• 대한자기공명의과학회:학술대회논문집
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• 대한자기공명의과학회 2000년도 제5차 추계학술대회
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• pp.15-15
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• 2000

• The Korean Journal of Physiology and Pharmacology
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• 제28권3호
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• pp.239-252
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• 2024

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 ㎍/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 ㎍/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

• 한국한의학연구원논문집
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• 제6권1호
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• pp.89-98
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• 2000

Cerebral ischemia, the most prevalent form of clinical stroke, is a medical problem of the first magnitude. Substantial efforts are being made to develop drugs which will protect the brain from the neurodegeneration followed by an ischemic stroke. A key factor in this process is the development of animal models that mimic the neuropathological consequences of stroke. Recently, there is increasing an evidence that free radical is involved in the mechanisms of ischemic brain damage. We investigated the macro scale gene expression analysis on the global ischemia induced by 4-vessel occlusion in Wister rats. The recent availability of microarrays provides an attractive strategy for elaborating an unbiased molecular profile of large number of genes during ischemic injury. This experimental approach offers the potential to identify molecules or cellular pathways not previously associated with ischemia. Ischemia was induced by 4-vessel occlusion for 10 minutes and reperfused again. RNA from sham control brain and time-dependent ischemed brain were hybridized to microarrays containing 4,000 rat genes. 589 genes were found to be at least 2 fold regulated at one or more time points. These survey data provide the foundation studies that should provide convincing proof for ischemia and oxidative stress on gene expression.

• 대한본초학회지
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• 제27권2호
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• pp.61-67
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• 2012

Objective : Angelica Gigas Nakai is a popular oriental medicine used for the treatment of vascular diseases. The aim of this study is to investigate neuroprotective effect of the water extract of Anelicae Gigantis Radix Palva (AG) in transient middle cerebral artery occlusion (tMCAO)-induced ischemic rats via the regulation of angiogenesis-related molecules. Methods : Sprague-Dawley rats were intraperitoneally administrated with AG water extract at doses of 10, 25, 50 mg/kg body weight after tMCAO (90 min occlusion). reperfusion for 24 hr infarction volumes were measured by 2,3,5-tetrazolium chloride (TTC) staining. Brain tissues were observed neuronal cell injuries by nissl staining, and also brain-blood barrier (BBB) permeability change by evans blue. Expression of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and Tie-2 receptor protein in brain tissues was determined by western blot. Results : AG water extract significantly reduced infarction volume in ischemic brains of rats, degradation of neuronal cell, BBB permeability and expression of VEGF protein dose-dependently. Ang-1 protein was increased dose-dependantly, not significantly. Conclusion : This study suggests that AG water extract shows neuroprotective effect by preventing BBB breakdown, with regulating angiogenesis factor VEGF and Ang-1.

• Biomolecules & Therapeutics
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• 제15권3호
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• pp.169-174
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• 2007

In the present study, we investigated the neuroprotective effects of standardized Ginkgo biloba extract (GBB) (total terpene trilactones, 13 ${\pm}$ 3%; biflavone, 4.5 ${\pm}$ 1.5%; flavonol glycoside, < 8%; proanthocyanidine, under detection limit) on ischemia-reperfusion-induced brain injury in the rats. Ischemia was induced by the intraluminal occlusion of the right middle cerebral artery for 2 h and reperfusion was continued for 22 h. GBB was orally administered, promptly prior to reperfusion and 2 h after. Total infarction volume in the ipsilateral hemispheres of ischemia-reperfusion rats were significantly reduced by treatment with GBB in a dose-dependent manner (P<0.05). The therapeutic time window of GBB was 3 h in this ischemia-reperfusion rat model. Furthermore, GBB also significantly inhibited increased neutrophil infiltration of ischemic brain tissue, as estimated by myeloperoxidase activity. These findings suggest that GBB plays a crucial protective role in ischemia-induced brain injury, in part, via inhibition of neutrophil infiltration, and suggest that this GBB could serve as a neuroprotective agent following transient focal ischemic brain injury.

• Preventive Nutrition and Food Science
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• 제16권3호
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• pp.217-223
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• 2011

Ischemic stroke constitutes about 80% of all stroke incidences. It is characterized by brain cell death in a region where cerebral arteries supplying blood are occluded. Under these ischemic conditions, apoptosis is responsible for the cell death, at least in part. Goat's-beard (Aruncus dioicus var. kamtschaticus) is a perennial plant that grows naturally in the alpine regions of Korea. In the present study, we first determined whether water extract of goat's-beard (HY1646) and some of its fractions prepared by partitioning with organic solvents could improve the viability of human hepatocellular carcinoma cells (HepG2) cultured under hypoxic condition by blocking apoptotic pathways. Based on the in vitro findings, we subsequently investigated whether HY1646 and the ethyl acetate fraction (EA) selected from cell culture-based screening could attenuate brain injury in a rat middle cerebral artery occlusion (MCAO) model of ischemia (2 hr), followed by 22 hours of reperfusion. The cell number was sustained close to that initially plated in the presence of HY1646 even after 24 hr of cell culture under hypoxic condition (3% $O_2$), at which time the cell number reached almost zero in the absence of HY1646. This improvement in cell viability was attributed to the delay in apoptosis, identified by the formation of DNA ladder in gel electrophoresis. Of fractions soluble in hexane, ethyl acetate (EA) and butanol, EA was chosen for the animal experiments because EA demonstrated the best cell viability at the lowest concentration (10 ${\mu}g$/mL). HY1646 (200 mg/kg) and EA (10 and 20 mg/kg) significantly reduced infarct size, an index of brain injury, by 16.6, 40.0 and 61.0%, respectively, as assessed by 2,3,5-triphenyl tetrazolium chloride staining. The findings suggest that prophylactic intake of goat's beard might be beneficial for preventing ischemic stroke.

• 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.

• 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.

• 동의신경정신과학회지
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• 제17권2호
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• pp.61-73
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• 2006

Objective : This study was to investigate the effects of Banhabaekchulchunma-Tang(BCT) on Dementia induced by focal ischemic injury in the rats. Method : Experimental groups were divided into 4 groups ; Normal group, Control group, BCT1 group and BCT2 group. Control group were no treated after focal brain ischemic injury. BCT1 group were administered BCT 0.3 ml/kg to focal brain ischemic injuried rats for 21 days, BCT2 group were administered BCT 1.2 ml/kg to focal brain ischemic injuried rats for 21 days. The present author observed the number of errors on the eight-arm radial maze task , the rate of correct choice on the eight-arm radial maze task, the values of density of Cresyl Violet-stained sections in the hippocampal CA1 and the values of density of Acetlycholin Esterase(AchE) stained nuclei in the hippocampal CA1. Result : 1. The number of errors in the eight-arm radial maze task was significantly decreased in BCT1 group on 1-6th days. And it was significantly decreased in BCT2 group on 1st, 2nd, 3rd and 6th day compared with control group. 2. The rate of correct choice on the eight-arm radial maze task was increased in BCT1 group and BCT2 group compared with control group, but the value was not significant. 3. The values of density of Cresyl Violet-stained sections in the hippocampal CA1 were significantly increased in BCT1 group and BCT2 group compared with control group. 4. The values of density of AchE stained nuclei in the hippocampal CA1 were significantly increased in BCT1 group compared with control group. Conclusion : The present author thought that Banhabaekchulchunma-Tang could be used to cure dementia derived by the phlegm retention of fluid.

• 대한한의학회지
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• 제25권3호
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• pp.32-44
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• 2004

Objectives : This study was undertaken to prove the effect of GSHT on the glutamate receptor, free radical and brain damage in rats subjected to brain ischemia Methods : Levels of cultured cortical neuron death caused by toxic chemicals were measured by LDH release assay. Neuroprotective effects of GSHT on brain tissues were examined in vivo by ischemic model of middle cerebral artery (MCA) occlusion. Results : GSHT showed significant inhibitory effect on LDH release induced by NMDA-kinate-Fe/sup 2+/. GSHT remarkably decreased coma duration time in a nonfatal dose of KCN and showed higher survival rate in a fatal dose. GSHT remarkably decreased ischemic area and edema induced by the MCA blood flow block. GSHT showed high improvement of forelimb and hind limb test after MCA occlusion in neurological examination. GSHT showed no significant change after MCA occlusion in pathological observation of the normal group. Conclusions : These results indicate that GSHT can be used to treat the brain damage caused by brain ischemia. Further study will be needed about the functional mechanism, etc.