In stroke (brain ischemia), the leading cause of functional disability and mortality worldwide, despite continuous efforts both at experimental and clinical level in getting the better understanding, the only approved pharmacological treatment has been restricted to tissue plasminogen activator (tPA). Its complex pathophysiology starts with energy pump failure which ends with neuronal cell death. Ischemic cascade involves excessive glutamate release followed by raised intracellular sodium and calcium influx along with free radicals’ generation, activation of inflammatory cytokines, NO synthases, lipases, endonucleases and other apoptotic pathways leading to cell edema and death. At pre-clinical stage, several agents have tried and proven as an effective neuroprotectant in animal models of ischemia. However, these agents failed to show convincing results in terms of efficacy and safety when the trials were conducted in humans following stroke. This article highlights the various agents which have tried in the past but failed to translate into stroke therapy along with key points that are responsible for lagging of experimental success to translational failure in stroke treatment.
Keywords: Stroke, ischemia, neuroprotection, pathophysiology, pharmacotherapy, pre-clinical studies, clinical trials, STAIR criteria.
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