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

• Published in: Neurorehabilitation and neural repair 2017-10, Vol.31 (10-11), p.977-985
• Main Authors: de la Tremblaye, Patricia B., Wellcome, Jody L., de Witt, Benjamin Wells, Cheng, Jeffrey P., Skidmore, Elizabeth R., Bondi, Corina O., Kline, Anthony E.
• Format: Article
• Language: English
• ISSN: 1545-9683; 1552-6844
• DOI: 10.1177/1545968317739999

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.