Postischemic gene transfer of interleukin-10 protects against both focal and global brain ischemia

Hiroaki Ooboshi, Setsuro Ibayashi, Takashi Shichita, Yasuhiro Kumai, Junichi Takada, Tetsuro Ago, Shuji Arakawa, Hiroshi Sugimori, Masahiro Kamouchi, Takanari Kitazono, Mitsuo Iida

研究成果: ジャーナルへの寄稿記事

137 引用 (Scopus)

抄録

Background - Gene therapy may be a promising approach for treatment of brain ischemia, although the efficiency of postischemic gene therapy is not established. Our goal in this study was to examine the effects of gene transfer of interleukin-10 (IL-10), an antiinflammatory cytokine, after induction of brain ischemia. Methods and Results - Brain ischemia was produced by either photochemical occlusion of distal middle cerebral artery for focal ischemia or bilateral carotid occlusion for global ischemia in spontaneously hypertensive rats. Adenoviral vectors encoding human IL-10 (AdIL10) or β-galactosidase (control) were injected into the lateral ventricle 90 or 60 minutes after focal or global ischemia. Five days after ischemia, IL-10, IL-1β, or tissue necrosis factor-α in the cerebrospinal fluid, infarct volume, infiltrations of leukocytes/macrophages in the infarct area, or hippocampal neuronal damages were determined. The transduced IL-10 was released to the cerebrospinal fluid from the ventricular wall and increased to 7623±2965 pg/mL 5 days after AdIL10 transfection. Cerebral blood flow during ischemia was not different between treatments in either focal or global ischemia. Brain infarction of the AdIL10 group was significantly smaller and infiltrations of leukocytes and macrophages were fewer in the IL-10 treatment than control. Hippocampal neurons after global ischemia were more preserved, and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling-positive cells were diminished by the IL-10 gene transfer with attenuated IL-1β and augmented tissue necrosis factor-α. Conclusions - Postischemic gene transfer of IL-10 into the lateral ventricle attenuated brain infarction and hippocampal damages, suggesting the promise for treatment of brain ischemia.

元の言語英語
ページ(範囲)913-919
ページ数7
ジャーナルCirculation
111
発行部数7
DOI
出版物ステータス出版済み - 2 22 2005

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Brain Ischemia
Interleukin-10
Ischemia
Genes
Brain Infarction
Lateral Ventricles
Thromboplastin
Interleukin-1
Genetic Therapy
Cerebrospinal Fluid
Cerebrovascular Circulation
Leukocytes
Necrosis
Macrophages
Galactosidases
DNA Nucleotidylexotransferase
Middle Cerebral Artery Infarction
In Situ Nick-End Labeling
Inbred SHR Rats
Biotin

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

これを引用

Postischemic gene transfer of interleukin-10 protects against both focal and global brain ischemia. / Ooboshi, Hiroaki; Ibayashi, Setsuro; Shichita, Takashi; Kumai, Yasuhiro; Takada, Junichi; Ago, Tetsuro; Arakawa, Shuji; Sugimori, Hiroshi; Kamouchi, Masahiro; Kitazono, Takanari; Iida, Mitsuo.

:: Circulation, 巻 111, 番号 7, 22.02.2005, p. 913-919.

研究成果: ジャーナルへの寄稿記事

Ooboshi, H, Ibayashi, S, Shichita, T, Kumai, Y, Takada, J, Ago, T, Arakawa, S, Sugimori, H, Kamouchi, M, Kitazono, T & Iida, M 2005, 'Postischemic gene transfer of interleukin-10 protects against both focal and global brain ischemia', Circulation, 巻. 111, 番号 7, pp. 913-919. https://doi.org/10.1161/01.CIR.0000155622.68580.DC
Ooboshi, Hiroaki ; Ibayashi, Setsuro ; Shichita, Takashi ; Kumai, Yasuhiro ; Takada, Junichi ; Ago, Tetsuro ; Arakawa, Shuji ; Sugimori, Hiroshi ; Kamouchi, Masahiro ; Kitazono, Takanari ; Iida, Mitsuo. / Postischemic gene transfer of interleukin-10 protects against both focal and global brain ischemia. :: Circulation. 2005 ; 巻 111, 番号 7. pp. 913-919.
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abstract = "Background - Gene therapy may be a promising approach for treatment of brain ischemia, although the efficiency of postischemic gene therapy is not established. Our goal in this study was to examine the effects of gene transfer of interleukin-10 (IL-10), an antiinflammatory cytokine, after induction of brain ischemia. Methods and Results - Brain ischemia was produced by either photochemical occlusion of distal middle cerebral artery for focal ischemia or bilateral carotid occlusion for global ischemia in spontaneously hypertensive rats. Adenoviral vectors encoding human IL-10 (AdIL10) or β-galactosidase (control) were injected into the lateral ventricle 90 or 60 minutes after focal or global ischemia. Five days after ischemia, IL-10, IL-1β, or tissue necrosis factor-α in the cerebrospinal fluid, infarct volume, infiltrations of leukocytes/macrophages in the infarct area, or hippocampal neuronal damages were determined. The transduced IL-10 was released to the cerebrospinal fluid from the ventricular wall and increased to 7623±2965 pg/mL 5 days after AdIL10 transfection. Cerebral blood flow during ischemia was not different between treatments in either focal or global ischemia. Brain infarction of the AdIL10 group was significantly smaller and infiltrations of leukocytes and macrophages were fewer in the IL-10 treatment than control. Hippocampal neurons after global ischemia were more preserved, and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling-positive cells were diminished by the IL-10 gene transfer with attenuated IL-1β and augmented tissue necrosis factor-α. Conclusions - Postischemic gene transfer of IL-10 into the lateral ventricle attenuated brain infarction and hippocampal damages, suggesting the promise for treatment of brain ischemia.",
author = "Hiroaki Ooboshi and Setsuro Ibayashi and Takashi Shichita and Yasuhiro Kumai and Junichi Takada and Tetsuro Ago and Shuji Arakawa and Hiroshi Sugimori and Masahiro Kamouchi and Takanari Kitazono and Mitsuo Iida",
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T1 - Postischemic gene transfer of interleukin-10 protects against both focal and global brain ischemia

AU - Ooboshi, Hiroaki

AU - Ibayashi, Setsuro

AU - Shichita, Takashi

AU - Kumai, Yasuhiro

AU - Takada, Junichi

AU - Ago, Tetsuro

AU - Arakawa, Shuji

AU - Sugimori, Hiroshi

AU - Kamouchi, Masahiro

AU - Kitazono, Takanari

AU - Iida, Mitsuo

PY - 2005/2/22

Y1 - 2005/2/22

N2 - Background - Gene therapy may be a promising approach for treatment of brain ischemia, although the efficiency of postischemic gene therapy is not established. Our goal in this study was to examine the effects of gene transfer of interleukin-10 (IL-10), an antiinflammatory cytokine, after induction of brain ischemia. Methods and Results - Brain ischemia was produced by either photochemical occlusion of distal middle cerebral artery for focal ischemia or bilateral carotid occlusion for global ischemia in spontaneously hypertensive rats. Adenoviral vectors encoding human IL-10 (AdIL10) or β-galactosidase (control) were injected into the lateral ventricle 90 or 60 minutes after focal or global ischemia. Five days after ischemia, IL-10, IL-1β, or tissue necrosis factor-α in the cerebrospinal fluid, infarct volume, infiltrations of leukocytes/macrophages in the infarct area, or hippocampal neuronal damages were determined. The transduced IL-10 was released to the cerebrospinal fluid from the ventricular wall and increased to 7623±2965 pg/mL 5 days after AdIL10 transfection. Cerebral blood flow during ischemia was not different between treatments in either focal or global ischemia. Brain infarction of the AdIL10 group was significantly smaller and infiltrations of leukocytes and macrophages were fewer in the IL-10 treatment than control. Hippocampal neurons after global ischemia were more preserved, and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling-positive cells were diminished by the IL-10 gene transfer with attenuated IL-1β and augmented tissue necrosis factor-α. Conclusions - Postischemic gene transfer of IL-10 into the lateral ventricle attenuated brain infarction and hippocampal damages, suggesting the promise for treatment of brain ischemia.

AB - Background - Gene therapy may be a promising approach for treatment of brain ischemia, although the efficiency of postischemic gene therapy is not established. Our goal in this study was to examine the effects of gene transfer of interleukin-10 (IL-10), an antiinflammatory cytokine, after induction of brain ischemia. Methods and Results - Brain ischemia was produced by either photochemical occlusion of distal middle cerebral artery for focal ischemia or bilateral carotid occlusion for global ischemia in spontaneously hypertensive rats. Adenoviral vectors encoding human IL-10 (AdIL10) or β-galactosidase (control) were injected into the lateral ventricle 90 or 60 minutes after focal or global ischemia. Five days after ischemia, IL-10, IL-1β, or tissue necrosis factor-α in the cerebrospinal fluid, infarct volume, infiltrations of leukocytes/macrophages in the infarct area, or hippocampal neuronal damages were determined. The transduced IL-10 was released to the cerebrospinal fluid from the ventricular wall and increased to 7623±2965 pg/mL 5 days after AdIL10 transfection. Cerebral blood flow during ischemia was not different between treatments in either focal or global ischemia. Brain infarction of the AdIL10 group was significantly smaller and infiltrations of leukocytes and macrophages were fewer in the IL-10 treatment than control. Hippocampal neurons after global ischemia were more preserved, and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling-positive cells were diminished by the IL-10 gene transfer with attenuated IL-1β and augmented tissue necrosis factor-α. Conclusions - Postischemic gene transfer of IL-10 into the lateral ventricle attenuated brain infarction and hippocampal damages, suggesting the promise for treatment of brain ischemia.

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JO - Circulation

JF - Circulation

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