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 5min 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.