Rehabilitative Success After Brain Trauma by Augmenting a Subtherapeutic Dose of Environmental Enrichment With Galantamine.

BACKGROUND: Environmental enrichment (EE) confers benefits after traumatic brain injury (TBI) when provided daily for > 6 hours, but not 2 or 4 hours, 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 and 4 hours of EE paired with GAL will provide benefits comparable to 24 hours of 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 hours after surgery and once daily while receiving EE for 2, 4, or 24 hours. Motor and cognitive assessments were conducted on postoperative days 1-5 and 14-19, respectively. RESULTS: Motor function was significantly improved in the TBI + 24-hour EE group versus the TBI + STD + VEH and TBI + STD + GAL groups ( P < .05). Cognitive performance was enhanced in all EE groups as well as in the TBI + STD + GAL versus TBI + STD + VEH ( P < .05). Moreover, the 2- and 4-hour EE groups receiving GAL did not differ from the 24-hour EE group ( P > .05) and performed better than GAL alone ( P < .05). CONCLUSIONS: The findings support the hypothesis and have clinical relevance because, often, only brief rehabilitation may be available in the clinic and, thus, augmenting with a pharmacotherapy such as GAL may lead to outcomes that are significantly better than either therapy alone.

Abbreviated environmental enrichment enhances neurobehavioral recovery comparably to continuous exposure after traumatic brain injury.

BACKGROUND: Environmental enrichment (EE) is a complex living milieu that has been shown to enhance functional recovery versus 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 (ie, 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/s) or sham injury and were then randomly assigned to TBI + EE, TBI + EE (2 hours), TBI + EE (4 hours), TBI + EE (6 hours), TBI + STD, and respective sham controls. Motor (beam balance/beam walk) and cognitive (Morris water maze) performance was assessed on postoperative days 1 to 5 and 14 to 19, respectively. RESULTS: The TBI + EE (2 hours) and TBI + EE (4 hours) groups were not statistically different from the TBI + STD group in any behavioral assessment. In contrast, the TBI + EE (6 hours) group exhibited significant enhancement of motor and cognitive performance when compared with the TBI + STD group, as well as the TBI + EE (2 hours) and TBI + EE (4 hours) groups (P < .003), and did not differ from the TBI + EE (typical) group. CONCLUSIONS: These data demonstrate that abbreviated EE (6 hours) produces motor and cognitive benefits similar to continuous EE after TBI and thus may be considered a dose-relevant rehabilitation paradigm.