Description:
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<jats:p>In stroke (cerebral ischemia), despite continuous efforts both at the experimental and
clinical level, the only approved pharmacological treatment has been restricted to tissue plasminogen
activator (tPA). Stroke is the leading cause of functional disability and mortality throughout
worldwide. Its pathophysiology starts with energy pump failure, followed by complex signaling
cascade that ultimately ends in 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 the pre-clinical stage, several agents have been
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 been tried
in the past but failed to translate into stroke therapy along with key points that are responsible for
the lagging of experimental success to translational failure in stroke treatment.</jats:p>
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