Environmental enrichment, alone or in combination with various pharmacotherapies, confers marked benefits after traumatic brain injury.

Traumatic brain injury (TBI) is a significant health care issue that affects over ten million people worldwide. Treatment options are limited with numerous failures resulting from single therapies. Fortunately, several preclinical studies have shown that combination treatment strategies may afford greater improvement and perhaps can lead to successful clinical translation, particularly if one of the therapies is neurorehabilitation. The aim of this review is to highlight TBI studies that combined environmental enrichment (EE), a preclinical model of neurorehabilitation, with pharmacotherapies. A series of PubMed search strategies yielded only nine papers that fit the criteria. The consensus is that EE provides robust neurobehavioral, cognitive, and histological improvement after experimental TBI and that the combination of EE with some pharmacotherapies can lead to benefits beyond those revealed by single therapies. However, it is noted that EE can be challenged by drugs such as the acetylcholinesterase inhibitor, donepezil, and the antipsychotic drug, haloperidol, which attenuate its efficacy. These findings may help shape clinical neurorehabilitation strategies to more effectively improve patient outcome. Potential mechanisms for the EE and pharmacotherapy-induced effects are also discussed. This article is part of the Special Issue entitled "Neurobiology of Environmental Enrichment".