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学術誌査読

22 被引用数 (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.

本文言語英語
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
10
DOI
出版ステータス出版済み - 10月 2013
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 神経学
  • 臨床神経学
  • 循環器および心血管医学

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