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Although the concepts of secondary injury and neuroprotection after neurotrauma are experimentally well supported, clinical trials of neuroprotective agents in traumatic brain injury or spinal cord injury have been disappointing. Most strategies to date have used drugs directed toward a single pathophysiological mechanism that contributes to early necrotic cell death. Given these failures, recent research has increasingly focused on multifunctional (i.e., multipotential, pluripotential) agents that target multiple injury mechanisms, particularly those that occur later after the insult. Here we review two such approaches that show particular promise in experimental neurotrauma: cell cycle inhibitors and small cyclized peptides. Both show extended therapeutic windows for treatment and appear to share at least one important target.