Neurotoxicity and stroke

Abstract

Stroke is the clinical manifestation of the occlusion (ischemic stroke) or rupture of a blood vessel to the brain (hemorrhagic stroke). Neurotoxicity is triggered in stroke by the failure of oxygen delivery and the buildup of metabolites resulting in a cascade of harmful physiological events. Here, we review and contrast neurotoxicity and its corollary - neuroprotection - in the context of preclinical (animal) and clinical (patient) drug trials. Preclinical tests are distinguished by greater homogeneity, earlier time windows for treatment, and greater probability of success. Many of the same processes have been targeted in preclinical and clinical trials - such as excitotoxicity, oxidation, inflammation, and trophic factors - however, it is not a seamless flow from bench to bedside and back. Current trends in stroke neuroprotection include combination neuroprotection and improved trial designs. Areas where drug development in stroke could be improved include better target identification, development of lead drug candidates prior to preclinical testing and use of computational tool for prediction of toxicity based on biochemical pathway and drug characteristics.