• 대한한의학회지
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• 제23권3호
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• pp.134-144
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• 2002

Objective : The purpose of this study was to investigate the effect of Jukryuk and Saengkang-juices on cerebral vascular ischemia (CVI) of the middle cerebral artery (MCA). Method : By admiuistration Jukryuk and Saengkang-juices, we compared treated groups with untreated groups, in view of five points as follows: 1) cerebral damage; 2) damaged area of ischemia; 3) cerebral edema; 4) the number of neuronal cells adjacent to the areas damaged by ischemia; and 5) the number of neuronal cells adjacent to the areas damaged by ischemia Results : In this experiment, the effect of Jukryuk and Saengkang-juices was determined by inducing cerebral vascular ischemia after occluding the middle cerebral artery (MCA) in mice, and making observations and comparisons such as alterations in damaged areas and neuronal cellular changes in the brain. Conclusions : According to the above results, Jukryuk and Saengkang-juices can protect the cerebral vascular ischemia.

• Archives of Pharmacal Research
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• 제25권5호
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• pp.697-703
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• 2002

We investigated that the role of nitric oxide (NO) on ischemic rats in brain and heart. Ischemia was induced by both common carotid arteries (CCA) occlusion for 24h following reperfusion. Then tissue samples were removed and measured NOx. In brain, NOx was increased by about 40% vs. normal and it was significantly inhibited by aminoguanidine, selective iNOS inhibitor. This result showed that NOx concentration was increased by iNOS. We investigated the role of $Ca^{2+}$ during ischemia. Nimodipine, L-type calcium channel blocker, didn't inhibit the increases of NOx concentration during ischemia. It suggested that increased NOx was due to calcium-independent NOS. MK-801, which N-methyl-D-aspartate (NMDA) receptor antagonist, didn't significantly prevent the increases of NOx. In heart, ischemia caused NOx decrease and it is inconsistent with NOx increase in brain. Aminoguanidine and nimodipine didnt affect on NOx decrease. But MK-801 more lowered NOx concentration than those of ischemia control group. It seemed that $Ca^{2+}$ influx in heart partially occurred via NMDA receptor and inhibited by NMDA receptor antagonist. The mean arterial pressure (MAP) in ischemic rats after 24h of CCA occlusion was decreased when compared to normal value, whereas the heart rates (HR) was not different between two groups. Aminoguanidine or MK801 had no effect on MAP or HR, but nimodipine reduced MAP. There was no difference the effects of aminoguanidine, nimodipine, or MK-801, on MAP and HR between normal rats and ischemic rats. In summary, ischemic model caused an increase of NOx concentration, suggesting that this may be produced via iNOS, which is calcium independent in brain. However in heart, ischemia decreased NOx concentration and NMDA receptor was partially involved. The basal MAP was decreased in ischemic rats but HR was not different from normal control, suggesting that increased NOx in brain of ischemic rat may result in the hypotension.

• Journal of Korean Neurosurgical Society
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• 제63권2호
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• pp.163-170
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• 2020

Objective : Milk fat globule-epidermal growth factor VIII (MFG-E8) may play a key role in inflammatory responses and has the potential to function as a neuroprotective agent for ameliorating brain injury in cerebral infarction. This study aimed to determine the role of MFG-E8 in brain injury in the subacute phase of cerebral ischemia in a rat model. Methods : Focal cerebral ischemia was induced in rats by occluding the middle cerebral artery with the modified intraluminal filament technique. Twenty-four hours after ischemia induction, rats were randomly assigned to two groups and treated with either recombinant human MFG-E8 or saline. Functional outcomes were assessed using the modified Neurological Severity Score (mNSS), and infarct volumes were evaluated using histology. Anti-inflammation, angiogenesis, and neurogenesis were assessed using immunohistochemistry with antibodies against ionized calcium-binding adapter molecule 1 (Iba-1), rat endothelial cell antigen-1 (RECA-1), and bromodeoxyuridine (BrdU)/doublecortin (DCX), respectively. Results : Our results showed that intravenous MFG-E8 treatment did not reduce the infarct volume; however, the mNSS test revealed that neurobehavioral deficits were significantly improved in the MFG-E8-treated group than in the vehicle group. Immunofluorescence staining revealed a significantly lower number of Iba-1-positive cells and higher number of RECA-1 in the periinfarcted brain region, and significantly higher numbers of BrdU- and DCX-positive cells in the subventricular zone in the MFG-E8-treated group than in the vehicle group. Conclusion : Our findings suggest that MFG-E8 improves neurological function by suppressing inflammation and enhancing angiogenesis and neuronal proliferation in the subacute phase of cerebral infarction.

• Journal of Korean Neurosurgical Society
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• 제50권3호
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• pp.173-178
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• 2011

Objective : The rat middle cerebral artery thread-occlusion model has been widely used to investigate the pathophysiological mechanisms of stroke and to develop therapeutic treatment. This study was conducted to analyze energy metabolism, apoptotic signal pathways, and genetic changes in the hippocampus of the ischemic rat brain. Methods : Focal transient cerebral ischemia was induced by obstructing the middle cerebral artery for two hours. After 24 hours, the induction of ischemia was confirmed by the measurement of infarct size using 2,3,5-triphenyltetrazolium chloride staining. A cDNA microarray assay was performed after isolating the hippocampus, and was used to examine changes in genetic expression patterns. Results : According to the cDNA microarray analysis, a total of 1,882 and 2,237 genes showed more than a 2-fold increase and more than a 2-fold decrease, respectively. When the genes were classified according to signal pathways, genes related with oxidative phosphorylation were found most frequently. There are several apoptotic genes that are known to be expressed during ischemic brain damage, including Akt2 and Tnfrsf1a. In this study, the expression of these genes was observed to increase by more than 2-fold. As energy metabolism related genes grew, ischemic brain damage was affected, and the expression of important genes related to apoptosis was increased/decreased.Conclusion : Our analysis revealed a significant change in the expression of energy metabolism related genes (Atp6v0d1, Atp5g2, etc.) in the hippocampus of the ischemic rat brain. Based on this data, we feel these genes have the potential to be target genes used for the development of therapeutic agents for ischemic stroke.

• 대한한의학회지
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• 제27권2호
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• pp.1-13
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• 2006

Objectives : Ischemic brain injury is a worldwide problem that often causes irreversible brain damage. Moreover, prevention of ischemic brain injury is more important than anything else, since after-effects of stroke significantly threat the quality of life. Jukryukjichul-hwan (JRH) is an oriental medicinal formula for stroke patients in Korea. This study evaluated neuroprotective effects of methanol extract of JRH on global cerebral ischemia in rats. Changes of the pyramidal neurons, Bax and TUNEL immuno-positive neurons in CA1 hippocampus were observed using immunohistochemistry. Methods : Sprague-Dawley Rats were induced with temporal global cerebral ischemia (TGI) by occluding the bilateral common carotid artery with hypotension, The rats were divided into 3 groups. We treated one group with methanol extract of JRH after operation, another group before and after the operation. We observed Bax expressions inducing apoptosis of neurons and TUNEL-positive Pyramidal Neurons as an index of survival and apoptosis of pyramidal neurons in CA1 Hippocampus. Results : JRH treatment before and after TGI inhibited Bax expression in CA1 hippocampus. JRH treatment before and after TGI reduced the cell death of pyramidal neurons in CA1 hippocampus. JRH treatment after TGI reduced the cell death of pyramidal neurons in CA1 hippocampus. JRH treatment before and after TGI reduced TUNEL-positive cells in CA1 hippocampus. Conclusion : These results suggest that JRH has a neuroprotective effect (by anti-apoptosis) against cerebral ischemia.

• 국제물리치료학회지
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• 제3권2호
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• pp.429-434
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• 2012

Ischemia, the leading cause of strokes, is known to be deeply related to synaptic plasticity and apoptosis in tissue damage due to ischemic conditions or trauma. The purpose of this study was to research the effects of NEES(needle electrode electrical stimulation) in brain cells of ischemia-induced rat, more specifically the effects of Poly[ADP-ribose] polymerase(PARP) on the corpus striatum. Ischemia was induced in SD mice by occluding the common carotid artery for 5 minutes, after which blood was re-perfused. NEES was applied to acupuncture points, at 12, 24, and 48 hours post-ischemia on the joksamri, and at 24 hours post-ischemia on the hapgok. Protein expression was investigated through PARP antibody immuno-reactive cells in the cerebral nerve cells and western blotting. The number of PARP reactive cells in the corpus striatum 24 hours post-ischemia was significantly(p<.05) smaller in the NEES group compared to the global ischemia(GI) group. PARP expression 24 hours post-ischemia was very significantly smaller in the NEES group compared to the GI group. Results show that ischemia increases PARP expression and stimulates necrosis, making it a leading cause of death of nerve cells. NEES can decrease protein expression related to cell death, protecting neurons and preventing neuronal apoptosis.

• 대한약리학회지
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• 제30권3호
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• pp.273-289
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• 1994

뇌-허혈후 나타나는 신경세포의 손상에 glutamate의 과다한 유리와 그의 N-methyl-D-aspartate (NMDA) 수용체: calcium 통로 활성작용 및 polyamine중 putrescine의 증가로 인한 신경세포내 $[Ca^{2+}]$의 상승과 관련 있다는 보고들이 있다. 본 연구에서는 Mongolian gerbil에서 5분간 경동맥을 차단하여 뇌-허혈을 가한후 재관류시 해마의 세포외액내 polyamine, glutamate, acetylcholine농도, 해마의 $[^3H]MK-801$ 결합능의 변동 및 해마조직소견의 변동에 미치는 비가역성 ornithine decarboxylase (ODC) 억제제인 difluoromethylornithine (DFMO), diamine oxidase (DAO) 억제제인 aminoguanidine (AG), NMDA 수용체 길항제인 MK-801 및 calcium 통로 차단제인 nimodipine (NM)의 효과를 비교-검색하였다. 해마 세포외액내 polyamine, glutamate 및 acetylcholine은 microdialysis probe를 해마의 CA1부위에 위치시킨 후 나온 분취액을 HPLC와 luminometer를 사용하여 측정하였고, 해마조직에서 신경세포의 손상은 cresyl-violet 염색법으로 관찰하였다. 허혈후 해마 세포외액내 putrescine농도는 5분이내에 급속히 증가하여 뇌-허혈후 96시간까지 증가되는 경향을 보였으며 AG과 MK-801 처치시 saline 처치군에 비하여 증가정도가 상승되었으나 NM과 DFMO 처치로 putrescine의 증가는 감소되는 경향을 보였다. 해마 세포외액내 glutamate의 농도는 허혈후 5분 이내에 9배이상 유의하게 증가한 후 급격히 감소되어 25분후에는 정상치로 회복되었으나, 이같은 변동은 AG, DFMO 및 MK-801 처치로 영향을 받지 않았고 NM 처치로는 glutamate의 증가가 둔화되는 경향을 보였다. 해마 세포외액내 acetylcholine 농도는 허혈에 의하여 큰변동이 없었으나 허혈전 acetylcholine농도는 DFMO나 MK-801처치로 감소되는 경향을 보였다. 해마-synaptosome막의 $[^3H]MK-801$ 결합능은 saline 처치군에 비하여 AG과 MK-801 처치로 유의하게 감소되었다. 해마의 조직소견상 AG과 NM은 허혈후의 신경세포손상을 억제하고, MK-801은 손상의 예방에 별 영향을 주지 못하였으나 DFMO는 허혈에 의한 신경세포의 손상을 더욱 악화시키는 경향을 보였다. 이상의 결과로 미루어 NM과 다른기전으로 AG은 해마신경세포의 손상을 NMDA-수용체: calcium 통로의 활성화를 조절하여 허혈성 뇌손상을 억제할 수 있으리라 사료된다.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.148.1-148.1
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• 2003

The effects of methanolic extracts of Polygalae Radix (PR 100mg/kg) was tested to evaluate on the neuroprotective activity (92％ p<0.001) on global cerebral schemia. Based on bioassays guided fractionation, butanol soluble fraction (BtOH 25mg/kg) had the neuroprotive effect (87％ p<0.001) of global cerebral ischemia in rat. Oxygen free radical injury plays an important role in neuronal damage induced by brain ischemia and reperfusion. (omitted)

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.304.1-304.1
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• 2002

Brain injury resulting from cerebral ischemia remains a major public health problem. Aloesin. main component of aloe possesses various biological activities such as wound healing, anti-gastric ulcer, and chemopreventive activity. In this study we investigated whether treatment with aloes in could protect brain injury induced by permanent focal cerebral ischemia in rats. We also compared aloes in with other neuroprotective. drugs such as MK801 and ebselen. (omitted)

• 대한본초학회지
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• 제27권6호
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• pp.83-90
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• 2012

Objectives : Modified Bo-Yang-Hwan-O-Tang (mBHT) is a polyherbal medicine of twelve herbs traditionally used in the treatment of cerebral and cardiac stroke and vascular dementia. The purpose of this study was to evaluate the neuroprotective effect, pyramidal neuronal cell, inflammation and apoptosis of mBHT against global ischemia in rats. Methods : Global ischemia was produced by two-vessel occlusion(2-VO) in SD male rats. mBHT at dose of 500 mg/kg was orally administrated for 2 weeks or 6 weeks after global ischemia. The histopathological changes of ischemic brain were observed by staining of hematoxylin and eosin (H&E) and Nissl and immunohistochemisty with anti-GFAP (glial fibrillary acidic protein) antibody as a astrocyte marker. The expression of inducible nitric oxide synthase (iNOS) and apoptotic proteins such as Bax, Bcl-2 and caspase-3 was determined by western blot. Results : mBHT treatment significantly inhibited the pyramidal neuronal loss in CA1 of hippocampus of global ischemic rats by 2-VO. mBHT also suppressed the activation of astrocytes in the CA1 at 6 weeks after ischemia. In addition, mBHT significantly increased the expression of anti-apoptotic protein, Bcl-2 on iscemic brain, and significantly attenuated the expression of apoptotic proteins, Bax and caspase-3. Conclusions : These results indicate that mBHT inhibits neuronal cell damage induced in global ischemia by 2-VO, suggesting that mBHT may be a potential candidate for the treatment of vascular dementia.