Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (UMR5287)

Aquitaine Institute for Cognitive and Integrative Neuroscience



INCIA - UMR 5287- CNRS
Université de Bordeaux

Zone nord Bat 2 2ème étage
146, rue Léo Saignat
33076 Bordeaux cedex
France

Téléphone 05.57.57.15.51
Télécopie 05.56.90.14.21

Supervisory authorities

CNRS Ecole Pratique des Hautes Etudes Université de Bordeaux

Our partners

Neurocampus Unitéde Formation de Biologie

GDR

GDR Robotique GDR Mémoire GDR Multi-électrodes

Search




Home > Latest publications

Rodriguez-Grande B, Ichkova A, Lemarchant S, Badaut J. AAPS J. 2017 Sep 13. doi: 10.1208/s12248-017-0123-3.

by Loïc Grattier - published on

Early to Long-Term Alterations of CNS Barriers After Traumatic Brain Injury: Considerations for Drug Development.

https://www.ncbi.nlm.nih.gov/pubmed/28905273

Abstract
Traumatic brain injury (TBI) is one of the leading causes of death and disability, particularly amongst the young and the elderly. The functions of the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) are strongly impaired after TBI, thus affecting brain homeostasis. Following the primary mechanical injury that characterizes TBI, a secondary injury develops over time, including events such as edema formation, oxidative stress, neuroinflammation, and alterations in paracelullar and transcellular transport. To date, most therapeutic interventions for TBI have aimed at direct neuroprotection during the acute phase and have not been successful. Targeting the barriers of the central nervous system (CNS) could be a wider therapeutic approach, given that restoration of brain homeostasis would benefit all brain cells, including neurons. Importantly, BBB disregulation has been observed even years after TBI, concomitantly with neurological and psychosocial sequelae; however, treatments targeting the post-acute phase are scarce. Here, we review the mechanisms of primary and secondary injury of CNS barriers, the accumulating evidence showing long-term damage to these structures and some of the therapies that have targeted these mechanisms. Finally, we discuss how the injury characteristics (hemorrhagic vs non-hemorrhagic, involvement of head rotation, gray vs white matter), the sex, and the age of the patient need to be carefully considered to improve clinical trial design and outcome interpretation, and to improve future drug development.
KEYWORDS:
blood-brain barrier; blood-cerebrospinal-fluid barrier; drug targets; gliovascular unit; traumatic brain injury