The present study was designed to determine a dose-response relationship between
apocynin and
infarct volume as well as to provide a possible molecular mechanism mediating this effect. We tested the hypothesis that
apocynin protects against cell death following
stroke and
reperfusion injury.
Apocynin was administered 30 min prior to, or immediately following removal of
sutures used to occlude the middle cerebral artery (MCA) in male Sprague-Dawley rats. Following removal of the
sutures, the MCA was allowed to undergo 5.5h of reperfusion. Pretreatment with
apocynin 30 min prior to occlusion resulted in a dose-dependent reduction in
infarct volume by ∼50 %. Analysis of tissue from the ischemic cortex of
apocynin-treated rats showed an increase in the level of
glutathione (GSH),
protein adducts (HNE-His),
hydrogen peroxide (H(2)O(2)) and DNA fragmentation (apoptotic cell death) was also observed. This suggests that
apocynin may increase
antioxidant defense systems (GSH) to limit the degree of
ischemia-induced cellular stress. In addition, this moderate cell stress results in more apoptotic vs necrotic cell death, and thus may limit the spreading depression and total cell death that occurs following
ischemia/reperfusion. These effects may serve as a potential novel mechanism of action contributing to the
apocynin-induced neuroprotection observed.