Citation

de la Tremblaye PB, Bondi CO, Lajud N, Cheng JP, Radabaugh H, Kline AE. J. Neurotrauma 2016; 34(8): 1610-1622.

Affiliation

University of Pittsburgh, Physical Medicine & Rehabilitation , 3471 Fifth Avenue , Suite 201 , Pittsburgh, Pennsylvania, United States , 15213 ; klineae@upmc.edu.

Copyright

(Copyright © 2016, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2016.4790

PMID

27806662

Abstract

Environmental enrichment (EE) enhances cognition after traumatic brain injury (TBI). Galantamine (GAL) is an acetylcholinesterase inhibitor that may also promote benefits. Hence, the aims of this study were to assess the efficacy of GAL alone (standard (STD) housing) and in combination with EE in adult male rats after TBI. The hypothesis was that both therapies would confer motor, cognitive, and histological benefits when provided singly, but their combination would be more efficacious. Anesthetized rats received a controlled cortical impact or sham injury and then were randomly assigned to receive GAL (1, 2, or 3 mg/kg; i.p.) or saline vehicle (1 mL/kg; i.p.) beginning 24 hours after surgery and once daily for 21 days [experiment 1]. Motor (beam-balance/walk) and cognitive (Morris water maze; MWM) assessments were conducted on post-operative days 1-5 and 14-19, respectively. Cortical lesions volumes were quantified on day 21. Sham controls were better vs. all TBI groups. No differences in motor function or lesion volumes were observed among the TBI groups [p > 0.05]. In contrast, GAL (2 mg/kg) enhanced MWM performance vs. VEH and GAL (1 and 3 mg/kg) [p < 0.05]. In experiment 2, GAL (2 mg/kg) or VEH was combined with EE and the data were compared to the STD-housed groups from experiment 1. EE alone enhanced motor performance over the VEH and GAL (2 mg/kg)-treated STD-housed groups [p < 0.05]. Moreover, both EE groups (VEH or GAL) facilitated spatial learning and reduced lesion size vs. STD + VEH controls [p < 0.05]. No additional benefits were observed with the combination paradigm, which does not support the hypothesis. Overall, the data demonstrate that EE and once daily GAL (2 mg/kg) promote cognitive recovery after TBI. Importantly, the combined therapies did not negatively affect outcome and thus this therapeutic protocol may have clinical utility.

Language: en