아세타졸아마이드 부하 SPECT)으로 평가하여 중대뇌 동맥의 각 분지별 영역에 대한 우회로술의 혈류역학적 개선효과를 알아보고자 하였다. 대상 및 방법: 전향적 방법으로 최근 3개월 내에 혈관 폐색성 징후가 발생하여 우회로술을 시행받은 환자를 대상으로 수술 전과 수술 1 주 후, 3-6 개월 후에 아세타졸아마이드 부하 SPECT를 시행하였다. 영상 분석을 위해 SPM의 SPECT 표준 뇌에 공간 정규화한 후 Anatomical Automated Labeling으로 중대뇌동맥의 지배를 받는 양측 전두, 측두, 두정 영역에 관심 구역을 설정하여 각 관심 영역별로 뇌혈류 지표(PI; $C_{region}/C_{ipsilateral\;cerebellum}$) 및 뇌혈관 예비능 지표$((PI_{acetazolamide}-PI_{basal})/PI_{basal})$로 정하여 이들 지표의 수술 전후 변화를 평가하였다. 결과한 측에 성공적인 우회로술을 시행한 환자 17 명(남:여=12:5, 나이 $53{\pm}2$세)을 분석하였다. 전체적으로 뇌혈류는 수술 1 주 후 유의하게 증가하나 3-6 개월 후 감소하여 수술 이전의 수준으로 유지되었으며 ($1.01{\pm}0.09{\rightarrow}1.06{\pm}0.09}{\rightarrow}1.02{\pm}0.10,\;p=0.005$) 뇌 혈관 예비능은 수술 1 주 후 유의하게 증가한 이후 유의하지는 않으나, 3-6개월 이후까지 계속 호전되었다($-0.14{\pm}0.05{\rightarrow}-0.07{\pm}0.04{\rightarrow}0.05{\pm}0.05,\;p=0.004$). 각 뇌 영역별로 뇌혈류는 두정 영역에서 수술 직후 증가하였다가($1.12{\pm}0.09{\rightarrow}1.18{\pm}0.09,\;p=0.003$) 수술 3-6개월 이후 감소하여($1.12{\pm}0.09,\;p=0.003$) 수술 이전의 수준으로 유지되었다. 뇌혈관 예비능은 수술 측의 전두 영역($-0.15{\pm}0.07{\rightarrow}0.08{\pm}0.05$), 두정 영역($-0.16{\pm}0.07{\rightarrow}-0.07{\pm}0.05$)에서 모두 수술 직후 유의하게 증가하였고(p<0.01) 이후 유의하지는 않으나 3-6개월까지 계속 호전되었다. 결론: 성공적인 우회로술 후 뇌혈류는 전체적으로 유의한 변화가 없었으나 뇌혈관 예비능은 중대뇌동맥 영역 전체에 걸쳐 수술 후 단기간에 유의한 호전을 보였으며 장기간 유지되었다. 따라서 뇌혈관 예비능의 호전여부는 우회로술에 의해 증가된 뇌관류압을 평가할 수 있는 중요한 지표로 생각되며 향후 우회로술에 의한 뇌졸중 재발방지 효과를 알아보기 위해 뇌혈관 예비능의 변화와 예후와의 상관관계에 대한 연구가 필요하리라 생각된다.

• The Korean Journal of Pain
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• 제21권1호
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• pp.33-37
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• 2008

Background: Cerebral blood vessels are innervated by sympathetic nerves from the superior cervical ganglion (SCG). The purpose of the present study was to evaluate the neuroprotective effect of superior cervical sympathetic ganglion block in rats subjected to permanent focal cerebral ischemia. Methods: Thirty male Sprague-Dawley rats (270-320 g) were randomly assigned to one of three groups (control, lidocaine and ropivacaine). A brain injury was induced in all rats by middle cerebral artery occlusion with a nylon thread. The animals of the local anesthetic group received $30{\mu}l$ of 2% lidocaine or 0.75% ropivacaine in the SCG. Neurologic scores were assessed 24 hours after brain injury. Brain samples were then collected. The infarct and edema ratios were measured by 2.3.5-triphenyltetrazolium chloride staining. Results: There were no differences in the death rates, neurologic scores, or infarction and edema ratios between the three groups. Conclusions: These findings suggest that superior cervical sympathetic ganglion block may not influence the brain damage induced by permanent focal cerebral ischemia in rats.

• Journal of Korean Neurosurgical Society
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• 제40권3호
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• pp.180-185
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• 2006

Objective : Middle cerebral artery occlusion[MCAO] has widely been used to produce ischemic brain lesions. The lesions induced by MCAO tend to be variable in size because of the variance in the collateral blood supply found in the mouse brain. To establish a less invasive and reproducible focal ischemia model in mice, we modified the technique used for rat photo thrombosis model. Methods : Male C57BL/6 mice were subjected to focal cerebral ischemia by photothrombosis of cortical microvessels. Cerebral infarction was produced by intraperitoneal injection of Rose Bengal, a photosensitive dye and by focal illumination through the skull. Motor impairment was assessed by the accelerating rotarod and staircase tests. The brain was perfusion-fixed for histological determination of infarct volume four weeks after stroke. Results : The lesion was located in the frontal and parietal cortex and the underlying white matter was partly affected. A relatively constant infarct volume was achieved one month after photothrombosis. The presence of the photothrombotic lesion was associated with severe impairment of the motor performance measured by the rotarod and staircase tests. Conclusion : Photothrombotic infarction in mice is highly reproducible in size and location. This procedure can provide a simple method to produce cerebral infarction in a unilateral motor cortex lesion. In addition, it can provide a suitable model for study of potential neuroprotective and therapeutic agents in human stroke.

• Biomolecules & Therapeutics
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• 제25권2호
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• pp.149-157
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• 2017

The interleukin-1 receptor antagonist (IL-1RA) is a potential stroke treatment candidate. Intranasal delivery is a novel method thereby a therapeutic protein can be penetrated into the brain parenchyma by bypassing the blood-brain barrier. Thus, this study tested whether intranasal IL-1RA can provide neuroprotection and brain penetration in transient cerebral ischemia. In male Sprague-Dawley rats, focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 1 h. The rats simultaneously received 50 mg/kg human IL-1RA through the intranasal (IN group) or intraperitoneal route (IP group). The other rats were given 0.5 mL/kg normal saline (EC group). Neurobehavioral function, infarct size, and the concentration of the administered human IL-1RA in the brain tissue were assessed. In addition, the cellular distribution of intranasal IL-1RA in the brain and its effect on proinflammatory cytokines expression were evaluated. Intranasal IL-1RA improved neurological deficit and reduced infarct size until 7 days after MCAO (p<0.05). The concentrations of the human IL-1RA in the brain tissue 24 h after MCAO were significantly greater in the IN group than in the IP group (p<0.05). The human IL-1RA was confirmed to be co-localized with neuron and microglia. Furthermore, the IN group had lower expression of $interleukin-1{\beta}$ and tumor necrosis $factor-{\alpha}$ at 6 h after MCAO than the EC group (p<0.05). These results suggest that intranasal IL-1RA can reach the brain parenchyma more efficiently and provide superior neuroprotection in the transient focal cerebral ischemia.

• 대한본초학회지
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• 제29권3호
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• pp.71-78
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• 2014

Objectives : This study evaluates the neuroprotective effects of Sopung-tang, a mixture of Notopterygii Rhizoma, Saposhnikoviae Radix, Angelicae Gigantis Radix, Cnidii Rhizoma, Hoelen, Aurantii Nobilis Pericarpium, Pinelliae Tuber, Linderae Radix, Angelicae Dahuricae Radix, Cyperi Rhizoma, Cinnamomi Ramulus, Asari Radix, Glycyrrhizae Radix on the cerebral infarct combined with hyperlipidemia. Method : The hyperlipidemia was induced by the beef tallow 30% diet for 14 days on Sprague-Dawley rats. The cerebral infarct was induced by the middle cerebral artery occlusion (MCAO) for 2 hours with intraluminal thread method. Then the water extract of Sopung-tang was administered a day for 5 days at 3 hours after the cerebral infarct by MCAO. Effect of Sopung-tang was evaluated with the infarct volume and edema percentage by a TTC-stained brain section, and the expressions of Bax and Bcl-2 in the brain tissue by a immunohistochemical stain method. Results : Sopung-tang reduced the infarct size partly in a TTC-stained brain section of the hyperlipidemic MCAO rats. Sopung-tang reduced the infarct volume of the hyperlipidemic MCAO rats significantly. Sopung-tang reduced the edema percentage of the hyperlipidemic MCAO rats, but not significant statistically. Sopung-tang suppressed the Bax expressions in the cerebral penumbra and caudate putamen of the hyperlipidemic MCAO rats significantly. Sopung-tang upregulated the Bcl-2 expression in the caudate putamen of the hyperlipidemic MCAO rats. Conclusion : These results suggest that Sopung-tang plays an anti-apoptotic neuroprotective effect through the suppression of Bax and up-regulation of Bacl-2 expressions in the brain tissues.

• The Journal of Korean Physical Therapy
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• 제13권3호
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• pp.529-535
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• 2001

The purpose of this study was to test that the exercise adaptive training enhance behavioral outcome significantly after focal brain ischemia in rats. After occlusion of middle cerebral artery in rats, they were housed in individual standard cages fur 24 hours. The control group was sacrificed 24 hours after ischemic event. The experimental group I was housed in standard cages for 7days. The experimental group ll was housed in enriched environment and had got exercise adaptive training fur 7days. The rats were examined five motor behavioral tests. In motor behavioral tests :postural reflex test, limb placement test, beam-walking test, rotarod test, horizontal wire test. The outcomes of control group and group I were significantly lower than the group II. The conclusion was that exercise adaptive training induced functional repair.

• BMB Reports
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• 제56권2호
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• pp.90-95
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• 2023

Mitochondria are important organelles that regulate adenosine triphosphate production, intracellular calcium buffering, cell survival, and apoptosis. They play therapeutic roles in injured cells via transcellular transfer through extracellular vesicles, gap junctions, and tunneling nanotubes. Astrocytes can secrete numerous factors known to promote neuronal survival, synaptic formation, and plasticity. Recent studies have demonstrated that astrocytes can transfer mitochondria to damaged neurons to enhance their viability and recovery. In this study, we observed that treatment with mitochondria isolated from rat primary astrocytes enhanced cell viability and ameliorated hydrogen peroxide-damaged neurons. Interestingly, isolated astrocytic mitochondria increased the number of cells under damaged neuronal conditions, but not under normal conditions, although the mitochondrial transfer efficiency did not differ between the two conditions. This effect was also observed after transplanting astrocytic mitochondria in a rat middle cerebral artery occlusion model. These findings suggest that mitochondria transfer therapy can be used to treat acute ischemic stroke and other diseases.