• The Journal of Dong Guk Oriental Medicine
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• v.11
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• pp.58-65
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• 2008

Objectives : BHT has been commonly used to treatment of brain disorders in Oriental clinic in Korea. The purpose of this study was to determine the inhibitory effect of modified BHT-C extract on the transient forcal cerebral ischemia in rats. Method : We prepared ischemic rats by the transient middle cerebral artery occlution(MCAO; 90 min occlusion and 144 h reperfusion) in rat brains. BHT-C extract (100 and 200 mg/kg, i.p.) was administered every day after the onset of MCAO until 6 day. Result : BHT-C extract increased survival rate of ischemic rats compared with vehicle-treated rats. BHT-C extract treated rats (100 and 200 mg/kg) were shown a significant reduction in infarct volume compared with vehicle-treated rats. Conclusions : These results suggest that BHT-C extract may contribute to its protective effects in brain ischemia through the reduction of brain infarction.

• Journal of Korean Medical classics
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• v.20 no.2
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• pp.53-59
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• 2007

In Oriental medicine, different suggestions regarding how cerebrovascular accident(CVA) may develop have been offered by several physicians. In Jin(金)Yuan(元) dynasty, Liu Wan Su(劉完素) asserted that CVA was not developed by external PungSa(風邪) but internal HwaYul, which was noted in the "SoMunHyunKiWonByungSik". To verify experimentally Liu's HwaYul theory in rats, normothermic control group (37$^{circ}C$) and hypothermic test group (32$^{circ}C$) were subjected to transient middle cerebral artery occlusion(MCAO) of 1hour. In 7days after MCAO, the rats were sacrified and the volume of infarct and the size of edema were measured. The present findings expand our understanding of the pathophysiology as to the CVA which is related to the HwaYul theory.

• Physical Therapy Korea
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• v.15 no.4
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• pp.50-58
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• 2008

The purpose of this study was to investigate the effects of the task-oriented training according to the application time with the change of motor and cognition function. Focal ischemic brain injury was produced in Sprague-Dawley rats (20 rats, $250{\pm}50$ g) through middle cerebral artery occlusion (MCAo). Before MCAo induction, all rats were trained in treadmill training and Morris water maze training for 1 week. Then they were randomly divided into groups: Group I : MCAo induction ($n_1$=5), Grop II: the application for simple treadmill task training after. MCAo induction ($n_2$=5). Group III: the application for Morris water maze cognitive task training after MCAo induction ($n_3$=5). Group IV: the application for progressive treadmill task training and Morris water maze cognitive task training after MCAo induction ($n_4$=5). Modified limb placing tests (MLPTs) and motor tests (MTs) were performed to test motor function and then Morris water maze acquisition test (MWMAT) and Morris water maze retention test (MWMRT) were performed to test cognitive function. For MTs, there were significant interactions among the groups with the time (p<.001). Group IV showed the steeper increasing pattern than those in other Groups on the 7th and 14th day. For MLPTs, there were significant interactions among the groups with the time (p<.001). The scores in Group III. IV had showed the more decreasing pattern than those in Group I, II since the 7th day and 14th day. For MWMAT, there were significant interactions among the groups with the time (p<.001). Group II found the Quadrant circular platform showed the steeper decreasing pattern than that in Group I on the 9th, 10th, 11th and 12th day. Group III. IV found the quadrant circular platform showed the slower decreasing pattern than that in Group I, II, For MWMRT, there were significant differences among the four groups (p<.001). The time to dwell on quadrant circular platform in Group IV on the 13th day was the longest compared with other groups. These results suggested that the combined task training was very effective to improve the motor and cognition function for the rats affected on their focal ischemic brain injury.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.4
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• pp.818-824
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• 2009

This study aimed to evaluate the effect of purgation therapy with Natrii sulfas, a therapy for stroke patients with constipation in the oriental medicine, on the ischemic brain damage of the rats. The ischemic brain damage was induced by the middle cerebral artery occlusion (MCAO), Natrii sulafas was administered once after the MCAO. After 48 hours, expressions of Bax, Bcl-2, c-Fos, and HSP72 on the brain tissues were observed by immunohistochemistrical methods or technique. Purgation therapy with Natrii sulfas attenuated the excess of Bax expression caused by the ischemic brain damage. It was significant statistically in the penumbra of cerebral cortex, but not in the caudate putamen, of the MCAO rats. Purgation therapy with Natrii sulfas did not attenuate the excess of Bcl-2 expression caused by the ischemic brain damage. Purgation therapy with Natrii sulfas did not attenuate the excess of c-Fos expression caused by the ischemic brain damage. Purgation therapy with Natrii sulfas attenuated the excess of HSP72 expression caused by the ischemic brain damage. It was significant statistically in the penumbra of cerebral cortex, but not in the caudate putamen, of the MCAO rats. These results suggest that purgation therapy with Natrii sulfas has a neuroprotective effect on the ischemic brain damage and an anti-apoptotic effect.

• Journal of Oriental Neuropsychiatry
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• v.24 no.4
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• pp.419-434
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• 2013

Objectives: The object of this study is to observe the cognition and motor function recovery effects of Joojakwhan (JJW), a traditional Korean poly-herbal formula for treating various neuropsychiatric diseases such as dementia, for the mildly stroke rats, with 60 minutes of reperfusion transient middle cerebral artery occlusion (tMCAO). Methods: In the present study, 125, 250 and 500 mg/kg of JJW were orally administered, once per day for 10 continuous days 2 hours after the tMCAO. The body weight changes, infarct sizes under 2% 2, 3, 5-triphenyl tetrazolium chloride (TTC) stain, sensorimotor functions and cognitive motor behavior tests were serially monitored with cerebral caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP)-immunoreactivities and histopathological changes. The effects of tMCAO on sensorimotor functions were evaluated by using of limb placing and body-swing tests, and the cognitive motor behaviors were also observed with water maze tests. Results: From the results of tMCAO, with marked decreases of body weights, disorders of sensorimotor functions increases the limb placing test scores, and decrease the numbers and percentages of body swings to the ipsilateral sides. The cognitive motor behaviors increases the distances and time to reach the escape platform which included the inhibitions of the decreases with repeated trials that were observed with focal cerebral cortex infarct volumes. In addition, the marked increases of the atrophy, numbers of degeneration, caspase-3- and PARP-immunoreactive cells around peri-infarct ipsilateral cerebral cortex were also observed in tMCAO controls when compared with the sham control rats, respectively. Conclusions: The results obtained from this study suggest that oral administrations of JJW indicate obvious cognitions and motor function recoveries of the rats with tMCAO, mild strokes, which are mediated by neuro-protective effects through known antioxidant effects of components.

• Journal of Pharmacopuncture
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• v.14 no.3
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• pp.5-17
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• 2011

Objectives : Gliosis becomes physical and mechanical barrier to axonal regeneration. Reactive gliosis induced by middle cerebral artery occlusion is involved with up-regulation of CD81 and GFAP (Glial fibrillary acidic protein). The current study is to examine the effect of the Angelica gigas Nakai(intravenous injection. 100 mg/kg twice in a day) on CD81 and GFAP of the rat in the brain after middle cerebral artery occlusion. Methods : Cerebral infarction was induced by middle cerebral artery occlusion. And after intravenous injection of water extract of Angelica gigas Nakai, the size of cerebral infarction was measured. Examination of optical microscope were also used to detect the expression of CD81 and GFAP in the brain of the rat. Results : The following results were obtained : We found that size of cerebral infarcion induced by MCAO (Middle Cerebral Artery Occlusion) in rats were decreased after intravenous injection of Angelica gigas Nakai. We injected the extract of Angelica gigas Nakai to the MCAO in rats, and the optical microscope study showed that Angelica gigas Nakai had effect on protecting the cells of hippocampus. We found that GFAP, CD81 and ERK of the brain in rats with cerebral infarction after MCAO were meaningfully decreased after intravenous injecting Angelica gigas Nakai. We found that c-Fos expression of the brain in rats with cerebral infarction after MCAO were significantly increased after intravenous injecting Angelica gigas Nakai. Conclusions : These results indicate that Angelica gigas Nakai could suppress the reactive gliosis, which disturbs the astrocyte regeneration in the brain of the rat with cerebral infarction after MCAO by controlling the expression of CD81 and GFAP. And the effect may be modulated by the up-regulation of c-Fos and ERK.

• Physical Therapy Korea
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• v.14 no.3
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• pp.48-56
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• 2007

Environmental Enrichment (EE) alone is not capable of enhancing the fine digit and the forelimb functions. Therefore, we applied modified constraint-induced movement therapy (mCIMT) under the influence of EE to assess its effect on promoting improved forelimb sensorimotor functions. Focal ischemic brain injury was produced in Sprague-Dawley rats (60 rats, $250{\pm}50$ g) through middle cerebral artery occlusion (MCAO). Before MCAO induction, all rats were trained in modified limb placing tests and reaching tasks for 1 week. Then they were randomly divided into three groups: Group I: application of standard environment (SE) after MCAO induction (n=20), Group II: application of EE after MCAO induction (n=20), Group III: MCAO+EE, mCIMT and task-oriented training that was initiated at 10th day after MCAO induction (n=20). We also applied mCIMT (between 9 AM and 5 PM/daily) which included restraining the forelimb ipsilateral to the lesion using the 'Jones & Schallert' method. We assessed the change of modified limb placing, single pellet reaching test and the immunoreactivity of BDNF by immunohistochemistry (pre, 1st, 5th, 10th and 20th day). Group I showed no improved outcome, whereas group II and III significantly improved on the use of the forelimb and the immunoreactivity. The qualitative analysis of the skilled reaching test, of group III showed the greatest improvement in the fine digit and the forelimb function. These results suggest that EE combined with mCIMT is more functional in promoting enhanced fine digit and forelimb functional movements.

• Transactions on Electrical and Electronic Materials
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• v.16 no.2
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• pp.65-69
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• 2015

Low level laser therapy (LLLT) has facilitated an improvement in acupuncture treatment. In this study, we stimulated Shaochong (HT9), Dadun (LR1), Shaohai (HT3), and Yingu (KI10) acupoints with pulsed laser diodes 532 nm [green laser] and 658 nm [red laser] in rats with induced middle cerebral artery occlusion(MCAO). The animals were divided into 6 groups: intact control; MCAO control without LLLT; LLLT with red laser at HT9·LR1 and HT3·KI10 (RR); LLLT with green laser at HT9·LR1 and HT3·KI10 (GG); LLLT with green laser at HT9·LR1 and red laser at HT3·KI10 (GR); and LLLT with red laser at HT9·LR1 and green laser at HT3·KI10 (RG). We evaluated the immunohistochemical changes in the hippocampal CA1 region, and complete blood count changes. Compared to the MCAO control group, the RG group showed a significant decrease in Bax and cytochrome c levels in the hippocampus, and a significant increase in hemoglobin level, hematocrit, total white blood cell, neutrophil, lymphocyte, monocyte, and erythrocyte counts.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.2
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• pp.77-81
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• 2004

The loss of neurons and synaptic contacts following cerebral ischemia may lead to a synaptic plastic modification, which may contribute to the functional recovery after a brain lesion. Using synapsin I and GAP-43 as markers, we investigated the neuronal cell death and the synaptic plastic modification in the rat hippocampus of a middle cerebral artery occlusion (MCAO) model. Cresyl violet staining revealed that neuronal cell damage occurred after 2 h of MCAO, which progressed during reperfusion for 2 weeks. The immunoreactivity of synapsin I and GAP-43 was increased in the stratum lucidum in the CA3 subfield as well as in the inner and outer molecular layers of dentate gyrus in the hippocampus at reperfusion for 2 weeks. The immunoreactivity of phosphosynapsin was increased in the stratum lucidum in the CA3 subfield during reperfusion for 1 week. Our data suggest that the increase in the synapsin I and GAP-43 immunoreactivity probably mediates either the functional adaptation of the neurons through reactive synaptogenesis from the pre-existing presynaptic nerve terminals or the structural remodeling of their axonal connections in the areas with ischemic loss of target cells. Furthermore, phosphosynapsin may play some role in the synaptic plastic adaptations before or during reactive synaptogenesis after the MCAO.

• Biomolecules & Therapeutics
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• v.28 no.2
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• pp.152-162
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• 2020

Cerebral ischemia exhibits a multiplicity of pathophysiological mechanisms. During ischemic stroke, the reactive oxygen species (ROS) concentration rises to a peak during reperfusion, possibly underlying neuronal death. Recombinant human erythropoietin (EPO) supplementation is one method of treating neurodegenerative disease by reducing the generation of ROS. We investigated the therapeutic effect of PEGylated EPO (P-EPO) on ischemic stroke. Mice were administered P-EPO (5,000 U/kg) via intravenous injection, and middle cerebral artery occlusion (MCAO) followed by reperfusion was performed to induce in vivo ischemic stroke. P-EPO ameliorated MCAO-induced neurological deficit and reduced behavioral disorder and the infarct area. Moreover, lipid peroxidation, expression of inflammatory proteins (cyclooxygenase-2 and inducible nitric oxide synthase), and cytokine levels in blood were reduced by the P-EPO treatment. In addition, higher activation of nuclear factor kappa B (NF-κB) was found in the brain after MCAO, but NF-κB activation was reduced in the P-EPO-injected group. Treatment with the NF-κB inhibitor PS-1145 (5 mg/kg) abolished the P-EPO-induced reduction of infarct volume, neuronal death, neuroinflammation, and oxidative stress. Moreover, P-EPO was more effective than EPO (5,000 U/kg) and similar to a tissue plasminogen activator (10 mg/kg). An in vitro study revealed that P-EPO (25, 50, and 100 U/mL) treatment protected against rotenone (100 nM)-induced neuronal loss, neuroinflammation, oxidative stress, and NF-κB activity. These results indicate that the administration of P-EPO exerted neuroprotective effects on cerebral ischemia damage through anti-oxidant and anti-inflammatory properties by inhibiting NF-κB activation.