• 대한물리의학회지
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• 제7권1호
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• pp.11-20
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• 2012

Purpose : This study is intended to examine the repetitive transcranial magnetic stimulation on cognitive function in the focal ischemic stroke rat model. Methods : This study selected 30 Sprague-Dawley rats of 8 weeks. The groups were divided into two groups and assigned 15 rats to each group. Control group: Non-treatment after injured by focal ischemic stroke; Experimental group: application of repetitive transcranial magnetic stimulation(0.1 Tesla, 25 Hz, 20 min/time, 2 times/day, 5 days/2 week) after injured by focal ischemic stroke. To assess the effect of rTMS, the passive avoidance test, spatial learning and memory ability test were analyzed at the pre, 1 day, $7^{th}$ day, $14^{th}$ day and immunohistochemistric response of BDNF were analyzed in the hippocampal dentate gyrus at $7^{th}$ day, $14^{th}$ day. Results : In passive avoidance test, the outcome of experimental group was different significantly than the control group at the $7^{th}$ day, $14^{th}$ day. In spatial learning and memory ability test, the outcome of experimental group was different significantly than the control group at the $7^{th}$ day, $14^{th}$ day. In immunohistochemistric response of BDNF in the hippocampal dentate gyrus, experimental groups was more increased than control group. Conclusion : These result suggest that improved cognitive function by repetitive transcranial magnetic stimulation after focal ischemic stroke is associated with dynamically altered expression of BDNF in hippocampal dentate gyrus and that is related with synaptic plasticity.

• 동의생리병리학회지
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• 제18권2호
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• pp.538-543
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• 2004

Objective : This study investigated a neuroprotective effect of Puerariae Radix on cerebral ischemia. Method : The global cerebral ischemia was induced by bilateral common carotid arteries occlusion under hypotension (40mmHg) in Sprague-Dawley rats. After the treatment of Puerariae Radix extract, changes of c-Fos and c-Jun expressions, immediate early genes expressed by cerebral ischemia, in the hippocampus were observed immunohistochemically. Result: The results obtained are as follows; The significant increases of c-Fos and c-Jun expressions were observed in the hippocampus of the ischemic damaged rat brains. Then Puerariae Radix treatment demonstrated significant decreases of c-Fos and c-Jun expressions in CA1 region and dentate gyrus as compared with control group. On the upregulated c-Fos expression induced by cerebral ischemia, Puerariae Radix treatment demonstrated significant decreases of c-Fos expressions in CA1 region (P<0.01) and dentate gyrus (P<0.05) as compared to the control group, but there were not a significant changes in CA2 and CA3 regions of the hippocampus. On the upregulated c-Jun expression induced by cerebral ischemia, Puerariae Radix treatment demonstrated significant decrease of c-Jun expression in CA1 region (P<0.05) as compared to the control group, but there were not a significant changes in CA2, CA3, and dentate gyrus of the hippocampus. Conclusion : These results suggested that Puerariae Radix reveals the neuroprotective effect through the reduction of immediate early genes, c-Fos and c-Jun, induced by cerebral ischemia.

• The Korean Journal of Physiology and Pharmacology
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• 제22권2호
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• pp.145-153
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• 2018

The subgranular zone (SGZ) of hippocampal dentate gyrus (HDG) is a primary site of adult neurogenesis. Toll-like receptors (TLRs), are involved in neural system development of Drosophila and innate immune response of mammals. TLR2 is expressed abundantly in neurogenic niches such as adult mammalian hippocampus. It regulates adult hippocampal neurogenesis. However, the role of TLR2 in adult neurogenesis is not well studied in global or focal cerebral ischemia. Therefore, this study aimed to investigate the role of TLR2 in adult neurogenesis after photochemically induced cerebral ischemia. At 7 days after photothrombotic ischemic injury, the number of bromodeoxyuridine (BrdU)-positive cells was increased in both TLR2 knock-out (KO) mice and wild-type (WT) mice. However, the increment rate of BrdU-positive cells was lower in TLR2 KO mice compared to that in WT mice. The number of doublecortin (DCX) and neuronal nuclei (NeuN)-positive cells in HDG was decreased after photothrombotic ischemia in TLR2 KO mice compared to that in WT mice. The survival rate of cells in HDG was decreased in TLR2 KO mice compared to that in WT mice. In contrast, the number of cleaved-caspase 3 (apoptotic marker) and the number of GFAP (glia marker)/BrdU double-positive cells in TLR2 KO mice were higher than that in WT mice. These results suggest that TLR2 can promote adult neurogenesis from neural stem cell of hippocampal dentate gyrus through increasing proliferation, differentiation, and survival from neural stem cells after ischemic injury of the brain.

• Journal of electromagnetic engineering and science
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• 제15권3호
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• pp.173-180
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• 2015

To explore the effects of radiofrequency electromagnetic field on the fate of neuronal cells, we investigated whether exposure to 915 MHz radiofrequency identification (RFID) caused morphological changes in neuronal cells in rat hippocampal dentate gyrus (DG). A reverberation chamber was used as a whole-body RFID exposure system. Rats were assigned to two groups: sham- and RFID-exposed groups. Rats in the RFID-exposed group were exposed to RFID at 4 W/kg specific absorption rate (SAR) for 8 hours daily, 5 days per week, for 2 weeks. Morphological evaluation of DG was performed using immunohistochemistry with doublecortin (DCX) as a neuronal precursor cell marker and neuronal nuclei (NeuN) as a mature neuronal cell marker. No significant morphological changes in DCX+ or NeuN+ cells in the DG of RFID-exposed rats were observed. These results suggest that RFID exposure induces no significant change in DCX+ neuronal precursor or NeuN+ neuronal cells in DG of rats.

• 동의생리병리학회지
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• 제19권3호
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• pp.647-655
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• 2005

This study demonstrated anti-oxidative and neuroprotective effects of Rhei Rhizoma. Anti-oxidative effects were studied on BV-2 microglia cells damaged by $H_2O_2$ and nitric oxide. Neuroprotective effects were studied by using oxygen/glucose deprivation of the organotypic hippocampal slice cultures. The results obtained are as follows; The groups treated with 0.5 and 5 mg/ml of Puerariae Radix revealed significant decreases of neuronal cell death area and cell death area percentages in CA1 region of ischemic damaged hippocampus cultures during whole 48 hours of the experiment. The group treated with 50 mg/ml of Puerariae Radix demonstrated decreases of neuronal cell death area and cell death area percentages in CA1 region, but these were not significant statistically. The groups treated with 0.5 and 5 mg/ml of Puerariae Radix revealed significant decreases of neuronal cell death area and cell death area percentages in dentate gyrus of ischemic damaged hippocampus cultures during whole 48 hours of the experiment. The group treated with 50 mg/ml of Puerariae Radix demonstrated decreases of neuronal cell death area and cell death area percentages in dentate gyrus, but these were not significant statistically. The groups treated with 0.5 and 5 mg/ml of Puerariae Radix revealed significant decreases of TUNEL-positive cells in both CA1 region and dentate gyrus of ischemic damaged hippocampus cultures. The group treated with 50 mg/ml of Puerariae Radix demonstrated significant decrease of TUNEL-positive cells in CA1 region, but not in dentate gyrus of ischemic damaged hippocampus. The groups treated with 0.5 and 5 mg/ml of Puerariae Radix revealed significant decreases of LDH concentrations in culture media of ischemic damaged hippocampus cultures. The group treated with 50 mg/ml of Puerariae Radix demonstrated decrease of LDH concentrations in culture media, but it was not significant statistically. The groups treated with 0.5 and 5 mg/ml of Puerariae Radix revealed significant increases of cell viabilities of BV-2 microglia cells damaged by $H_2O_2$. The group treated with 50 mg/ml of Puerariae Radix demonstrated increase of cell viability of BV-2 microglia cells, but it was not significant statistically. The group treated with 0.5 mg/ml of Puerariae Radix revealed significant increase of cell viability of BV-2 microglia cells damaged by nitric oxide. The groups treated with 5 and 50 mg/ml of Puerariae Radix demonstrated increases of cell viabilities of BV-2 microglia cells, but these were not significant statistically. These results suggested that Puerariae Radix revealed neuroprotective effects through the control effect of apoptosis and oxidative damages.

• 한방재활의학과학회지
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• 제21권2호
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• pp.1-13
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• 2011

Objectives : We investigated the effect of Haein-tang(Hairen-tang) on short-term memory and apoptosis in dentate gyrus of the gerbils with transient global ischemia. Methods : For the induction of cerebral ischemia model in mice, common carotid arteries of gerbils were occluded with aneurysm clips for 5 min. One day after operation, Haein-tang(Hairen-tang) was administrated orally injected once a day for 15 consecutive days. Gerbils were randomly divided into four group(n=10 in each group): sham-operation group, ischemia-induction group, ischemia-induction and 50 mg/kg Haein-tang(Hairen-tang)-treated group, ischemia-induction and 100 mg/kg Haein-tang(Hairen-tang)-treated group, and ischemia-induction and 200 mg/kg Haein-tang(Hairen-tang)-treated group. The effect of Haein-tang(Hairen-tang) on memory function was investigated by using step-down avoidance task. Apoptosis was confirmed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) staining and immunohistochemistry for caspase-3. Western blot analysis for the expressions of Bax and Bcl-2 protein was also conducted. Results : 1. Haein-tang extract significantly enhanced short-term memory in step-down avoidance task and 100 mg/kg, 200 mg/kg Haein-tang-treated group. 2. Haein-tang extract significantly suppressed TUNEL-positive cells after transient global ischemia and 50 mg/kg, 100 mg/kg, 200 mg/kg Haein-tang-treated group. 3. Haein-tang extract significantly increased caspase-3 positive cells in the hippocampal dentate gyrus after transient global ischemia and 50 mg/kg, 100 mg/kg, 200 mg/kg Haein-tang-treated group. 4. Haein-tang extract significantly decreased Bax protein expressions in the hippocampus after transient global ischemia and 100 mg/kg, 200 mg/kg, Haein-tang-treated group. Haein-tang extract significantly increased Bcl-2 protein expressions in the hippocampal dentate gyrus after transient global ischemia and 50 mg/kg, 100 mg/kg, 200 mg/kg, Haein-tang-treated group. Haein-tang extract significantly decreased Ratio of Bax protein to Bcl-2 protein in the hippocampus after transient global ischemia and 100 mg/kg, 200 mg/kg Haein-tang-treated group. Conclusions : While Haein-tang(Hairen-tang) treatment improved short-term memory by suppressing on ischemia-induction apoptosis. In the present study, Haein-tang(Hairen-tang) shows protective effect on transient global ischemia.

• The Korean Journal of Physiology and Pharmacology
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• 제21권6호
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• pp.695-702
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• 2017

The sustained tonic currents ($I_{tonic}$) generated by ${\gamma}$-aminobutyric acid A receptors ($GABA_{A}Rs$) are implicated in diverse age-dependent brain functions. While various mechanisms regulating $I_{tonic}$ in the hippocampus are known, their combined role in $I_{tonic}$ regulation is not well understood in different age groups. In this study, we demonstrated that a developmental increase in GABA transporter (GAT) expression, combined with gradual decrease in $GABA_AR{\alpha}_5$ subunit, resulted in various $I_{tonic}$ in the dentate gyrus granule cells (DGGCs) of preadolescent rats. Both GAT-1 and GAT-3 expression gradually increased at infantile ($P_{6-8}$ and $P_{13-15}$) and juvenile ($P_{20-22}$ and $P_{27-29}$) stages, with stabilization observed thereafter in adolescents ($P_{34-36}$) and young adults ($P_{41-43}$). $I_{tonic}$ facilitation of a selective GAT-1 blocker (NO-711) was significantly less at $P_{6-8}$ than after $P_{13-15}$. The facilitation of $I_{tonic}$ by SNAP-5114, a GAT-3 inhibitor, was negligible in the absence of exogenous GABA at all tested ages. In contrast, $I_{tonic}$ in the presence of a nonselective GAT blocker (nipecotic acid, NPA) gradually decreased with age during the preadolescent period, which was mimicked by $I_{tonic}$ changes in the presence of exogenous GABA. $I_{tonic}$ sensitivity to L-655,708, a $GABA_AR{\alpha}_5$ subunit inverse agonist, gradually decreased during the preadolescent period in the presence of NPA or exogenous GABA. Finally, Western blot analysis showed that the expression of the $GABA_AR{\alpha}_5$ subunit in the dentate gyrus gradually decreased with age. Collectively, our results suggested that the $I_{tonic}$ regulation of altered GATs is under the final tune of $GABA_AR{\alpha}_5$ subunit activation in DGGCs at different ages.

• 생명과학회지
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• 제17권3호통권83호
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• pp.305-311
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• 2007

글루코코르티코이드는 해마 조직에서 대사, 스냅신 형성, apoptosis, 신경세포 생성과 세포에 있어서 수지상의 형태에 영향을 준다. 글루코코르티코이드 호르몬에 의한 해마조직의 생리학적 조절을 이해하기 위하여, CA3와 DG (dentate gyrus)에서 유전자 발현에 대하여 조사하였다. Lewis 쥐에 9.5mg의 코르티코스테론 알약 또는 플라시보 알약을 20일 동안 처리한 후에 올리고머 유전자 칩을 이용하여 유전자 발현을 조사 하였다 (Rat Neurobiology U34 Arrays, Affymetrix). 플라시보 알약을 처리한 쥐에서 32 유전자들이 DG보다 CA3에서 발현이 높았으며, 3개 유전자는 CA3보다 DG에서 높은 발현을 보였다. 코르티코스테론 호르몬 처리에 의한 해마조직의 유전자 발현 형태는 해부학적 구조의 차이를 보였다. 특히, CA3에서 6개의 유전자와 DG에서 41 개의 유전자가 호르몬에 의하여 조절 받았으며, 이중 43개의 유전자가 상승 발현하였으며, 4개의 유전자가 하강 발현 하였다. 이들 유전자를 기능에 의해 분류하면, 13개의 신경전달물질관련 유전자, 5개의 이온채널,4개의 전사인자, 3개의 neurotrophic인자, 1개의 각 사이토카인과 apoptosis관련 유전자, 그리고 5개의 스냅신형성관련 유전자가 해마조직에서 발현의 변화를 보였다. 특히, 스트레스 호르몬에 의하여 CA3에서 BDNF의 감소를 볼 수 있었다. 이러한 결과는 호르몬에 의하여 해마구조의 생리학적인 다양성을 내포 하고 있다.

• The Journal of Korean Physical Therapy
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• 제15권3호
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• pp.295-345
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• 2003

This study investigated activation of cerebral cortex in patients with hemiplegia that was caused by neural damage. Key-point control movement therapy of Bobath was performed for 9 weeks in 3 subjects with hemiplegia and fMRI was used to compare and analyze activated degree of cerebral cortex in these subjects. fMRI was conducted using the blood oxygen level-dependent(BOLD) technique at 3.0T MR scanner with a standard head coil. The motor activation task consisted of finger flexion-extension exercise in six cycles(one half-cycles = 8 scans = $3\;sec{\times}\;8\;=\;24\;sec$). Subjects performed this task according to visual stimulus that sign of right hand or left hand twinkled(500ms on, 500ms off). After mapping activation of cerebral motor cortex on hand motor function, below results were obtained. 1. Activation decreased in primary motor area, whereas it increased in supplementary motor area and visual association area(p<.001). 2. Activation was observed in bilateral medial frontal gyrus, middle frontal gyrus of left cerebrum, inferior frontal gyrus, inter-hemispheric, fusiform gyrus of right cerebrum, superior parietal lobule of parietal lobe and precuneus in subjedt 1, parahippocampal gyrus of limbic lobe and cingulate gyrus in subject 2, and inferior frontal gyrus of right frontal lobe, middle frontal gyrus, and inferior parietal lobule of left cerebrum in subject 3 (p<.001). 3. Activation cluster extended in declive of right cellebellum posterior lobe in subject 1, culmen of anterior lobe and declive of posterior lobe in subject 2, and dentate gyrus of anterior lobe, culmen and tuber of posterior lobe in subject 3 (p<.001). In conclusion, these data showed that Key-point control movement therapy of Bobath after stroke affect cerebral cortex activation by increasing efficiency of cortical networks. Therefore mapping of brain neural network activation is useful for plasticity and reorganization of cerebral cortex and cortico-spinal tract of motor recovery mechanisms after stroke.

• Molecules and Cells
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• 제26권2호
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• pp.186-192
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• 2008

NELL2, a neural tissue-enriched protein, is produced in the embryo, and postembryonically in the mammalian brain, with a broad distribution. Although its synthesis is required for neuronal differentiation in chicks, not much is known about its function in the adult mammalian brain. We investigated the distribution of NELL2 in various regions of the adult rat brain to study its potential functions in brain physiology. Consistent with previous reports, NELL2-immunoreactivity (ir) was found in the cytoplasm of neurons, but not in glial fibrillary acidic protein (GFAP)-positive glial cells. The highest levels of NELL2 were detected in the hippocampus and the cerebellum. Interestingly, in the cerebellar cortex NELL2 was observed only in the GABAergic Purkinje cells not in the excitatory granular cells. In contrast, it was found mainly in the hippocampal dentate gyrus and pyramidal cell layer that contains mainly glutamatergic neurons. In the dentate gyrus, NELL2 was not detected in the GFAP-positive neural precursor cells, but was generally present in mature neurons of the subgranular zone, suggesting a role in this region restricted to mature neurons.