The neuroprotective effects of NMDAR antagonist, ifenprodil and ASIC1a inhibitor, flurbiprofen on post-ischemic cerebral injury ☆

Owing to the complex and multifactorial pathology of cerebral stroke, multiple drug therapy had long been advocated by STAIR committee for stroke successful treatment. In this context, we analyzed the effect of Ifenprodil, an NR2b selective NMDAR antagonist and its combination at lower doses with flurbiprofen, a selective ASIC1a inhibitor on rat model of focal cerebral ischemia. We found that the combination produced significant neuroprotective effect as produced by ifenprodil at higher doses, which was evidenced by reduction in infarct volume, neurological deficit and MDA levels. Further, histopathological studies revealed that, the combination not only attenuated the cell damage in striatal regions of ischemic brain, but also significantly inhibited apoptotic cell death, which was more pronounced than monotherapy with ifenprodil or flurbiprofen. Thus, it appears that the combination therapy will be more efficacious in offering neuroprotection on one hand and also lower the risks associated by mono-therapy with ifenprodil at higher doses.