• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.2
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• pp.586-595
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• 2004

Kamidojuk-San (KDJS) is known to be effective for treating cardiovascular diseases such hypertension, and clinically applied for the treatment of cerebral palsy or stoke patients. Yet, the overall mechanisms underlying its activity at the cellular levels are not known. Using experimental animal system, we investigated whether KDJS has protective effects on cells in cardiovascular and nervous systems. KDJS was found to rescue death of cultured primary neurons induced by AMPA, NMDA and kainate as well as BSO and Fe/sup 2+/ treatments. Moreover, KDJS treatment promoted animal's recovery from coma induced by a lethal dose of KCN treatment, and improved survival in animals exposed to lethal dose of KCN. Neurological examinations further showed that KDJS reduced the time which is required for animals to respond in terms of forelimb and hindlimb movements. To examine its physiological effects on cardiovascular and nervous systems, we induced ischemic injury in hippocampal neurons and cerebral neurons by middle cerebral artery (MCA) occlusion. Histological examination revealed that KDJS significantly protected neurons from ischemic damage. Thus, the present data suggest that KDJS may play an important role in protecting cells of cardiovascular and nervous systems from external noxious stimulations.

• Archives of Pharmacal Research
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• v.23 no.4
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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 Korea Journal of Herbology
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• v.25 no.2
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• pp.71-79
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• 2010

Objectives : In this study, the neuroprotective effects of modified Boyanghwano-Tang (mBHT) and the major medicinal plants, Astragali Radix(AR) and Salviae Miltiorrhizae Radix(SMR) were investigated in transient middle cerebral artery occlusion (tMCAO)-induced ischemic stroke of rats. Methods : mBHT(400 mg/kg) and AR(154 mg/kg) or SMR(62 mg/kg) water extract orally injected in rats after 90 min occlusion of MCA and then allow reperfusion to 24 h. Brain infarction was measured by TTC staining and the expressions of NOS isoforms and apoptotic molecules were determined in ischemic brain by Western blot. Results : The results showed that mBHT has stronger neuropreotective property through inhibitions of the PARP cleaved and caspase-3 activation in ischemic rats, and could reduced infarction volumes comparison of those of AR or SMR, respectively. While, AR extract has an angiogenic property through increasing the expressions of eNOS and VEGF, and SMR extract has a strong anti-inflammatory effects through inhibition of iNOS expression in ischemic brains. Conclusions : These results suggest that mBHT has multifactorial therapeutic advantages through anti-apoptosis, anti-inflammation and angiogenesis for ischemic stroke based on a synergistic combination of ingradients rather than monotherapy.

• The Journal of Korean Medicine
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• v.30 no.2
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• pp.1-16
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• 2009

Objectives: This study investigated the effect of Yukmijihwangtang on cerebral ischemia-induced learning and memory impairment by middle cerebral artery (MCA) occlusion in rats. Methods: The ability of learning and memory of rats was measured using the eight-arm radial maze and the passive avoidance test, and profile of cholinergic neuron was assessed in the medial septum and hippocampus region by immuno-histochemistry. Results: 1. No differences were found between groups in the number of correct choices in acquisition performance during the eight-arm radial maze task. 2. No differences were found between groups on day 1 in the error rate in acquisition performance, which is defined as the number of enters into the same arm more than once within five minutes. After 5 to 6 days of test, the number of errors was significantly reduced in the Yukmijihwangtang group (forebrain ischemia group with Yukmijihwangtang treatment), compared with the ischemia group. 3. The memory processes significantly improved in the Yukmijihwangtang group according to results of the passive avoidance test. 4. The appearance of AchE (acetylcholinesterase) in the CA1 region of hippocampus significantly decreased in the ischemia group, compared with the sham group (untreated group). The appearance of AchE in the same region significantly increased in the Yukmijihwangtang group, compared with the ischemia group. 5. The appearance of ChAT (choline acetyltransferase) in the CA1 region of the hippocampus and medial septum decreased in the ischemia group, compared with the sham group. The appearance of ChAT in the same region significantly increased in the Yukmijihwangtang group, compared with the ischemia group Conclusions: This study provides evidence that Yukmijihwangtang is effective for reviving the ability of learning and memory and damaged neurons in rats with experimental cerebral ischemia.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.4
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• pp.1014-1020
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• 2006

This study was intended to examine the effects of electroacupuncture(EA) and therapeutic exercise on the improvement of exercise function, BNDF, and HSP70 protein expression in an ischemic stroke model induced by MCA occlusion. Experiments were conducted for 1, 3 days, 1, 8 weeks respectively. Group I was a group of EA and therapeutic exercise; Group II was a group of therapeutic exercise; Group III was a group of EA; Group IV was a sham group of EA; Group V was a control group; and Group VI was a sham group without ischemic stroke. In each group, neurologic motor behavior test, histologic observations, BDNF, and HSP70 expression were observed and analyzed. The following results were obtained. The results of behavior test suggest that 8 weeks after ischemic stroke was induced, Group I improved in degeneration and inflammation of muscle fiber and decreased in destruction of nerve cells and cerebral infarction, indicating a similar state of muscle fiber and brain to Group VI. In immunohistochemical observations, Group I showed increase in BDNF and decrease in HSP70. Based on these results, EA and therapeutic exercise may improve muscle atrophy and change in BDNF and HSP70 expression of ischemic stroke rats and contribute to the improvement of exercise function.

• The Korean Journal of Pain
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• v.21 no.2
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• pp.119-125
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• 2008

Background: Cerebral blood vessels are innervated by sympathetic nerves from the superior cervical ganglia (SCG), and these nerves may influence the cerebral blood flow. The purpose of the present study was to evaluate the neuroprotective effect of superior cervical sympathetic ganglion block in rats that were subjected to focal cerebral ischemia/reperfusion injury. Methods: Eighty male Sprague-Dawley rats (270-320 g) were randomly assigned to one of two groups (the ropivacaine group and a control group). In all the animals, brain injury was induced by middle cerebral artery (MCA) reperfusion that followed MCA occlusion for 2 hours. The animals of the ropivacaine group received $30{\mu}l$ of 0.75% ropivacaine, and their SCG. Neurologic score was assessed at 1, 3, 7 and 14 days after brain injury. Brain tissue samples were then collected. The infarct ratio was measured by 2.3.5-triphenyltetrazolium chloride staining. The terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeled (TUNEL) reactive cells and the cells showing caspase-3 activity were counted as markers of apoptosis at the caudoputamen and frontoparietal cortex. Results: The death rate, the neurologic score and the infarction ratio were significantly less in the ropivacaine group 24 hr after ischemia/reperfusion injury. The number of TUNEL positive cells in the ropivacaine group was significantly lower than those values of the control group in the frontoparietal cortex at 3 days after injury, but the caspase-3 activity was higher in the ropivacaine group than that in the control group at 1 day after injury. Conclusions: The study data indicated that a superior cervical sympathetic ganglion block may reduce the neuronal injury caused by focal cerebral ischemia/reperfusion, but it may not prevent the delayed damage.

• The Korean Journal of Nuclear Medicine
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• v.30 no.4
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• pp.484-492
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• 1996

To detect ischemic tissue in experimental model of cerebral ischemia made by middle cerebral artery(MCA)-occlusion, we acquired triple image of $^{99m}Tc$-glucarate, [$^{18}F$]fluoro-deoxyglucose (FDG), and 2,3,5- triphenyltetrazolium (TTC) staining. We made cerebral infarction either with reperfusion (after occlusion of 2 hours) or without reperfusion in 10 Sprague-Dawley rats by inserting thread to MCA through internal carotid artery. After 22 hours, we injected 740 MBq of $^{99m}Tc$-glucarate and 55.5 MBq of [$^{18}F$]FDG through tail vein. Each 1 mm slice of rat brains was frozen and exposed to imaging plate for 20 minutes in freezer to get an [$^{18}F$]FDG image. After 20 hours enough to fade radioactivity of [$^{18}F$]FDG, the slices were again imaged by BAS1500 for $^{99m}Tc$-glucarate uptake. Finally, these brain tissues were stained with TTC. Semi-quantitative visual analysis was done by grading 0 to 3 points according to the degree of uptakes($^{99m}Tc$-glucarate) and decreased uptakes([$^{18}F$]FDG and TTC). Ten rats survived with neurologic symptoms. TTC staining confirmed the development of infarction. The size of the infarction was relatively larger in the group without reperfusion. [$^{18}F$]FDG images were similar to TTC-stained images. However, we found regions with intermediate uptake which were not stained with TTC. We found regions with intermediate [$^{18}F$]FDG uptake where TTC staining was normal. $^{99m}Tc$-glucarate uptake was round only in TTC non-stained region. In the TTC stained regions, there were no uptake of $^{99m}Tc$-glucarate. We could not find clear relation between $^{99m}Tc$-glucarate uptake with [$^{18}F$]FDG uptake. This was partly because percent uptake of $^{99m}Tc$-glucarate was so small (less than 1 percent of injected dose) and because there were quite heterogeneity of patterns of [$^{18}F$]FDG uptake and TTC. With these findings, we could conclude that $^{99m}Tc$-glucarate were taken up only in part of ischemic tissues which were proven to be nonviable. The establishment of MCA-occluded rat model with or without reperfusion and triple imaging for $^{99m}Tc,\;^{18}F$ and TTC helped the characterization of $^{99m}Tc$-glucarate uptakes. Further work is needed to clarify the meaning or diversities or [$^{18}F$]FDG and TTC and their relation with $^{99m}Tc$-glucarate.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.5
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• pp.275-280
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• 2008

A brief ischemic insult induces significant protection against subsequent massive ischemic events. The molecular mechanisms known as preconditioning (PC)-induced ischemic tolerance are not completely understood. We investigated whether kinetic changes of cyclooxygenase (COX)-2 during reperfusion time-periods after PC were related to ischemic tolerance. Rats were given PC by occlusion of middle cerebral artery (MCAO) for 10 min and sacrificed after the indicated time-periods of reperfusion (1, 2, 4, 8, 12, 18 or 24 h). In PC-treated rats, focal ischemia was induced by occlusion of MCA for 24 h and brain infarct volume was then studied to determine whether different reperfusion time influenced the damage. We report that the most significant protection against focal ischemia was obtained in rats with 8 h reperfusion after PC. Administration of indomethacin (10 mg/kg, oral) or rofecoxib (5 mg/kg, oral) 48 h prior to PC counteracted the effect of PC. Immunohistochemical analysis showed that COX-2 and HO-l protein were induced in PC-treated rat brain, which was significantly inhibited by rofecoxib. Taken together, we concluded that the kinetic changes of COX-2 expression during the reperfusion period after PC might be partly responsible for ischemic tolerance.

• The Korean Journal of Pain
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• v.20 no.2
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• pp.83-91
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• 2007

Background: Cerebral blood vessels are innervated by sympathetic nerves that originate in the superior cervical ganglia (SCG). This study was conducted to determine the effect of an SCG block on brain injury caused by focal cerebral ischemia/reperfusion in a rat model. Methods: Male Sprague-Dawley rats (270-320 g) were randomly assigned to one of three groups (lidocaine, ropivacaine, and control). After brain injury induced by middle cerebral artery (MCA) occlusion/reperfusion, the animals were administered an SCG bloc that consisted of $30{\mu}l$ of 2% lidocaine or 0.75% ropivacaine, with the exception of animals in the control group, which received no treatment. Twenty four hours after brain injury was induced, neurologic scores were assessed and brain samples were collected. The infarct and edema ratios were measured, and DNA fragmented cells were counted in the frontoparietal cortex and the caudoputamen. Results: No significant differences in neurologic scores or edema ratios were observed among the three groups. However, the infarct ratio was significantly lower in the ropivacaine group than in the control group (P < 0.05), and the number of necrotic cells in the caudoputamen of the ropivacaine group was significantly lower than in the control group (P < 0.01). Additionally, the number of necrotic and apoptotic cells in theropivacaine group were significantly lower than inthe control group in both the caudoputamen and the frontoparietal cortex (P < 0.05). Conclusions: Brain injury induced by focal cerebral ischemia/reperfusion was reduced by an SCG block using local anesthetics. This finding suggests that a cervical sympathetic block could be considered as another treatment option for the treatment of cerebral vascular diseases.

• Journal of Korean Biological Nursing Science
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• v.4 no.1
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• pp.51-69
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• 2002

The purpose of this study was to identify the effect of cerebral ischemia on affected(Lt) and unaffected(Rt) side of soleus, plantaris and gastrocnemius muscle mass and determine the effect of exercise on affected and unaffected side on soleus, plantaris and gastrocnemius muscle mass during acute stage of stroke. Sixteen male Sprague-Dawley rate with 200-270g body weight were randomly divided into three groups: control, stroke, and exercise after stroke(St+Ex) group. The control group received sham operation and the stroke group and St+Ex group received transient right MCA(middle cerebral artery) occlusion operation. The St+Ex groups ran on a treadmill for 20min/day at 10m/min and $10^{\circ}$ grade for 6days. During the experimental period body weight and diet intake was measured every morning. On the 7th day after operation, muscles were dissected from both affected and unaffected side of hindlimb. Cerebral infarction of stroke and St+Ex groups were identified by staining with TCC for 30 minutes. The data were analyzed by Kruskal-Wallis test and Mann-Whitney U test using the SPSSWIN 9.0 program. Significance was accepted at the level of p<0.05. The results were summarized follows : 1) There were no significant difference of the body weight on the first day of experiment among 3 groups. Whereas on the 7th day, the body weight of both stroke group and St+Ex group were significantly smaller than that of control group. Body weight of St+Ex group on the 7th day tended to be larger than that of stroke group. 2) Total diet intake of both stroke group and St+Ex group were also significantly smaller than that of control group. While total amount of diet intake in St+Ex group tended to be larger than that of stroke group. 3) The weight of gastrocnemius muscle of affected side in stroke group significantly decreased compared to that of control group and the weight of soleus and plantaris muscle of affected side in stroke group tended to decrease compared to that of control group. 4) The weight of plantaris muscle of unaffected side in stroke group significantly decreased compared to that of control group and the weight of soleus and gastrocnemius muscle of unaffected side in stroke group tended to decrease compared to those of control group. 5) The weight of gastrocnemius muscle of affected side in stroke group significantly decreased compared to that of unaffected side and there was no significant difference of the weight of soleus and plantaris muscle in stroke group between affected side and unaffected side. 6) The weight of soleus, plantaris and gastrocnemius muscle of both affected side and unaffected side in St+Ex group had a tendency of increase compared to those of stroke group. The relative weight of soleus and gastrocnemius muscle of affected side and soleus muscle of unaffected side in St+Ex group had a tendency to increase compared to those of stroke group. Based on these results, exercise during acute stage of stroke might attenuate muscle atrophy of both affected and unaffected side of hindlimb muscles.