• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.1
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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.

• Biomolecules & Therapeutics
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• v.28 no.6
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• pp.512-518
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• 2020

Stroke is a leading cause of long-term disability in ischemic survivors who are suffering from motor, cognitive, and memory impairment. Previously, we have reported suppressing LPA₅ activity with its specific antagonist can attenuate acute brain injuries after ischemic stroke. However, it is unclear whether suppressing LPA₅ activity can also attenuate chronic brain injuries after ischemic stroke. Here, we explored whether effects of LPA₅ antagonist, TCLPA5, could persist a longer time after brain ischemic stroke using a mouse model challenged with tMCAO. TCLPA5 was administered to mice every day for 3 days, starting from the time immediately after reperfusion. TCLPA5 administration improved neurological function up to 21 days after tMCAO challenge. It also reduced brain tissue loss and cell apoptosis in mice at 21 days after tMCAO challenge. Such long-term neuroprotection of TCLPA5 was associated with enhanced neurogenesis and angiogenesis in post-ischemic brain, along with upregulated expression levels of vascular endothelial growth factor. Collectively, results of the current study indicates that suppressing LPA₅ activity can provide long-term neuroprotection to mice with brain ischemic stroke.

• The Journal of Korean Physical Therapy
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• v.19 no.4
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• pp.33-41
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• 2007

Purpose: To investigate environmental enrichment and nerve stimulation follows in application times with the change of BDNF & Trk-B receptor in the motor cortex and spinal cord. Methods: Experimental groups were divided into the five groups. Group I: normal control group, Group II: experiment control group, Group III: sciatic never electrical stimulation after MCAO, Group IV: application of only environmental enrichment after MCAO, Group V: never electrical stimulation with environmental enrichment after MCAO. Histologic observation and coronal sections were processed individually in goat polyclonal antibody phosphorylated BDNF and rabbit polyclonal antibody Trk-B receptor. Results: In immunohistochemistric response of BDNF and Trk-B, group II were showed that lower response effect at postischemic 1 days, 3 days, and 7 days. Group V were showed that increase response effect at postischemic 3 days, 7 days and 14 days. Specially showed that the most response effect at postischemic 14 days. In neurobehavioral assessment, group V were significantly difference from other groups on between-subject effects. Conclusion: The above results suggest that combined environmental enrichment with peripheral nerve electrical stimulation in focal ischemic brain injury were more improved that the change of BDNF & Trk-B receptor expression than non treatment.

• The Journal of the Korea Contents Association
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• v.11 no.4
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• pp.273-282
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• 2011

This study was to investigate the effect of improve forelimb sensorimotor function and neurotrophic factor(GAP-43) expression when differing an application time of tDCS in ischemic brain injury rat model(pre, $1^{st}$, $7^{th}$, $14^{th}$). Focal ischemic brain injury was induced in 80 Sprague-Dawley rats through middle cerebral artery occlusion(MCAO) by 'Longa' method. And then experimental groups were randomly divided into four groups; GroupI: MCAO induction, GroupII: application of tDCS(10 min) after MCAO induction, GroupIII: application of tDCS(20 min) after MCAO induction, GroupIV: application of tDCS(30 min) after MCAO induction. Modified limb placing test and single pellet reaching test were performed to test forelimb sensorimotor function. And the histological examination was also observed through the immunohistochemistric response of GAP-43(growth-associated protein-43) in the cerebral cortex. In modified limb placing test, groupIII(p<0.05) showed significantly improve than the other groups on $14^{th}$). day. In single pellet reaching test, groupIII(p<0.01) and groupIV(p<0.05) significantly improved on $14^{th}$) day. And in immunohistochemistric response of GAP-43, group III showed significantly positive response than the other groups on $14^{th}$ day. These results suggest that the intensity(0.1 mA)/time(20 min) condition of tDCS application has a significant impact on the sensorimotor functional recovery in focal ischemic brain injury rat models.

• Journal of Ginseng Research
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• v.46 no.2
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• pp.275-282
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• 2022

Background: Stroke is a neurological disorder characterized by brain tissue damage following a decrease in oxygen supply to brain due to blocked blood vessels. Reportedly, 80% of all stroke cases are classified as cerebral infarction, and the incidence rate of this condition increases with age. Herein, we compared the efficacies of Korean White ginseng (WG) and Korean Red Ginseng (RG) extracts (WGex and RGex, respectively) in an ischemic stroke mouse model and confirmed the underlying mechanisms of action. Methods: Mice were orally administered WGex or RGex 1 h before middle cerebral artery occlusion (MCAO), for 2 h; the size of the infarct area was measured 24 h after MCAO induction. Then, the neurological deficit score was evaluated and the efficacies of the two extracts were compared. Finally, their mechanisms of action were confirmed with tissue staining and protein quantification. Results: In the MCAO-induced ischemic stroke mouse model, WGex and RGex showed neuroprotective effects in the cortical region, with RGex demonstrating superior efficacy than WGex. Ginsenoside Rg1, a representative indicator substance, was not involved in mediating the effects of WGex and RGex. Conclusion: WGex and RGex could alleviate the brain injury caused by ischemia/reperfusion, with RGex showing a more potent effect. At 1,000 mg/kg body weight, only RGex reduced cerebral infarction and edema, and both anti-inflammatory and anti-apoptotic pathways were involved in mediating these effects.

• 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 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.

• 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.