Modulation of NADPH oxidase activation in cerebral ischemia/reperfusion injury in rats

Tiziana Genovese, Emanuela Mazzon, Irene Paterniti, Emanuela Esposito, Placido Bramanti, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

Abstract

NADPH oxidase is a major complex that produces reactive oxygen species (ROSs) during the ischemic period and aggravates brain damage and cell death after ischemic injury. Although many approaches have been tested for preventing production of ROSs by NADPH oxidase in ischemic brain injury, the regulatory mechanisms of NADPH oxidase activity after cerebral ischemia are still unclear. The aim of this study is identifying apocynin as a critical modulator of NADPH oxidase and elucidating its role as a neuroprotectant in an experimental model of brain ischemia in rat. Treatment of apocynin 5 min before of reperfusion attenuated cerebral ischemia in rats. Administration of apocynin showed marked reduction in infarct size compared with that of control rats. Medial carotid artery occlusion (MCAo)-induced cerebral ischemia was also associated with an increase in, nitrotyrosine formation, as well as IL-1β expression, IκB degradation and ICAM expression in ischemic regions. These expressions were markedly inhibited by the treatment of apocynin. We also demonstrated that apocynin reduces levels of apoptosis (TUNEL, Bax and Bcl-2 expression) resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. This new understanding of apocynin induced adaptation to ischemic stress and inflammation could suggest novel avenues for clinical intervention during ischemic and inflammatory diseases.

Original languageEnglish
Pages (from-to)92-102
Number of pages11
JournalBrain Research
Volume1372
DOIs
Publication statusPublished - Feb 4 2011

Keywords

  • Apoptosis
  • Cerebral ischemia-reperfusion
  • Nitrosative stress
  • Proinflammatory cytokines

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

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