In this chapter, we have identified the major reasons for failure of neuroprotective agents to show benefit in clinical trials. The discussion has centered on issues of drug dosages, windows of opportunity, multiple mechanisms of injury and neuroprotection, combination therapy, gender differences, and clinical trial design and analysis. Despite the failure of clinical trials to show efficacy with pharmacologic neuroprotection over the years, optimism remains for the future. With newer clinical trial designs and protocols that are based on appropriate preclinical data and utilize the new strategies of stem cell technology, gene therapy, combination therapy, and gender-based differential responses, neuroprotective agents will surely be found in the future.

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