• Journal of Korean Neurosurgical Society
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• v.38 no.3
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• pp.221-226
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• 2005

Objective : Reactive oxygen metabolites and polymorphonuclear leukocytes have been implicated in the pathophysiology of reperfusion injury. The mechanisms involved in superoxide-mediated leukocyte adherence remain unclear, however, nitric oxide[NO] may contribute to this response. The present study is undertaken to elucidate mechamisms controlling NO based mechanisms that regulated leukocyte-endothelial interactions in the cerebral vasculature after global cerebral ischemia and reperfusion. Methods : Pial venular leukocyte adherence of anesthetized newborn piglets was quantified by in situ fluorescence videomicroscopy through closed cranial windows during basal conditions and during 2hours of reperfusion after global ischemia induced by 9minutes of asphyxia. Nitric oxide synthase[NOS] was inhibited by local window superfusion of L-nitroarginine[NA]; superfusion of sodium nitroprusside[SNP] was used to donate NO. Results : The mean number of adherent leukocytes to cerebral venules in the 9minutes asphyxia and 2hours reperfusion group were $161{\pm}19$ compared with $13{\pm}4$ in the nonasphyxial group. Superfusion of L-NA through the cranial window for 2hours resulted in leukocyte adherence similar to that observed during the initial 2hours of reperfusion after asphyxia. Leukocyte adherence was not additionally increased in asphyxic animal treated with L-NA. SNP inhibited asphyxia induced leukocyte adherence back to control levels. Conclusions : Nitric oxide inhibits leukocyte adherence to cerebral venules during the initial hours of reperfusion after asphyxia, and that NO supplementation inhibit asphyxia induced leukocyte adherence back to control levels. These results indicate that NO is an important factor in ischemia-reperfusion induced leukocyte adherence.

• Journal of Korean Neurosurgical Society
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• v.29 no.10
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• pp.1289-1295
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• 2000

Purpose : Recent evidence suggests a possible role for leukocytes in brain injury following ischemia and reperfusion. This study examined the temporal profile of ischemic tissue damage and leukocyte response after transient middle cerebral artery occlusion(MCAO) with reperfusion in the mouse. Methods : Focal cerebral ischemia was made by temporary occluding of the stem of the proximal MCA. Two groups of the mouse were investigated : (1) sham operation(n＝10), and (2)those having the arterial occlusion released after 90 minute(n＝20). By 4 hours(n＝10) and 24 hours(n＝10) after the onset of ischemia-reperfusion, fluorescein videoimages were under-taken in the pial venules of the mouse using a closed cranial window technique. Rhodamine 6G was administered as a $80-100{\mu}l/min$ i.v. loading dose and a $30-40{\mu}l/min$ i.v. maintenance dose in saline to selectively label circulating leukocytes. Neuropathologic evaluation for brain injury was accomplished using the histochemical stain 2,3,5-triphen-yltetrazolium chloride(TTC) and hematoxylin and eosin(H & E) stain. Results : The mean number of adherent leukocytes to cerebral venules in the 90 minutes MCAO and 24 hours reperfusion group were $306{\pm}24$ compared with $72{\pm}8$ in the sham operation group. In the TTC staining method, the cortical infarct affecting 34.8% of hemispheric volume were created in all of animals (n＝10) undergoing 90 minute MCAO with 24 hours reperfusion, but the infarcted area were not found in the other(sham operation and 90 minute MCAO with 4 hours reperfusion)groups. In the H & E stain, the brain tissue following 90 minute MCAO with 4 hours reperfusion revealed only a pyknosis of the nuclei with shrunken cytoplasm, but infiltrated leukocytes were not observed. After 24 hours of reperfusion, a many leukocytes were infiltrated within parenchyma and blood vessles. Conclusions : These findings demonstrate the feasiblity of continous in vivo monitoring of leukocyte adherence in cerebral venules and suggest that reperfusion induced leukocyte adherence to venular endothelium may contribute to tissue injury following focal cerebral ischemia.

• Journal of Korean Neurosurgical Society
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• v.50 no.3
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• pp.252-255
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• 2011

Authors report a case of a painless acute dissecting aneurysm of the descending aorta in a patient who presented with unexplained hypotension followed by simultaneous paraplegia and right arm monoparesis. To our knowledge, case like this has not been reported previously. Magnetic resonance imaging of the brain and spine revealed hemodynamic cerebral infarction and extensive cord ischemia, respectively. Computerized tomography angiography confirmed a dissecting aneurysm of the descending aorta. The cause of the brain infarction may not have been embolic, but hemodynamic one. Dissection-induced hypotension may have elicited cerebral perfusion insufficiency. The cause of cord ischemia may be embolic or hemodynamic. The dissected aorta was successfully replaced into an artificial patch graft. The arm monoparesis was improved, but the paraplegia was not improved. In rare cases of brain and/or spinal cord infarction caused by painless acute dissecting aneurysm of the aorta, accurate diagnosis is critical because careless thrombolytic therapy can result in life-threatening bleeding.

• The Journal of Korean Medicine
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• v.22 no.4
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• pp.142-150
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• 2001

Objectives : The purpose of this investigation is to evaluate and compare the effects of Sunghyangjunggi-san (SH) and Gwackhyangjunggi-san (GH) extracts on reperfusion following the MCA occlusion in rats. Methods : To evaluate the effect of Sunghyangjunggi-san (SH) and Gwackhyangjunggi-san (GH) extracts on reperfusion following the MCA occlusion, the volume of cerebral infarction and edema were measured and the change of the CA1 pyramidal neurons in the hippocampus were investigated by light microscopy. Results : 1. The infarction volume of the control group was 23.6%, that of the GH group was 23.7%, and that of the SH group was 18.5%. 2. The brain edema volume of the control group increased by 16% compared with that of the normal group, that of the GH group increased by 14%, and that of the SH group increased by 9%. 3. The number of surviving pyramidal neurons in the CAI area of the hippocampus was investigated under light microscopy. In the control group, few surviving pyramidal neurons excisted (mean 6.4) and similarly in the GH group (mean 8.5), but in the SH group, the number of surviving pyramidal neurons was significantly higher, to the mean 18.4. Conclusions : According to the above results, in regard to the damage of neurons following cerebral ischemia, the GH group has little effect of the protection of neurons compared to the control group, but the SH group has a remarkable effect.

• Biomolecules & Therapeutics
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• v.17 no.3
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• pp.270-275
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• 2009

Polyethylene glycol-conjugated hemoglobin (PEG-Hb) has been proposed as a blood substitute for transfusion due to their plasma expansion and oxygen transport capabilities. The protective effect of PEG-Hb on cerebral hypoxic-ischemic injury was investigated in neonatal hypoxia model and adult rat focal cerebral ischemia model. As intravenously administered 30 min before the onset of hypoxia, PEG-Hb markedly protected cerebral hypoxic injury in a neonatal rat hypoxia model. A similar treatment of PEG-Hb largely reduced the ischemic injury ensuing after 2-h middle cerebral artery occlusion followed by 22-h reperfusion. Consistently, neurological disorder was significantly improved by PEG-Hb. The results indicate that the pharmacological blockade of cerebral ischemic injury by using PEG-Hb may provide a useful strategy for the treatment of cerebral stroke.

• The Journal of Internal Korean Medicine
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• v.26 no.3
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• pp.596-604
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• 2005

Objectives : Geopungjeseub-tang(Gufengchushi-tang) has been used in oriental medicine for many centuries as a therapeutic agent for hemiplegia caused by deficiency of qi(氣虛) and damp phlegm(濕痰). This study was performed to evaluate effects of Geopungjeseub-tang extract(GJT) on hemodynamics[regional cerebral blood flow(rCBF), pial arterial diameter(PAD), mean arterial blood pressure(MABP), heart rate(HR)] in normal rats and in rats with cerebral ischemia by middle cerebral artery(MCA) occlusion. Also, effects of adrenergic ${\beta}-receptor$, cyclooxygenase on response to GJT were evaluated. Methods : Laser-doppler flowmetry(LDF) measured changes of rCBF, MABP and HR. Video microscope and width analyzer measured changes in PAD. Results : rCBF and PAD increased after treatment with GJT(10mg/kg, i.v.) during the period of cerebral reperfusion, and pretreatment with indomethacin raised rCBF and PAD increased after treatment with GJT during the same period as above. Pretreatment with propranolol decreased rCBF, but increased after GJT treatment, but raised PAD increased after GJT treatment during this period of reperfusion. Conclusion : CR caused diverse responses were observed in rCBF and PAD after treatment with GJT. ACF action is mediated by adrenergic ${\beta}-receptor$ and cyclooxygenase. Result suggest that GJT has an anti-ischemic effect through the improvement of cerebral hemodynamics and has theraputic potential for cerebral apoplexy.

• Journal of Korean Neurosurgical Society
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• v.59 no.6
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• pp.544-550
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• 2016

Objective : Cerebral endothelial cells have unique biological features and are fascinating candidate cells for stroke therapy. Methods : In order to understand the molecular mechanisms of human cerebral endothelial cell (hCMEC/D3) transplantation in a rat stroke model, we performed proteomic analysis using 2-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Protein expression was confirmed by quantitative real-time PCR and Western blot. Results : Several protein spots were identified by gel electrophoresis in the sham, cerebral ischemia (CI), and CI with hCMEC/D3 treatment cerebral ischemia with cell transplantation (CT) groups, and we identified 14 differentially expressed proteins in the CT group. Proteins involved in mitochondrial dysfunction (paraplegin matrix AAA peptidase subunit, SPG7), neuroinflammation (peroxiredoxin 6, PRDX6), and neuronal death (zinc finger protein 90, ZFP90) were markedly reduced in the CT group compared with the CI group. The expression of chloride intracellular channel 4 proteins involved in post-ischemic vasculogenesis was significantly decreased in the CI group but comparable to sham in the CT group. Conclusion : These results contribute to our understanding of the early phase processes that follow cerebral endothelial cell treatment in CI. Moreover, some of the identified proteins may present promising new targets for stroke therapy.

• Biomolecules & Therapeutics
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• v.25 no.3
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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.

• Journal of Veterinary Clinics
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• v.26 no.1
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• pp.104-108
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• 2009

Global cerebral ischemia occurs commonly in patients who have a variety of clinical conditions including cardiac arrest and shock. Cerebral ischemia results in a rapid depletion of energy stores that triggers resulting in excitotoxic death. Imaging studies of the brain with computed tomography(CT) or magnetic resonance imaging(MRI) are necessary to confirm the clinical neurolocalization, identify any associated mass effect, and rule out other causes of focal brain disorders. Cardiopulmonary arrest was occurred by propofol anesthesia in a 1 year old, intact female Beagle dog. After successful cardiopulmonary resuscitation was performed within 5 minutes, clinical signs such as vocalization, paddling, opisthotonus and seizure were represented. At the 12th day, CT and MRI examinations of the brain were performed to evaluate the brain. After euthanasia, histopathologic examination was performed. On transverse image of CT, lesions appeared as a hypodense in the right dorsal surface of the frontal lobe and level of optic canal, and dorsomedial surface of occipital lobe of cerebrum. No contrast enhancement was represented following intravenous contrast administration. On MR images of brain, the lesions were seen as a hyperintense on T2-weighted(T2W) images and a isointense or mild hypointense on T1-weighted(T1W) images. Hyperintense lesions both T2W and T1W images were observed at the surrounding cerebral sulcus. There was no significant signal changes on contrast T1WI. Histopathologic examination after euthanasia revealed that the lesion was necrosis of the cerebral cortex caused by cerebral ischemia.

• Advances in Traditional Medicine
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• v.8 no.4
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• pp.430-439
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• 2008

Chungpaesagan-tang (CPSGT) is most frequently used to treat ischemic brain injury in tradition Korean medicine. Clinically, cerebral ischemia is likely to be accompanied by preexisting or complicating disease. However, animal models used to examine the effects of herbal medicines on cerebral ischemia have not given this issue sufficient consideration. The present study was undertaken to determine the effects of CPSGT on focal cerebral ischemia in normal and SHR rats subjected to transient middle cerebral artery occlusion (MCAO). Animals were divided into four groups: Normal (Sprague-Dawley) rats subjected to MACO (the NC+MCAO group), normal rats subjected to MCAO and then administered CPSGT (NC + MCAO + CP), SHR rats subjected to MCAO (SHR + MCAO), and SHR rats subjected to MCAO and then administered CPSGT (SHR + MCAO + CP). MCAO was performed using the intraluminal method. CPSGT was administrated orally twice (1 and 4 h) after MCAO. All animals were sacrificed at 24 h postoperatively. Brain tissues were stained with hematoxylin & eosin, to examine the effect of CPSGT on ischemic brain tissues. In addition, changes in TNF-$\alpha$ expression in ischemic areas were examined by immunostaining. CPSGT was found to significantly reduce infarction areas in normal and SHR rats and infarction volumes in SHR rats. Similarly, CPGST markedly increased neuron numbers and sizes in all treated groups, except cell sizes in SHRs. Furthermore, CPSGT reduced TNF-$\alpha$ expression in MCAO administered SHR rats. The findings of the present study suggest that CPSGT effectively ameliorates neuron damage caused by MACO-induced cerebral ischemia, and that it has a significant neuroprotective effect after cerebral ischemia in SHR.