Background Environmental enrichment (EE) is a complex living milieu that has been shown to enhance functional recovery vs. standard (STD) housing after experimental traumatic brain injury (TBI) and therefore may be considered a rodent correlate of rehabilitation. However, the typical EE paradigm consists of continuous exposure to enrichment after TBI, which is inconsistent with the limited time frame in clinical rehabilitation. Objective To determine whether abbreviated EE (i.e., rehabilitation-relevant dose response) confers benefits similar to typical EE after TBI. Methods Adult male rats received either a controlled cortical impact (2.8 mm depth at 4 m/sec) or sham injury and were then randomly assigned to TBI + EE, TBI + EE (2hr), TBI + EE (4hr), TBI + EE (6hr), TBI + STD, and respective sham controls. Motor (beam-balance/beam-walk; BB/BW) and cognitive (Morris water maze; MWM) performance was assessed on post-operative days 1-5 and 14-19, respectively. Results The TBI + EE (2hr) and TBI + EE (4hr) groups were not statistically different from the TBI + STD group in any behavioral assessment. In contrast, the TBI + EE (6hr) group exhibited significant enhancement of motor and cognitive performance vs. the TBI + STD group, as well as the TBI + EE (2hr) and TBI + EE (4hr) groups (p < 0.003), and did not differ from the TBI + EE (typical) group. Conclusions These data demonstrate that abbreviated EE (6hr) produces motor and cognitive benefits similar to continuous EE after TBI and thus may be considered a dose-relevant rehabilitation paradigm.

Background Environmental enrichment (EE) confers benefits after traumatic brain injury (TBI) when provided daily for 6-hrs or greater, but not 2-hr or 4-hr, which more accurately reflects the daily amount of clinical rehabilitation. The lack of benefit with sub-therapeutic EE suggests that augmentation with galantamine (GAL), which enhances cognition after TBI, may be indicated to confer benefits. Objective To test the hypothesis that 2-hr and 4-hr of EE paired with GAL will provide benefits comparable to 24-hr EE alone. Moreover, all EE groups will perform better than the standard (STD)-housed GAL group. Methods Anesthetized rats received a TBI or sham injury and then were randomized to receive intraperitoneal injections of GAL (2 mg/kg) or saline vehicle (VEH; 1 mL/kg) beginning 24-hr after surgery and once daily while receiving EE for 2-hr, 4-hr, or 24-hr. Motor and cognitive assessments were conducted on post-operative days 1–5 and 14–19, respectively. Results Motor function was significantly improved in the TBI+24-hr EE group vs. the TBI+STD+VEH and TBI+STD+GAL groups [p<0.05]. Cognitive performance was enhanced in all EE groups, as well as in the TBI+STD+GAL vs. TBI+STD+VEH [p<0.05]. Moreover, the 2-hr EE and 4-hr EE groups receiving GAL did not differ from the 24-hr EE group [p>0.05] and performed better than GAL alone [p<0.05]. Conclusions The findings support the hypothesis and have clinical relevance as often only brief rehabilitation may be available in the clinic and thus augmenting with a pharmacotherapy like GAL may lead to outcomes that are significantly better than either therapy alone.