• The Journal of Korean Medicine
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• v.27 no.2 s.66
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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.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.3
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• pp.257-263
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• 2009

This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1 ${\alpha}$ (HIF-1 ${\alpha}$) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1 ${\alpha}$ proteins expression, thereby providing a benefit in therapy of cerebral ischemia.

• Journal of Korean Neurosurgical Society
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• v.41 no.5
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• pp.306-313
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• 2007

Objective : In permanent distal middle cerebral artery occlusion [pdMCAO] model of rats, the temporal order of subcellular translocation is not fully understood yet. We studied translocation sequence of cytochrome c and apoptosis inducing factor [AIF] after pdMCAO and patterns of expression. Methods : Twenty-one male rats - with ten minutes, 1, 4, 8, 24 and 48 hours of pdMCAO groups - were enrolled. At core and penumbra area of each cerebral cortex, Western blotting of cytochrome c and AIF were performed using cytosolic fractions and then compared with sham specimens. With 48 hours group, the expression of cytochrome c and AIF was examined with immunofluorescent staining. Results : Compared to sham, the cytosolic translocation of cytochrome c significantly increased at all time points [p<0.05]. As early as 10 min after onset of ischemia, it was increased significantly [p<0.01]. The cytosolic translocation of AIF showed gradual increase with the passage of time and significantly increased 8 hours after [p<0.05]. As late as 24 hours and 48 hours after onset of ischemia, there were increased most significantly [p<0.01]. At penumbra, both proteins failed to show significant increase at all time points. At 48 hours after ischemia, colocalization of cytochrome c and AIF were confirmed. Conclusion : Cytosolic translocation of cytochrome c peaks much earlier than that of AIF in pdMCAO model of rat. Caspase dependent apoptosis activates soon after ischemia and later, it can be reinforced by gradually increasing AIF in ischemic core.

• Journal of Korean Biological Nursing Science
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• v.4 no.2
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• pp.19-40
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• 2002

The purpose of this study was to determine the effect of DHEA on Type I(soleus) and II muscles(plantaris, gastrocnemius) in a focal brain ischemia model rat. Thirty-seven male Sprague-Dawley rats with $200{\sim}250g$ body weights were randomly divided into four groups : CINS(cerebral ischemia + normal saline), CIDH(cerebral ischemia + DHEA), SHNS(sham + normal saline), SHDH (sham + DHEA). Both the CINS and CIDH groups were undergone a transient right middle cerebral artery occlusion operation. In the SHNS and SHDH groups, a sham operation was done. DHEA was administered daily at a dose of 0.34mmol/kg, and normal saline was administered daily at the same dose by intraperitoneal injection for 7days after operation. Cerebral infarction in the CINS and CIDH groups was identified by staining with 2% triphenyltetrazolium chloride solution for 60 minutes. The data were analyzed by Kruskal-Wallis test and Mann-Whitney U test using the SPSSWIN 9.0 program. The results were summarized as follows: 1) The muscle weights of soleus(Type I), plantaris and gastrocnemius(Type II) in CINS group were significantly less than those of the SHNS group(p<.01). The muscle fiber cross-sectional area of the CINS group was significantly less than that of the SHNS group in Type I muscle fiber of the soleus and Type II muscle fiber of the plantaris and gastrocnemius(p<.05). The myofibrillar protein content of the CINS group was significantly less than that of the SHNS group in the left gastrocnemius and right soleus(p<.05). 2) The muscle weights of the soleus, plantaris and gastrocnemius except the unaffected side of the plantaris in the CIDH significantly increased compared to those of the CINS group(p<.05). The muscle fiber cross-sectional area of the CIDH group significantly increased compared to that of the CINS group in Type II muscle fiber of the plantaris and gastrocnemius(p<.05). The myofibrillar protein content of the CIDH group significantly increased compared to that of the CINS group in the left soleus(p<.05). 3) On the post-op 8 day, the body weight of the CINS group was significantly less than that of the CIDH, SHNS and SHDH groups(p<.01). Total diet intake of the CINS and CIDH groups was significantly less than that of the SHNS and SHDH groups(p<.01). Based on these results, it was identified that muscle atrophy could be induced during the 7 days after cerebral infarction, and DHEA administration during the early stage of cerebral infarction might attenuate muscle atrophy.

• Natural Product Sciences
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• v.15 no.4
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• pp.198-202
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• 2009

Based on the use of Acorus gramineus SOLAND (AG) for the treatment of stroke in traditional Korean medicine, the present study was carried out to evaluate neuroprotective effects of ${\alpha}$-asarone after transient global cerebral ischemia using rat 4-vessel occlusion (4VO) model in rats. ${\alpha}$-Asarone (5 mg/kg) administered intraperitoneally significantly protected CA1 neurons against 10 min transient forebrain ischemia as demonstrated by measuring the density of neuronal cells stained with Cresyl violet. ${\alpha}$-Asarone significantly reduced hippocampal neuronal cell death by 85.2% where as its isolated single compounds from AG compared with a vehicle-treated group.

• Biomolecules & Therapeutics
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• v.8 no.3
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• pp.255-261
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• 2000

WooHwangChungSimWon is a traditional prescription for treating with hypertension, arteriosclerosis, coma, and stroke in China, Korea, and Japan. In the new presciption of WooHwangChungSimWon, the covet is substituted for the musk, the major component of WooHwangChungSimwon, because of the prohibition law about the musk. We have made a comparative study of the effects on the ischemic damage between the musk containing and civet containing WooHwangChungSimWon. In order to investigate the effects of WooHwangChungSimWon on the ischemic damage, each samples were administrated for 12 days, ischemia was induced for 10 minutes at 7th day, and immunohistochemistry was performed in the region of hippocampus of mongolian gerbils. According to the result of immunohistochemistry, the survival rates of neuroal cells in the hippocampal CA1 region are 37.8% in the high dose of musk containing WooHwangChungSimWon (HM-WHCSW) administrated group, 27.8% in low dose of civet containing WooHwangChungSimWon (LC-WHCSW), and 35.5% in high dose of civet containing WooHwangChungSimWon (HC-WHCSW) administrated group. These survial rates were significantly different from the survival rate of sham control group (14.4%). The results suggest that all the samples except the low dose of musk containing WooHwangChungSimWon (LM-WHCSW) have protective or preventive effects on cerebral ischemia.

• Journal of Korean Medicine Rehabilitation
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• v.20 no.3
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• pp.1-11
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• 2010

Objectives : This study was designed to investigate the effects of Lumbricus extract(LE) on the regional cerebral blood flow(rCBF) in ischemic rats, further to determine the mechanism of action of LE, and the effects that LE inhibits lactate dehydrogenase(LDH) activity in brain cells. Methods and materials : This study, ischemic rats were divided into total four group: control group(n=6), experimental group I (LE treated group)(n=6), experimental group II(LE treated group after pretreatment with indomethacin)(n=6), experimental group III(LE treated group after pretreatment with methylene blue)(n=6). And the measurement that LE inhibits LDH activity in the damage to brain cells to N-methyl-D-aspartic acid(NMDA). The changes of rCBF were determinated by laser-doppler flowmetry(LDF), and LDH activity was determinated by microplate reader in vitro. Results : 1. The rCBF was significantly improved by LE(10 mg/kg, i.p.) during the period of cerebral reperfusion, compared with the control group. 2. The rCBF was significantly increased by LE after pretreatment with indomethacin(1 mg/kg, i.p.), an inhibitor of cyclooxygenase, during the period of cerebral reperfusion, compared with the LE group, and rCBF was accelerated by LE after pretreatment with methylene blue($10{\mu}g/kg$, i.p.) an inhibitor of guanylate cyclase during the period of cerebral reperfusion, compared with the control group. 3. LE significantly inhibited LDH activity in vitro in a dose-dependent manner. Conclusions : From the above results, these were suggested that Lumbricus had anti-ischemia action in connection with cyclooxygenase and might prevent the brain cells death through inhibited LDH activity.

• Journal of Korean Academy of Nursing
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• v.36 no.7
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• pp.1232-1241
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• 2006

Purpose: The purpose of this study was to examine the effects of cerebral ischemia on Type I(soleus) and Type II(plantaris, gastrocnemius) muscles, and to determine the effects of isometric contraction training by electro- stimulation on Type I and II muscles in cerebral ischemia model rats. Method: Twenty-five male Sprague-Dawley rats were randomly divided into four groups: ST(stroke), STES(stroke+electrostimulation), SH(sham) and SHES (sham+electrostimulation). The ST and STES groups received a transient right middle cerebral artery occlusion operation. The SH and SHES groups received a sham operation. The STES and SHES groups had daily isometric contraction training by electrostimulation(100Hz, 45mA, 7.5V) on hindlimb muscles for 7days. Result: Plantaris and gastrocenmius muscle weight, myofibrillar protein contents of soleus and gastrocnemius, and the muscle fiber cross-sectional area of gastrocnemius in the ST group significantly decreased compared with the SH group. Soleus, plantaris, gastrocnemius muscle weight, myofibrillar protein contents of soleus and gastrocnemius, and the Type I muscle fiber cross-sectional area of soleus and the Type II muscle fiber cross-sectional area of gastrocnemius in the STES group significantly increased compared with the 57 group. Conclusion: Hindlimb muscle atrophy occurs after acute stroke and isometric contraction training by electrostimulation during early stages of a stroke attenuates muscle atrophy of Type I and Type II muscles.

• Journal of Acupuncture Research
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• v.34 no.3
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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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• v.50 no.3
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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.