Inhibition of soluble epoxide hydrolase after cardiac arrest/ cardiopulmonary resuscitation induces a neuroprotective phenotype in activated microglia and improves neuronal survival

Jianming Wang, Tetsuhiro Fujiyoshi, Yasuharu Kosaka, Jonathan D. Raybuck, K. Matthew Lattal, Mizuko Ikeda, Paco S. Herson, Ines P. Koerner

研究成果: ジャーナルへの寄稿記事

15 引用 (Scopus)

抄録

Cardiac arrest (CA) causes hippocampal neuronal death that frequently leads to severe loss of memory function in survivors. No specific treatment is available to reduce neuronal death and improve functional outcome. The brain's inflammatory response to ischemia can exacerbate injury and provides a potential treatment target. We hypothesized that microglia are activated by CA and contribute to neuronal loss. We used a mouse model to determine whether pharmacologic inhibition of the proinflammatory microglial enzyme soluble epoxide hydrolase (sEH) after CA alters microglial activation and neuronal death. The sEH inhibitor 4-phenylchalcone oxide (4-PCO) was administered after successful cardiopulmonary resuscitation (CPR). The 4-PCO treatment significantly reduced neuronal death and improved memory function after CA/CPR. We found early activation of microglia and increased expression of inflammatory tumor necrosis factor (TNF)- and interleukin (IL)-1β in the hippocampus after CA/CPR, which was unchanged after 4-PCO treatment, while expression of antiinflammatory IL-10 increased significantly. We conclude that sEH inhibition after CA/CPR can alter the transcription profile in activated microglia to selectively induce antiinflammatory and neuroprotective IL-10 and reduce subsequent neuronal death. Switching microglial gene expression toward a neuroprotective phenotype is a promising new therapeutic approach for ischemic brain injury.

元の言語英語
ページ(範囲)1574-1581
ページ数8
ジャーナルJournal of Cerebral Blood Flow and Metabolism
33
発行部数10
DOI
出版物ステータス出版済み - 10 1 2013

Fingerprint

Epoxide Hydrolases
Cardiopulmonary Resuscitation
Microglia
Heart Arrest
Phenotype
Interleukin-10
Anti-Inflammatory Agents
Therapeutics
Memory Disorders
Interleukin-1
Brain Injuries
Inhibition (Psychology)
Hippocampus
Ischemia
Tumor Necrosis Factor-alpha
Gene Expression
Wounds and Injuries
Brain
Enzymes
4-phenylchalcone oxide

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

これを引用

Inhibition of soluble epoxide hydrolase after cardiac arrest/ cardiopulmonary resuscitation induces a neuroprotective phenotype in activated microglia and improves neuronal survival. / Wang, Jianming; Fujiyoshi, Tetsuhiro; Kosaka, Yasuharu; Raybuck, Jonathan D.; Lattal, K. Matthew; Ikeda, Mizuko; Herson, Paco S.; Koerner, Ines P.

:: Journal of Cerebral Blood Flow and Metabolism, 巻 33, 番号 10, 01.10.2013, p. 1574-1581.

研究成果: ジャーナルへの寄稿記事

Wang, Jianming ; Fujiyoshi, Tetsuhiro ; Kosaka, Yasuharu ; Raybuck, Jonathan D. ; Lattal, K. Matthew ; Ikeda, Mizuko ; Herson, Paco S. ; Koerner, Ines P. / Inhibition of soluble epoxide hydrolase after cardiac arrest/ cardiopulmonary resuscitation induces a neuroprotective phenotype in activated microglia and improves neuronal survival. :: Journal of Cerebral Blood Flow and Metabolism. 2013 ; 巻 33, 番号 10. pp. 1574-1581.
@article{48e3a71d72254611b7f9784a080fe741,
title = "Inhibition of soluble epoxide hydrolase after cardiac arrest/ cardiopulmonary resuscitation induces a neuroprotective phenotype in activated microglia and improves neuronal survival",
abstract = "Cardiac arrest (CA) causes hippocampal neuronal death that frequently leads to severe loss of memory function in survivors. No specific treatment is available to reduce neuronal death and improve functional outcome. The brain's inflammatory response to ischemia can exacerbate injury and provides a potential treatment target. We hypothesized that microglia are activated by CA and contribute to neuronal loss. We used a mouse model to determine whether pharmacologic inhibition of the proinflammatory microglial enzyme soluble epoxide hydrolase (sEH) after CA alters microglial activation and neuronal death. The sEH inhibitor 4-phenylchalcone oxide (4-PCO) was administered after successful cardiopulmonary resuscitation (CPR). The 4-PCO treatment significantly reduced neuronal death and improved memory function after CA/CPR. We found early activation of microglia and increased expression of inflammatory tumor necrosis factor (TNF)- and interleukin (IL)-1β in the hippocampus after CA/CPR, which was unchanged after 4-PCO treatment, while expression of antiinflammatory IL-10 increased significantly. We conclude that sEH inhibition after CA/CPR can alter the transcription profile in activated microglia to selectively induce antiinflammatory and neuroprotective IL-10 and reduce subsequent neuronal death. Switching microglial gene expression toward a neuroprotective phenotype is a promising new therapeutic approach for ischemic brain injury.",
author = "Jianming Wang and Tetsuhiro Fujiyoshi and Yasuharu Kosaka and Raybuck, {Jonathan D.} and Lattal, {K. Matthew} and Mizuko Ikeda and Herson, {Paco S.} and Koerner, {Ines P.}",
year = "2013",
month = "10",
day = "1",
doi = "10.1038/jcbfm.2013.111",
language = "English",
volume = "33",
pages = "1574--1581",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - Inhibition of soluble epoxide hydrolase after cardiac arrest/ cardiopulmonary resuscitation induces a neuroprotective phenotype in activated microglia and improves neuronal survival

AU - Wang, Jianming

AU - Fujiyoshi, Tetsuhiro

AU - Kosaka, Yasuharu

AU - Raybuck, Jonathan D.

AU - Lattal, K. Matthew

AU - Ikeda, Mizuko

AU - Herson, Paco S.

AU - Koerner, Ines P.

PY - 2013/10/1

Y1 - 2013/10/1

N2 - Cardiac arrest (CA) causes hippocampal neuronal death that frequently leads to severe loss of memory function in survivors. No specific treatment is available to reduce neuronal death and improve functional outcome. The brain's inflammatory response to ischemia can exacerbate injury and provides a potential treatment target. We hypothesized that microglia are activated by CA and contribute to neuronal loss. We used a mouse model to determine whether pharmacologic inhibition of the proinflammatory microglial enzyme soluble epoxide hydrolase (sEH) after CA alters microglial activation and neuronal death. The sEH inhibitor 4-phenylchalcone oxide (4-PCO) was administered after successful cardiopulmonary resuscitation (CPR). The 4-PCO treatment significantly reduced neuronal death and improved memory function after CA/CPR. We found early activation of microglia and increased expression of inflammatory tumor necrosis factor (TNF)- and interleukin (IL)-1β in the hippocampus after CA/CPR, which was unchanged after 4-PCO treatment, while expression of antiinflammatory IL-10 increased significantly. We conclude that sEH inhibition after CA/CPR can alter the transcription profile in activated microglia to selectively induce antiinflammatory and neuroprotective IL-10 and reduce subsequent neuronal death. Switching microglial gene expression toward a neuroprotective phenotype is a promising new therapeutic approach for ischemic brain injury.

AB - Cardiac arrest (CA) causes hippocampal neuronal death that frequently leads to severe loss of memory function in survivors. No specific treatment is available to reduce neuronal death and improve functional outcome. The brain's inflammatory response to ischemia can exacerbate injury and provides a potential treatment target. We hypothesized that microglia are activated by CA and contribute to neuronal loss. We used a mouse model to determine whether pharmacologic inhibition of the proinflammatory microglial enzyme soluble epoxide hydrolase (sEH) after CA alters microglial activation and neuronal death. The sEH inhibitor 4-phenylchalcone oxide (4-PCO) was administered after successful cardiopulmonary resuscitation (CPR). The 4-PCO treatment significantly reduced neuronal death and improved memory function after CA/CPR. We found early activation of microglia and increased expression of inflammatory tumor necrosis factor (TNF)- and interleukin (IL)-1β in the hippocampus after CA/CPR, which was unchanged after 4-PCO treatment, while expression of antiinflammatory IL-10 increased significantly. We conclude that sEH inhibition after CA/CPR can alter the transcription profile in activated microglia to selectively induce antiinflammatory and neuroprotective IL-10 and reduce subsequent neuronal death. Switching microglial gene expression toward a neuroprotective phenotype is a promising new therapeutic approach for ischemic brain injury.

UR - http://www.scopus.com/inward/record.url?scp=84885021977&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84885021977&partnerID=8YFLogxK

U2 - 10.1038/jcbfm.2013.111

DO - 10.1038/jcbfm.2013.111

M3 - Article

VL - 33

SP - 1574

EP - 1581

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 10

ER -