• 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 Oriental Neuropsychiatry
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• v.26 no.3
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• pp.319-336
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• 2015

Objectives: The object of this study was to evaluate the cognition and motor function recovery effects of Sungshim-san (SSS), a traditional Korean cardio-protective polyherbal formula in the severe rat stroke, permanent middle cerebral artery occlusion (pMCAO) model. Methods: The experimental animals were divided into 6 groups. SSS aqueous extracts (yield=16.82%; 400, 200 and 100 mg/kg) were administered orally by using Sonde, once daily, for 28 continuous days from 24 hrs post-pMCAO. Donepezil 10 mg/kg, a representative drug for dementia, was used as a reference drug. The body weight changes, infarct/defect sizes, sensorimotor function and cognitive motor behavior were serially monitored. Limb placing and body-swing test for sensorimotor functions were conducted at 1 day before operation (base line), and 1, 3, 7, 14, 21 and 28 days post-pMCAO; and water maze test for the cognitive motor behavior was conducted at 14 and 28 days post-pMCAO, respectively. Results: Focal cerebral cortex infarct and defects due to pMCAO resulted in marked decreases of body weight, disorders of sensorimotor functions and cognitive motor behaviors. However, the pMCAO-related ischemic damages were markedly and dose-dependently inhibited by treatment with SSS 400 and 200 mg/kg, respectively. Donepezil markedly decreased the body weight and gains, as compared with pMCAO control rats; however, SSS 400 and 200 mg/kg favorably ameliorated the pMCAO-induced decreases in body weight and gains. SSS 100 mg/kg treated rats did not show any favorable effects on the pMCAO-related ischemic damages, as compared with pMCAO control rats. Conclusions: The results of the study indicated that oral administration of SSS 400 and 200 mg/kg accelerated cognition and motor function recovery in the rat pMCAO model. The treatment effect was potentially mediated by neuroprotection via the known augmentation of cerebral antioxidant defense system of SSS itself or its individual herbal components. Especially, the overall effects of SSS 200 mg/kg were similar to those of donepezil 10 mg/kg, but less toxic.

• Physical Therapy Korea
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• v.16 no.4
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• pp.44-52
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• 2009

It is known that individual factors as cognitive, perception, emotion, and motivation may greatly influence on recovery from neurologic region. This study was to investigate the effects of environmental reinforcement through motivation to perform the tasks voluntarily on motor and cognition function in rats with focal ischemic brain injury. Focal ischemic brain injury was induced in Sprague-Dawley rats (15 rats, $250{\pm}50$ g) through middle cerebral artery occlusion (MCAo). And then, experiment groups were randomly divided into three groups; The control group: MCAo induction ($n_1$=5), the environmental reinforcement (ER) group: the application for ER after MCAo induction ($n_2$=5), the environmental reinforcement through motivation (ERM) group: the application for ERM after MCAo induction ($n_3$=5). The climbing test (CT) and the modified limb placing tests (MLPTs) to measure the motor function and the Morris water maze acquisition test (MWMAT) and the Morris water maze retention test (MWMRT) to measure the cognitive function were performed. For the CT, the ERM group was significantly larger than the ER group. For the MLPTs, the ERM group was significantly decreased compared to other groups. For the MWMAT, the time to find the circular platform in the ERM group significantly decreased compared to other groups. For the MWMRT, the time to dwell on the quadrant circular platform in the ERM group was significantly increased compared to other groups. These results suggested that the ERM could improve the motor and cognitive functions in the rats with focal ischemic brain injury.

• Physical Therapy Korea
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• v.12 no.3
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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.

• 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.

• 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.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.

• Molecules and Cells
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• v.40 no.2
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• pp.133-142
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• 2017

Previous studies have shown that bone marrow mesenchymal stromal cell (MSC) transplantation significantly improves the recovery of neurological function in a rat model of intracerebral hemorrhage. Potential repair mechanisms involve anti-inflammation, anti-apoptosis and angiogenesis. However, few studies have focused on the effects of MSCs on inducible nitric oxide synthase (iNOS) expression and subsequent peroxynitrite formation after hypertensive intracerebral hemorrhage (HICH). In this study, MSCs were transplanted intracerebrally into rats 6 hours after HICH. The modified neurological severity score and the modified limb placing test were used to measure behavioral outcomes. Blood-brain barrier disruption and neuronal loss were measured by zonula occludens-1 (ZO-1) and neuronal nucleus (NeuN) expression, respectively. Concomitant edema formation was evaluated by H&E staining and brain water content. The effect of MSCs treatment on neuroinflammation was analyzed by immunohistochemical analysis or polymerase chain reaction of CD68, Iba1, iNOS expression and subsequent peroxynitrite formation, and by an enzyme-linked immunosorbent assay of pro-inflammatory factors (IL-$1{\beta}$ and TNF-${\alpha}$). The MSCs-treated HICH group showed better performance on behavioral scores and lower brain water content compared to controls. Moreover, the MSC injection increased NeuN and ZO-1 expression measured by immunochemistry/immunofluorescence. Furthermore, MSCs reduced not only levels of CD68, Iba1 and pro-inflammatory factors, but it also inhibited iNOS expression and peroxynitrite formation in perihematomal regions. The results suggest that intracerebral administration of MSCs accelerates neurological function recovery in HICH rats. This may result from the ability of MSCs to suppress inflammation, at least in part, by inhibiting iNOS expression and subsequent peroxynitrite formation.