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Journal Article


Cannella LA, McGary H, Ramirez SH. Exp. Neurol. 2019; 317: 191-201.


Department of Pathology and Laboratory Medicine, The Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Center for Substance Abuse Research, The Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA; Shriners Hospitals Pediatric Research Center, The Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA. Electronic address:


(Copyright © 2019, Elsevier Publishing)






Recent reports provide evidence for increased risk of substance use disorders (SUD) among patients with a history of early-life traumatic brain injury (TBI). Preclinical research utilizing animal models of TBI have identified injury-induced inflammation, blood-brain barrier permeability, and changes to synapses and neuronal networks within regions of the brain associated with the perception of reward. Importantly, these reward pathway networks are underdeveloped during childhood and adolescence, and early-life TBI pathology may interrupt ongoing maturation. As such, maladaptive changes induced by juvenile brain injury may underlie increased susceptibility to SUD. In this review, we describe the available clinical and preclinical evidence that identifies SUD as a persistent psychiatric consequence of pediatric neurotrauma by discussing (1) the incidence of early-life TBI, (2) how preclinical studies model TBI and SUD, (3) TBI-induced neuropathology and neuroinflammation in the corticostriatal regions of the brain, and (4) the link between childhood or adolescent TBI and addiction in adulthood. In summary, preclinical research utilizes an innovative combination of models of early-life TBI and SUD to recapitulate clinical features and to determine how TBI promotes a risk for the development of SUD. However, causal processes that link TBI and SUD remain unclear. Additional research to identify and therapeutically target underlying mechanisms of aberrant reward pathway development will provide a launching point for TBI and SUD treatment strategies.

Copyright © 2019. Published by Elsevier Inc.

Language: en


Addiction; Animal models of addiction; Early-life traumatic brain injury; Neuroinflammation; Substance use disorders


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