Impact of pharmacological treatments on outcome in adult rodents after traumatic brain injury: a meta-analysis

Abstract

Pharmacological treatments have been widely investigated in pre-clinical animal trials to evaluate their usefulness in reducing cognitive, behavioural and motor problems after traumatic brain injury (TBI). However, the relative efficacy of these agents has yet to be evaluated, making it difficult to assess the strength of evidence for their use in a clinical population. A meta-analytic review of research (1980–2009) was therefore conducted to examine the impact of pharmacological treatments administered to adult male rodents after experimental TBI on cognitive, behavioural, and motor outcome. The PubMed and PsycInfo databases were searched using 35 terms. Weighted Cohen’s d effect sizes, percent overlap, Fail-Safe N statistics and confidence intervals were calculated for each treatment. In total, 91 treatments were evaluated in 223 pre-clinical trials, comprising 5988 rodents. Treatments that were investigated by multiple studies and showed large and significant treatment effects were of greatest interest. Of the 16 treatments that were efficacious, six improved cognition, 10 improved motor function and no treatment improved behaviour (depression/anxiety, aggression, zoosocial behaviour). Treatment benefits were found across a range of TBI models. Drug dosage and treatment interval impacted on treatment effects.