• 동의생리병리학회지
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• 제19권1호
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• pp.246-253
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• 2005

This study was designed to investigate the neuroprotective effects of Guh-Poong-Chung-Sim-Hwan(GCH) on ischemia induced by middle cerebral artery occlusion(MCAO) in Sprague-Dawley rats. The effects of GCH administration on the size of the brain infarct and the functional status of the rats after ischemia were examined, as well as the expression of COX-2 in acute phase. The recovery of motor functions for 7 days and the brain infarct were examined to find out the delayed effects of daily GCH-administration as well. In conclusion, we found that GCH reduced both functional deficits and brain damage in the MCAO rat model of stroke. In addition, high doses of GCH reduced COX-2 expression in the penumbra. It is well known that herbal medication including GCH is very safe for humans. Accordingly, our results support the clinical use of this GKM for the treatment of stroke and offer the possibility that a potent neuroprotective agent could be developed from Korean herbal medicines.

• Journal of Acupuncture Research
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• 제34권3호
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• pp.1-11
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• 2017

Objectives : The purpose of this study was to examine the effects of Acori Graminie Rhizoma Pharmacopuncture (PA-AG) at GV20 on cerebral ischemia-induced dementia in Mice. Methods : Mice were divided into the five following groups: normal, control, acupuncture, PA-AG (17 mg/kg), and PA-AG (34 mg/kg). All groups, except the normal group, had cerebral ischemia induced by occlusion of middle cerebral artery. The control group was not treated. The acupuncture, PA-AG (17 mg/kg), and PA-GA (34 mg/kg) groups were treated every other day with a total of 6 treatments. The effect of treatment was observed by Bax, Bcl-2, Bax/Bcl-2 ratio, cytochrome c, cresyl violet, and choline acetyltransferase staining. Results : In the PA-AG (34 mg/kg) group, the intensity of Bax was decreased and the intensity of Bcl-2 was increased. The Bax/Bcl-2 ratio also decreased in the PA-AG (34 mg/kg) group. The intensity of cytochrome c protein stain was decreased in the PA-AG (17 mg/kg) group. The density of neurons stained by cresyl violet and choline acetyltransferase (ChAT) was increased in the AT, PA-AG (17 mg/kg), and PA-AG (34 mg/kg) groups when compared with that of the control group. Conclusion : PA-AG at GV20 was effective on cerebral ischemia-induced dementia in mice.

• Journal of Korean Neurosurgical Society
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• 제55권6호
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• pp.307-312
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• 2014

Objective : We investigated the expression of hippocampal heat shock protein 70 (HSP-70) infarction volume after different durations of experimental ischemic stroke in mice. Methods : Focal cerebral ischemia was induced in mice by occluding the middle cerebral artery with the modified intraluminal filament technique. Twenty-four hours after ischemia induction, both hippocampi were extracted for HSP-70 protein analyses. Slices from each hemisphere were stained with 2,3,5-triphenyltetrazolium chloride (2%), and infarction volumes were calculated. HSP-70 levels were evaluated using western blot and enzyme-linked immunosorbent assay (ELISA). HSP-70 subtype (hsp70.1, hspa1a, hspa1b) mRNA levels in the hippocampus were measured using reverse transcription-polymerase chain reaction (RT-PCR). Results : Cerebral infarctions were found ipsilateral to the occlusion in 10 mice exposed to transient ischemia (5 each in the 30-min and 60-min occlusion groups), whereas no focal infarctions were noted in any of the sham mice. The average infarct volumes of the 2 ischemic groups were $22.28{\pm}7.31mm^3$ [30-min group${\times}$standard deviation (SD)] and $38.06{\pm}9.53mm^3$ (60-min group${\times}$SD). Western blot analyses and ELISA showed that HSP-70 in hippocampal tissues increased in the infarction groups than in the sham group. However, differences in HSP-70 levels between the 2 infarction groups were statistically insignificant. Moreover, RT-PCR results demonstrated no relationship between the mRNA expression of HSP-70 subtypes and occlusion time or infarction volume. Conclusion : Our results indicated no significant difference in HSP-70 expression between the 30- and 60-min occlusion groups despite the statistical difference in infarction volumes. Furthermore, HSP-70 subtype mRNA expression was independent of both occlusion duration and cerebral infarction volume.

• Reproductive and Developmental Biology
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• 제35권2호
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• pp.167-174
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• 2011

Acute ischemic stroke results from sudden decrease or loss of blood supply to an area of the brain, resulting in a coinciding loss of neurological function. The antioxidant action of melatonin is an important mechanism among its known effects to protective activity during ischemic/reperfusion injury. The focus of this research, therapeutic efficacy of melatonin on recovery of neurological function following long term treatment in ischemic brain injured rats. Male Sprague-Dawley rats (n=40; 8 weeks old) were divided into the control group, and MCAo groups (Vehicle, MT7 : MCAo+ melatonin injection at 7:00, MT19 : MCAo+melatonin injection at 19:00, and MT7,19 : MCAo+melatonin injection at 7:00 and 19:00). Rat body weight and neurological function were measured every week for 8 weeks. After 8 weeks, the rats were anesthetized with a mixture of zoletil (40 mg/kg) and xylazine (10 mg/kg) and sacrificed for further analysis. Tissues were then collected for RNA isolation from brain tissue. Also, brain tissues were analyzed by histological procedures. We elucidated that melatonin was not toxic in vital organs. MT7,19 was the most rapidly got back to mild symptom on test of neurological parameter. Also, exogenous melatonin induces both the down-regulation of detrimental genes, such as NOSs and the up-regulation of beneficial gene, including BDNF during long term administration after focal cerebral ischemia. Melatonin treatment reduced the loss of primary motor cortex. Therefore, we suggest that melatonin could be act as prophylactic as well as therapeutic agent for neurorehabilitative intervention.

• 동의생리병리학회지
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• 제21권5호
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• pp.1250-1259
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• 2007

Bambusae Caulis in Liquamen(BCL) has been commonly prescribed for stroke patients in the traditional Oriental medicine. So this study is aims to investigate the anti-apoptotic and neuroprotective effects of Bambusae Caulis in Liquamen(BCL) manufactured by different production process on the focal ischemia induced by intraluminal filament insertion in rats. The focal ischemia was induced by intraluminal filament insertion into middle cerebral artery. The animals were divided into four groups (n=15 in each group). The ischemia induced and not treated group : Control group, the ischemia induced and oral medication of the three kinds of BCL : BCL-A group, BCL-B group, BCL-C group. BCL-A was produced by heating at a low temperature$(250^{\circ} C)$ in electric kiln and filtering. BCL-B was produced by heating at a high temperature$(900^{\circ} C{\sim}1,000^{\circ}C)$ in yellow earth kiln and refining and filtering. BCL-C was produced by heating at a low temperature$(400^{\circ} C)$ yellow earth kiln and no refining and filtering. The anti-apoptotic and neuroprotective effects of the oral medication of BCL were observed by Bax, BCL-2, cytochrome c, mGluR5, cresyl violet and ChAT-stain. Our study suggests that BCl-A(was produced by heating at a low temperature in electric kiln and filtering) and BCL-C(was produced by heating at a low temperature in yellow earth kiln and no refining and filtering) show anti-apoptotic and neuroprotective effects on the focal ischemia induced by intraluminal filament insertion in rats and BCL-C is more effective than BCL-A.

• Archives of Pharmacal Research
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• 제23권4호
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• pp.413-417
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• 2000

The effect of ischemia/reperfusion-induced neuronal damage on the memory impairment were investigated using active avoidance and Morris water maze tasks in Wistar rats. Focal ischemia was induced by 1 h occlusion of the right middle cerebral artery (MCA) of Wistar male rats. Reperfusion was induced by releasing the occlusion and restoring the blood circulation for 24 h. The acquisition and preservation memory tested by active avoidance showed a significant difference between the sham and ischemia/reperfusion group. The water maze acquisition performance was also significant difference between sham and ischemia/repefusion groups in both latency and moving distance. The infarction volume was increased by the ischemia/reperfusion. Furthermore, the cresyl violet staining of the ischemia/reperfusion brain showed severe neuronal damage (pyramidal cell loss) in the cortex in addition to the striatum lesion of brain. This study shows that pyramidal cell damage in the cortex lesion may be partially related to memorial disturbance in the ischemia/reperfusion brain injury.

• The Korean Journal of Physiology and Pharmacology
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• 제22권2호
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• pp.145-153
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• 2018

The subgranular zone (SGZ) of hippocampal dentate gyrus (HDG) is a primary site of adult neurogenesis. Toll-like receptors (TLRs), are involved in neural system development of Drosophila and innate immune response of mammals. TLR2 is expressed abundantly in neurogenic niches such as adult mammalian hippocampus. It regulates adult hippocampal neurogenesis. However, the role of TLR2 in adult neurogenesis is not well studied in global or focal cerebral ischemia. Therefore, this study aimed to investigate the role of TLR2 in adult neurogenesis after photochemically induced cerebral ischemia. At 7 days after photothrombotic ischemic injury, the number of bromodeoxyuridine (BrdU)-positive cells was increased in both TLR2 knock-out (KO) mice and wild-type (WT) mice. However, the increment rate of BrdU-positive cells was lower in TLR2 KO mice compared to that in WT mice. The number of doublecortin (DCX) and neuronal nuclei (NeuN)-positive cells in HDG was decreased after photothrombotic ischemia in TLR2 KO mice compared to that in WT mice. The survival rate of cells in HDG was decreased in TLR2 KO mice compared to that in WT mice. In contrast, the number of cleaved-caspase 3 (apoptotic marker) and the number of GFAP (glia marker)/BrdU double-positive cells in TLR2 KO mice were higher than that in WT mice. These results suggest that TLR2 can promote adult neurogenesis from neural stem cell of hippocampal dentate gyrus through increasing proliferation, differentiation, and survival from neural stem cells after ischemic injury of the brain.

• 한국전문물리치료학회지
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• 제12권3호
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• pp.11-21
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• 2005

The present study was aimed at investigating the effect of swimming training on brain function after focal cerebral ischemia in rats. Therefore, this study was examined on neurogenesis in dentate gyrus of hippocampus using 5-bromo-2'-deoxyuridine (BrdU) to label proliferating cells and assessed the neurological response following focal cerebral ischemia in rats using neurological motor behavioral test. In an observer-blinded fashion, twenty male Sprague-Dawley (280~310 g, 7 weeks old) rats were divided into four groups: MCAO plus swimming group (ME, $n_1$=5), MCAO plus control group (MC, $n_2$=5), SHAM plus swimming group (SE, $n_3$=5), SHAM plus control group (SC, $n_4$=5). The results of this study were as follows: 1) The limb placing time before and after swimming in the ME group were significantly longer than the MC group (p<.05), the SE group were significantly longer than the SC group (p<.01). 2) The balance beam scores before and after swimming in the ME group was higher than the SE group, the MC group was higher than the SC group but was not significantly different (p>.001). 3) The foot fault index before and after swimming training in ME group was significantly lower (i.e., improved) than the MC group (p<.001) and the SE group (p<.001), the SE group was significantly lower (i.e., improved) than the SC group (p<.001). 4) The mean number of BrdU-positive cells in the dentate gyrus in the ME group was significantly higher than the MC group (p<.001) and the SE group (p<.01). The MC group and the SE group was significantly higher than the SC group (p<.001). 5) There was significantly correlation between limb placing time and number of BrdU-positive cells on swimming training, there was positive correlation (r=.807, p<.0001) and between foot fault index and BrdU-positive cells number, there was negative correlation (r=-.503, p<.05). However, between balance beam scores and BrdU-positive cells number, there was no correlation. In conclusion, the present study demonstrates that the role of swimming training improves behavioral motor function probably by enhancing cell proliferation in that hippocampus. This study provides a model for investigating the stroke rehabilitation that underlies neurogenesis and functional ability.

• 대한핵의학회지
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• 제29권3호
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• pp.294-306
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• 1995

국소뇌허혈에서 MK-801의 신경세포방어효과를 검토하기 위하여 흰쥐의 중뇌동맥을 폐색시켜 뇌허혈 및 경색을 유발하기 전과 후에 MK-801을 투여한 후 국소뇌포도당이용률의 변화를 2-deoxy-D-(14C)glu-cose 자가방사기록법을 이용하여 측정하고 이를 대조군과 비교하였다. 중대뇌동맥폐색 시술 전과 후에 평균동맥압, 직장체온, 동맥혈 PH, $pCO_2,\;pO_2$의 유의한 차이는 없었다. [$^{14}C$]DG 실험 중 대조군, MK-801 전처처군과 MK-801 후처치군 사이에서 평균동맥압, 직장 체온, 동맥혈장 당농도, 동맥혈 pH, $pCO_2,\;pO_2$의 유의한 차이는 없었다. 대조군에서 중대뇌동맥폐색 24시간 후에 폐색된 대뇌반구의 전두엽피질, 두정엽피질, 담창구, 편도, 해마 CA-2 지역, CA-3 지역, 내비회, 후두엽피질, 측두엽피질의 국소뇌포도당이용률은 반대쪽정상 대뇌반구 상동부위의 국소뇌포도당이용률보다 유의하게 낮았다. MK-801 전처치군에서 전두엽피질, 두정엽피질, 편도, 해마 CA-2 지역, 내비회, 후두엽피질, 측두엽피질의 병변/정상 국소뇌포도당이용률 비는 대조군의 그것보다 유의하게 높았다. 한편 MK-801 후처치군에서는 전두엽피질, 두정엽피질, 해마 CA-2 지역, 후두엽피질, 측두엽피질의 병변/정상 국소뇌포도 당이용률 비가 대조관의 그것보다 유의하게 높았다. MK-801 전처치군 정상 대뇌반구의 미상핵-피각, 전두엽피질, 두정엽피질, 대상회전, 담창구, 시상, 뇌량, 해마 CA-1, CA-2, CA-3 지역, 후두엽피질, 측두엽피질의 국소뇌포도당이용률은 대조군 정상 대뇌반구의 그것보다 유의하게 높았다. 반면 MK-801 후처치군 정상 대뇌반구의 국소뇌포도당이용률은 대조군 정상대뇌반구의 국소뇌포도당이용률과 유의한 차이가 없었다. 뿐만 아니라 폐색된 대뇌반구에서도 정상 대뇌반구와 매우 유사한 결과를 보였다. 즉, MK-801 전처치군에서는 미상핵-피각, 전두엽피질, 두정엽피질, 대상회전, 담창구, 시상, 뇌량, 해마 CA-1, CA-2, CA-3 지역, 내비회, 후두엽피질, 측두엽피질의 국소뇌포도당이용률이 대조군보다 유의하게 높은 반면, MK-801 후처치군에서는 대조군과 유의한 국소뇌포도당이용률의 차이를 나타내지 않았다. 이상의 결과로부터 국소뇌허혈에서 MK-801은 신경세포방어효과를 나타낼 것으로 생각된다. MK-801은 뇌포도당이용률을 국소적으로 증가시키며, 이는 NMDA 수용체 길항제 투여와 뇌기능 변화의 유관성을 시사하는 것이다.

• Journal of Korean Biological Nursing Science
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• 제3권1호
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• pp.41-52
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• 2001

This study was undertaken to investigate the effects of n-6(corn oil) & n-3(fish oil) fatty acids on infarction size and the cerebral activities of antioxidant enzyme in rat focal brain ischemia model. Weaning Sprague-Dawley rats were fed with either corn oil supplemented diet(COD, 14% corn oil) or fish oil supplemented diet(FOD, 14% menhaden oil) for 6 weeks. The right middle cerebral artery was occluded for 2 hours with a silicon rubber coated nylon surgical thread. After 24 hours of recirculation, the rats were sacrificed and brain sections were photographed using CCD camera after staining with 2, 3, 5-triphenyltetrazolium chloride for 60 minutes in room temperature. The infarcted area was measured and the volume of infarction was calculated. Catalase(CAT), superoxide dismutase(SOD) activities, and fatty acid composition in the brain were also measured. The total and corrected infarction volumes were not significantly different between FOD and COD group. The docosagexaenoic acid(DHA) and DHA content/arachidonic acid(AA) ratio of the cerebral cortex, an index of defense against lipid oxidation, were significantly increased in FOD group compared to those of COD group(p<0.05). In the left cortex(non-infarction side) as well as the right cortex(infarction side) of FOD group, CAT and Cu/Zn SOD activities were higher than those of the COD group(p<0.05). However, CAT and Cu/Zn SOD activities were not significantly different between the left cortex(non-infarction side) and the right cortex(infarction side) of both FOD and COD group. GPx activities were also not significantly different between two groups. Our results demonstrate that the brain infarction size in FOD and COD were not significantly different. However, cerebral lipid composition and antioxidant enzyme activities in FOD and COD group were different. Fish oil, a source of n-3 polyunsaturated fatty acid(PUFA) and corn oil, that of n-6(PUFA) may have a protective effect against oxidative stress induced via different mechanisms.