Targeting Oxidative Stress Injury after Ischemic Stroke in Conscious Rats : Limited Benefits with Apocynin Highlight the Need to Incorporate Long Term Recovery

Abstract EN

NADPH oxidase is a major source of superoxide anion following stroke and reperfusion.

This study evaluated the effects of apocynin, a known antioxidant and inhibitor of Nox2 NADPH, on neuronal injury and cell-specific responses to stroke induced in the conscious rat.

Apocynin treatment (50 mg/kg i.p.) commencing 1 hour prior to stroke and 24 and 48 hours after stroke significantly reduced infarct volume in the cortex by ~ 60%, but had no effect on striatal damage or neurological deficits.

In situ detection of reactive oxygen species (ROS) using dihydroethidium fluorescence revealed that increased ROS detected in OX-42 positive cells following ischemia was reduced in apocynin-treated rats by ~ 51%, but surprisingly increased in surrounding NeuN positive cells of the same rats by ~ 27%, in comparison to the contralateral hemisphere.

Reduced ROS from activated microglia/macrophages treated with apocynin was associated with reduced Nox2 immunoreactivity without change to the number of cells.

These findings confirm the protective effects of apocynin and indicate a novel mechanism via reduced Nox2 expression.

We also reveal compensatory changes in neuronal ROS generation as a result of Nox2 inhibition and highlight the need to assess long term individual cell responses to inhibitors of oxidative stress.