Citation

Margulies SS, Anderson GD, Atif F, Badaut J, Clark RSB, Empey P, Guseva M, Hoane MR, Huh JW, Pauly JR, Raghupathi R, Scheff S, Stein D, Tang H, Hicks M. J. Neurotrauma 2015; 33(1): 101-112.

Affiliation

University of Pennsylvania, Bioengineering , 3320 smith walk , Philadelphia, Pennsylvania, United States , 19104-6392 ; margulie@seas.upenn.edu.

Copyright

(Copyright © 2015, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2014.3855

PMID

25970337

Abstract

Patients enrolled in clinical trials for traumatic brain injury (TBI) may present with heterogeneous features over a range of injury severity, such as diffuse axonal injury, ischemia, edema, hemorrhage, oxidative damage, mitochondrial and metabolic dysfunction, excitotoxicity, inflammation and other pathophysiological processes. To determine if combination therapies might be more effective than a monotherapy at attenuating moderate TBI or promoting recovery, the National Institutes of Health funded six preclinical studies in adult and immature male rats to evaluate promising acute treatments alone and in combination. Each of the studies had a solid rationale for their approach based on previous research, but only one reported significant improvements in long-term outcomes across a battery of behavioral tests. Four studies had equivocal results because of a lack of sensitivity of the outcome assessments. One study demonstrated worse results with the combination in comparison to monotherapies. While specific research findings are reported elsewhere, this paper provides an overview of their study designs, insights and recommendations for future research aimed at therapy development for TBI.

Language: en