Therapeutic effects of modafinil in ischemic stroke; possible role of NF-κB downregulation.

The phenomenon of ischemic stroke receives maximal attention nowadays. Many studies are designed to discover new therapies for reducing debilitating consequences of this disorder. Development of stroke-related tissue damage is due to the combination of blood flow occlusion and reperfusion phase. Inflammatory pathways participate in excess oxidative stress formation after reperfusion. Modafinil is a well-known medication prescribed for sleep disorders. Recently, several studies have focused on finding new indications for modafinil treatment. Anti-inflammatory effects of modafinil through disrupting NF-κB signaling pathway is reported previously. Downregulation of inflammatory cytokines and further oxidative damage have also been mentioned in various experiments. So far, no specific experiment had been conducted to assess the anti-inflammatory effects of modafinil on ischemic stroke. We evaluated outcomes of acutely administered modafinil on post-stroke behaviors and histopathological features (including apoptotic caspase-3 expressing neurons) through bilateral common carotid artery occlusion in rats. Alterations in concentrations of TNFɑ and IL-1β were assessed, together with malon di-aldehyde (MDA) to represent oxidation level. Western blotting was used to reveal the involvement of NF-κB downregulation. Considering possible alterations in blood flow and neuronal metabolism, we also assessed the effects of modafinil on cerebral glucose metabolism through PET scan. Modafinil exhibited promising effects on remission of behavioral deficits and the number of degenerated neurons in ischemic hippocampus CA1 region. IL-1β and MDA levels were downregulated in treated animals. However, no significant alteration was observed in PET results and TNFɑ between treated and non-treated ischemic brains. Decreased protein levels of NF-κB was also measured in modafinil treated animals. Our findings demonstrate a promising therapeutic effect of modafinil for animal models of stroke.