Aaps J
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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. ⋯ 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.