• Title/Summary/Keyword: Ischemic brain injury

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Functional recovery after transplantation of mouse bone marrow-derived mesenchymal stem cells for hypoxic-ischemic brain injury in immature rats (저산소 허혈 뇌 손상을 유발시킨 미성숙 흰쥐에서 마우스 골수 기원 중간엽 줄기 세포 이식 후 기능 회복)

  • Choi, Wooksun;Shin, Hye Kyung;Eun, So-Hee;Kang, Hoon Chul;Park, Sung Won;Yoo, Kee Hwan;Hong, Young Sook;Lee, Joo Won;Eun, Baik-Lin
    • Clinical and Experimental Pediatrics
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    • v.52 no.7
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    • pp.824-831
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    • 2009
  • Purpose : We aimed to investigate the efficacy of and functional recovery after intracerebral transplantation of different doses of mouse mesenchymal stem cells (mMSCs) in immature rat brain with hypoxic-ischemic encephalopathy (HIE). Methods : Postnatal 7-days-old Sprague-Dawley rats, which had undergone unilateral HI operation, were given stereotaxic intracerebral injections of either vehicle or mMSCs and then tested for locomotory activity in the 2nd, 4th, 6th, and 8th week of the stem cell injection. In the 8th week, Morris water maze test was performed to evaluate the learning and memory dysfunction for a week. Results : In the open field test, no differences were observed in the total distance/the total duration (F=0.412, P=0.745) among the 4 study groups. In the invisible-platform Morris water maze test, significant differences were observed in escape latency (F=380.319, P<0.01) among the 4 groups. The escape latency in the control group significantly differed from that in the high-dose mMSC and/or sham group on training days 2-5 (Scheffe's test, P<0.05) and became prominent with time progression (F=6.034, P<0.01). In spatial probe trial and visible-platform Morris water maze test, no significant improvement was observed in the rats that had undergone transplantation. Conclusion : Although the rats that received a high dose of mMSCs showed significant recovery in the learning-related behavioral test only, our data support that mMSCs may be used as a valuable source to improve outcome in HIE. Further study is necessary to identify the optimal dose that shows maximal efficacy for HIE treatment.

Hybrid Two-Dimensional Proton Spectroscopic Imaging of Pediatric Brain: Clinical Application (소아 뇌에서의 혼성 이차원 양성자자기공명분광법의 임상적 응용)

  • Sung Won Youn;Sang Kwon Lee;Yongmin Chang;No Hyuck Park;Jong Min Lee
    • Investigative Magnetic Resonance Imaging
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    • v.6 no.1
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    • pp.64-72
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    • 2002
  • Purpose : To introduce and demonstrate the advantages of the new hybrid two-dimensional (2D) proton spectroscopic imaging (SI) over the single voxel spectroscopy (SVS) and conventional 2D SI in the clinical application of spectroscopy for pediatric cerebral disease. Materials and Methods : Eighty-one hybrid 2D proton spectroscopic imaging was performed in 79 children (36 normal infants and children, 10 with hypoxic-ischemic injury, 20 with toxic-metabolic encephalopathy, seven with brain tumor, three with meningoencephalitis, one with neurofibromatosis, one with Sturge-Weber syndrome and one with lissencephaly) ranging in age from the third day of life to 15 years. In adult volunteers (n=5), all three techniques including hybrid 2D proton SI, SVS using PRESS sequence, and conventional 2D proton SI were performed. Both hybrid 2D proton SI and SVS using PRESS sequence were performed in clinical cases (n=). All measurements were performed with a 1.5-T scanner using standard head quadrature coil. The 16$\times$16 phase encoding steps were set on variable field of view (FOV) depending on the size of the brain. The hybrid volume of interest inside FOV was set as $75{\times}75{\times}15{\;}\textrm{mm}^3$ or smaller to get rid of unwanted fat signal. Point-resolved spectroscopy (TR/TE=1,500 msec/135 or 270msec) was employed with standard chemical shift selective saturation (CHESSI pulses for water suppression. The acquisition time and spectral quality of hybrid 2D proton SI were compared with those of SVS and conventional 2D proton SI. Results : The hybrid 2D proton SI was successfully conducted upon all patients.

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Anti-apoptotic and neuroprotective effects of acupuncture techniques of tonification or sedation at HT9${\cdot}$LR1, HT3${\cdot}$KI10 on focal brain ischemic injury induced by intraluminal filament insertion in rats (심정격(心正格) 혈위(穴位)(소충(少衝)${\cdot}$대돈(大敦), 소해(少海)${\cdot}$음곡(陰谷))에 대한 영수(迎隨) 및 염전(捻轉) 보사(補瀉) 침자(鍼刺)가 국소 뇌허혈 유발 흰쥐의 항뇌세포고사와 신경보호 효과에 미치는 영향)

  • Byun, Jeong-Yun;Youn, Dae-Hwan;Na, Chang-Su
    • Korean Journal of Acupuncture
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    • v.25 no.1
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    • pp.229-246
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    • 2008
  • Objectives : Acupoints of LR1(Dadun)${\cdot}$HT9(Shaochong), KI10(Yingu)${\cdot}$HT3(Shaohai) are used as controlling the diseases from heart problems. Especially, when they are used, tonification or sedation techniques method is taken as a controlling the medication for an early stroke in the Korean medicine. So the aim of this study is to investigate the anti-apoptotic and neuroprotective effects of Acupuncture techniques of tonification or sedation at LR1${\cdot}$HT9, KI10${\cdot}$HT3 on the focal ischemia induced by intraluminal filament insertion in rats. Materials and Methods : The focal ischemia was induced by intraluminal filament insertion into middle cerebral artery. The animals were divided into five groups (n=7 in each group) : Control group, no therapy group after ischemia induced; AT-1; acupuncture therapy group at LR1${\cdot}$HT9, KI10${\cdot}$HT3 after ischemia-induced. AT-2; acupuncture therapy at right LR1, HT9(forward direction), KI10${\cdot}$HT3(opposite direction) inserting to the direction of route of the each meridian. AT3; acupuncture therapy at right LR1, HT9(twirling forward with the thumb of right hand 9 times), KI10${\cdot}$HT3(twirling forward with the forefinger of right hand 6 times) AT-4; acupuncture therapy at right LR1, HT9(forward direction, twirling forward with the thumb of right hand 9 times), KI10${\cdot}$HT3(opposite direction, twirling forward with the forefinger of right hand 6 times) inserting to the direction of route of the each meridian. The anti-apoptotic and neuroprotective effects of Acupuncture techniques of tonification or sedation at LR1, HT9, KI10${\cdot}$HT3 were observed by Bax, Bcl-2, mGluR5, Cytochrome c, Cresyl violet and ChAT-stain. Results : The intensity of Bax and Bax/Bcl-2 ratio were increased in ACU-2 and ACU-4 group but decreased in ACU-3 group. The intensity of mGluR5 was increased in ACU-1, ACU-2, ACU-3 and ACU-4 group. The intensity of cytochrome c was decreased in ACU-3 and ACU-4 group. The density of neurons stained by Cresyl violet and ChAT were increased in ACU-1, ACU-3 and ACU-4 group. Conclusions : Our study suggests that acupuncture therapy of tonification at LR1, HT9 by twirling forward with the thumb of right hand 9times, sedation at KI10${\cdot}$HT3 by twirling forward with the forefinger of right hand 6 times after perpendicularly inserting needle shows anti-apoptotic and neuroprotective effects on cholinergic neuron in focal cerebral ischemia of the stroke in rats.

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Effects of BCL herbal acupuncture into Choksamni(ST36) on focal brain ischemic injury induced by intraluminal filament insertion in the rats (족삼리(足三里)에 시술(施術)된 죽력(竹歷) 약침(藥鍼)이 Intraluminal Filament 삽입술(揷入術)에 의하여 유발(誘發)된 백서(白鼠)의 허혈성(虛血性) 국소(局所) 뇌손상(腦損傷)에 미치는 영향(影響))

  • Youn, Dae-Hwan;Lee, Bom-Bi;Shim, In-Sop;Na, Chang-Su
    • Korean Journal of Acupuncture
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    • v.22 no.2
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    • pp.25-41
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    • 2005
  • Objectives : Bambusae Caulis in Liquamen(BCL) has been used to medication for early stroke in the Oriental Medicine. So this study was planned to investigate the effects of BCL on the focal ischemia-induced by intraluminal filament insertion in the rats. Materials and methods: The focal ischemia was induced by Intraluminal Filament insertion into middle cerebral artery. BCL herbal acupuncture at ST36 was carried out during 3 weeks after focal ischemia-induced. Eight-arm radial maze was used for the behavioral task and neuroprotective effect of BCL acupuncture was observed by Cresyl violet, AchE, ChAT-stain Results : The error rate in the eight-arm radial maze task was significantly decreased in BCL1(0.89mg/kg) herbal acupuncture group compared to control group on 3,4,5days, compared to saline acupuncture group on 3,5days. The rate of correct choice was significantly increased in saline acupuncture, BCL1 herbal acupuncture group, BCL2(0.089mg/kg) herbal acupuncture groups compared to control group. The density of neurons in the hippocampal CA1 was the most increased in BCL1 herbal acupuncture group compared to the others. The density of AchE in the hippocampal CA1 was significantly increased in BCL1 herbal acupuncture, BCL2 herbal acupuncture groups compared to control group, and in BCL2 herbal acupuncture groups increased compared to saline acupuncture, control groups. The density of ChAT in the hippocampal CA1 was significantly increased in BCLl herbal acupuncture group compared to saline acupuncture, control groups. Conclusions : These results suggest that BCL herbal acupuncture could be used as a medication for controlling the early stroke.

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Effects of Cnidium of ficinale(CO) extracts through administrated by means of oral and herbal acupuncture method at GB2l acupoint on focal ischemic brain injury induced by MCAO in rats (천궁(川芎)의 구강투여(口腔投與) 및 약침시술(藥鍼施術)이 흰쥐 MCAO로 유발된 국소뇌허혈(局所腦虛血)에 대(對)한 콜린성 신경보호효과(神經保護效果) 연구(硏究))

  • Kim, Kyung-Sun;Youn, Dae-Hwan;Hong, Seok;Na, Chang-Su
    • Korean Journal of Acupuncture
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    • v.22 no.3
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    • pp.137-156
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    • 2005
  • Objectives : Cnidium officinale(CO) has been used for medication for stroke in the Oriental Medicine. So this study was planned to investigate the effects of CO on the focal ischemia-induced by Middle Cerebral Artery Occlusion(MCAO) in rats Materials and methods : The focal ischemia was induced by MCAO. CO extracts through oral administration and herbal acupuncture at GB2l was carried out during 3 weeks after focal ischemia-induced. Eight-arm radial maze was used for the behavioral task. For the neuroprotective effect of CO, we investigated AchE, ChAT, and NGF-expression by immnohistochemical method. Results : The error rate in the eight-arm radial maze task was significantly decreased in normal group compared to control group on 1-6days, OA-CO1(CO oral administration, 0.8g/kg) group on 1-6days, OA-CO2(CO oral administration, 1.6g/kg) group on 1-3,5,6days, HA-CO1(CO herbal acupuncture, 0.016g/kg) group on 2,3,6days, HA-CO2(CO herbal acupuncture, 0.008g/kg) group on 1-3,5,6days. The rate of correct choice was significantly increased in OA-CO1, HA-CO2. The density of neurons in the hippocampal CA1 was the most increased in OA-CO1, HA-CO1, HA-CO2. The density of ChAT in the hippocampal CA1 was increased in OA-CO1, HA-CO2. The density of ChAT in the hippocampal CA1 was significantly increased in OA-CO1, HA-CO2. The density of NGE in the hippocampal CAI was significantly increased in OA-CO1, OA-CO2, HA-CO2. Conclusions : These results suggest that CO oral administration with 0.8g/kg and CO herbal acupuncture with 0.008g/kg might be used as a regulator of cell death of cholinergic system induced by stroke.

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Comparison of Effects between Alteplase and Pamiteplase on MMPs Regulation (Alteplase와 pamiteplase에 의한 MMPs 조절 효과 비교)

  • Jung, Jae-Chang;Lee, Sun-Ryung
    • Journal of Life Science
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    • v.17 no.7 s.87
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    • pp.1019-1022
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    • 2007
  • Thrombolytic therapy with tissue plasminogen activator (tPA) can improve the clinical outcome of ischemic stroke patients. However, its clinical application is limited by narrow therapeutic time windows and elevated risks of cerebral hemorrhage and brain injury. In part, these effects of tPA has been related to matrix metalloproteinase-9 (MMP-9) dysregulation. Here, we investigate that the effects of alteplase (tPA with short half-life) and pamiteplase (a modified tPA with long half-life) on the MMP-9 regulation in neurovascualr unit. The total levels of MMP-2 and MMP-9 in neuronal cells are lower than astrocytes. Alteplase (1-10 ${\mu}g/ml$) induced upregulation of MMP-2 and MMP-9 in rat cortical neurons and astrocytes, respectively. Whereas pamiteplase in a wide range of dose did not affect the MMP-2 and MMP-9 responses in both of cells. These results suggest that pamiteplase with long half-life can be provided as a agent that overcome the side effects of alteplase.

Anti-apoptotic and neuroprotective effects of acupuncture techniques of tonification or sedation at LR3 on focal brain ischemic injury induced by intraluminal filament insertion in rats (태위(太衝)(LR3)에 대한 영수(迎隨)및 염전보사(捻轉補瀉)가 intraluminal filament 삽입술(揷入術)에 의하여 유발(誘發)된 백서(白鼠)의 focal ischemia에 미치는 영향(影響))

  • Park, Jong-Seung;Na, Chang-Su;Cho, Myeng-Rae;Jung, Yeon-Jin;Jeong, Ji-Yeon;Kim, Won-Jae;Choi, Chan-Hun;Youn, Dae-Hwan
    • Korean Journal of Acupuncture
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    • v.23 no.3
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    • pp.81-98
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    • 2006
  • Objectives : Acupuncture using a tonification or sedation techniques method is used as a controlling the medication for an early stroke in the Korean medicine. LR3 has indicatons of headache, vertigo, facial paralysis, apoplexy, epiepsy as the source acupoint of a liver meridian. So this study is aims to investigate the anti-apoptotic and neuroprotective effects of acupuncture on the focal ischemia induced by intraluminal filament insertion in rats. Methods : The focal ischemia was induced by intraluminal filament insertion into middle cerebral artery. The animals were divided into seven groups (n=8 in each group) : Normal, intactness group; Conrol group, no therapy group after being ischemia induced; MA-l, acupuncture perpendicularly without Tonification or Sedation techniques at LR3 after being ischemia induced; MA-2, acupuncture obliquely towards the knee at LR3 after being ischemia induced; MA-3, acupuncture obliquely towards the toe at LR3 after being ischemia induced; MA-4, acupuncture obliquely towards the knee and rotate 9 times in a clockwise direction at LR3 after being ischemia induced; MA-5, acupuncture obliquely towards the toe and rotate 6 times in a counterclockwise direction at LR3 after being ischemia induced. The anti-apoptotic and neuroprotective effects of Acupuncture techniques of tonification or sedation at LR3 are observed by mGluR5, Bax, Cresyl violet, ChAT-stain and NGF. Results : The intensity of mGluR5 and the density of ChAT was increased in MA-1 group. The intensity of Bax was decreased in MA-3, MA-4 group. The density of neurons stained by Cresyl violet and ChAT was increased in MA-2, MA-3, MA-4, MA-5 group. The density of neurons stained by NGF was only increased in MA-4 group. Conclusions : Our study suggests that acupuncture perpendicularly without Tonification or Sedation techniques and obliquely towards the knee and rotate 9 times in a clockwise direction(Tonifying technique) at LR3 after being ischemia induced at LR3 shows anti-apoptotic and neuroprotective effects on cholinergic neuron in focal cerebral ischemia of the stroke in rats.

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Effects of acupuncture at the $LU8{\cdot}K17$ on Anti-apoptotic cell death and neuroprotection in Rat hippocampus following focal brain ischemic injury induced by Intraluminal Filament insertion in Rats (직자(直刺), 영수(迎隨) 및 염전수기법(捻轉手技法)에 따라 시행한 경거(經渠)${\cdot}$복류(復溜) 침자(鍼刺)가 중대뇌동맥(中大腦動脈) 폐새(閉塞)에 의하여 유발(誘發)된 국소(局所) 뇌허혈(腦虛血) 백서(白鼠) hippocampus의 항세포자멸사(抗細胞自滅死) 및 복경보호(福經保護)에 미치는 영향(影響))

  • Youn, Dae-Hwan;Byun, Jeng-Yun;Choi, Chan-Hun;Baek, Jin-Ung;Jeong, Ji-Yeon;Jung, Yeon-Jin;Na, Chang-Su
    • Korean Journal of Acupuncture
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    • v.24 no.3
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    • pp.205-221
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    • 2007
  • Objectives : Aims of this study is to investigate the effects of $LU8{\cdot}KI7$ in rat induced by experimental focal ischemia. Materials and methods : The focal ischemia was induced by intraluminal filament insertion into middle cerebral artery. The groups divided into 6groups, control; no therapy group after ischemia-induced, AT1; acupuncture therapy group at $LU8{\cdot}KI7$ after ischemia-induced, AT2; acupuncture therapy at $LU8{\cdot}KI7$ bilaterally and the needle was twirled and rotated forward with the thumb of the right hand 9times, AT3; acupuncture therapy at $LU8{\cdot}KI7$ bilaterally and the needle was twirled and rotated forward with the forefinger of the right hand 9times, AT4; acupuncture therapy at$LU8{\cdot}KI7$ bilaterally and the needle was inserted to the direction following the flowing route of the meridian(digital direction), AT5; acupuncture therapy at $LU8{\cdot}KI7$ bilaterally, the needle was inserted to the direction following the flowing route of the meridian(digital direction) and the needle was twirled and rotated forward with the thumb of the right hand 9times. Acupuncture therapy was carried out 7times during 2weeks after focal ischemia-induced. The anti-apoptotic and neuroprotective effects of acupuncture are observed by Bax, Bcl-2, mGluR5, cytochrome c, Cresyl violet and ChAT-stain. Results : The intensity of Bax was decreased in AC1, AC4, AC5 group, was increased in AC2, AC3 group. The intensity of Bcl-2 was increased in AC2, AC3, AC4, AC5 group. The intensity of mGluR5 was decreased in AC1 group, was increased in AC4, AC5 group. The intensity of Cytochrome c was increased in ACI, AC2 group, was decreased in AC4, AC5 group. The density of neurons stained by Cresyl violet was increased in all group without control group. The density of ChAT was increased in AC2, ACS group. Conclusions : Our study suggests that AC5 group show anti-apoptotic and neuroprotective effects on cholinergic neuron in focal cerebral ischemia of the stroke in rats.

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Thioredoxin Peroxidase Manifestation in Radiation-Induced White Rat Lung Tissues (방사선 조사후 손상된 백서 폐조직에서의 Thioredoxin Peroxidase의 발현)

  • Chong, Seong-Cheoll;Park, Joon-Seong;Park, Jee-Won;Lee, Sun-Min;Park, Kwang-Joo;Hwang, Sung-Chul;Lee, Yi-Hyeong;Hahn, Myung-Ho;Oh, Young-Taek;Kim, Hyung-Joong
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.5
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    • pp.650-659
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    • 1999
  • Background/Aims: It is well recognized that all aerobic cells have the protective mechanisms in order to minimize the tissue damage induced by various reactive oxygen species(ROS). Thioredoxin peroxidase(TPX) which has been recently identified and characterized functions to convert peroxide to water. The protein is also found in various subtypes(TPX-A & B, MER5, HS22 and HORF-06) and is known to be ubiquitous in most human cells. Especially, ischemic brain injuries, partial hepatectomy and radiation induced DNA damages. In treating lung cancer, radiation therapy has a major place in the local control and the relief of symptoms, but radiation induced free radical injury and resulting pulmonary fibrosis has been the major drawback of the therapy. However, little is known about the protective mechanisms and biologic modulations against radiation-induced tissue damages. Methods: Eighteen mice were divided into six groups, 3 in each group, and fifteen had received 900cGy of radiation. The mice were sacrificed according to the pre determined time schedule; immediate, 1, 2, 3 and 6 weeks after irradiation. Extracts were made from the lungs of each mice, Western blot analysis of various subtypes of TPX were done after SDS-P AGE. Examination of H & E stained slides from the same irradiated specimens and the control specimens were also performed. Results: No difference in the intensity of the immunoreactive bands in the irradiated lung samples of the mice compared to the unirradiated control was observed regardless of the time intervals, although H & E examination of the sample specimens demonstrated progressive fibrotic changes of the irradiated lung samples. Conclusion: In conclusion, according to our data, it is suggested that various thioredoxin peroxidase subtypes and catalase which are known to be increased in many repair processes may not be involved in the repair of the radiation injury to the lung and subsequent fibrosis.

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Microarray Analysis of Gene Expression in Rat Glioma after Ethanol Treatment (에탄올 처리에 의한 흰쥐 신경아교종(Glioma) 세포에서의 유전자 발현 - DNA 칩을 이용한 분석 -)

  • Lee, So Hee;Oh, Dong-Yul;Han, Jin-Hee;Choi, Ihn-Geun;Jeon, Yang-Whan;Lee, Joon-Noh;Lee, Tae Kyung;Jeong, Jong-Hyun;Jung, Kyung Hwa;Chai, Young-Gyu
    • Korean Journal of Biological Psychiatry
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    • v.14 no.2
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    • pp.115-121
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    • 2007
  • Objetives : Identification of target genes for ethanol in neurons is important for understanding its molecular and cellular mechanism of action and the neuropathological changes seen in alcoholics. The purpose of this study is to identify of altered gene expression after acute treatmet of ethanol in rat gliom cells. Methods : We used high density cDNA microarray chip to measure the expression patterns of multiple genes in cultured rat glioma cells. DNA microarrays allow for the simultaneous measurement of the expression of several hundreds of genes. Results : After comparing hybridized signals between control and ethanol treated groups, we found that treatment with ethanol increased the expression of 15 genes and decreased the expression of 12 genes. Upregulated genes included Orthodenticle(Drosophila) homolog 1, procollagen type II, adenosine A2a receptor, GATA bindning protein 2. Downregulated genes included diacylglycerol kinase beta, PRKC, Protein phosphatase 1, clathrin-associated protein 17, nucleoporin p58, proteasome. Conclusion : The gene changes noted were those related to the regulation of transcription, signal transduction, second messenger systems. modulation of ischemic brain injury, and neurodengeneration. Although some of the genes were previously known to be ethanol responsive, we have for the most part identified novel genes involved in the brain response to ethanol.

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