Protection from brain damage and bacterial infection in murine stroke by the novel caspase-inhibitor Q-VD-OPH

Abstract

Infarction size and infections are important determinants of stroke outcome in humans. Bacterial infections are promoted by stroke-induced immunodeficiency which in experimental stroke is mainly characterized by extensive lymphocyte apoptosis and dysfunction. Pharmacological inhibition of caspases may improve stroke outcome not only by reducing apoptotic brain damage but also by attenuating stroke-induced immunodeficiency. We investigated the effects of systemic administration of the novel, non-toxic caspase-inhibitor quinolyl-valyl-O-methylaspartyl-[-2,6-difluorophenoxy]-methyl ketone (Q-VD-OPH) on stroke-induced neuronal and lymphocyte apoptosis, susceptibility to infections, and mortality in a murine model of stroke induced by middle cerebral artery occlusion (MCAO). Q-VD-OPH reduced ischemic brain damage and stroke-induced programmed cell death in thymus and spleen, decreased susceptibility to post-stroke bacteremia, and improved survival. Therefore, Q-VD-OPH may be a promising therapeutic agent in stroke.