Traumatic brain injury (TBI) is the leading cause of death in young adults and children. The treatment of TBI in the acute phase has improved substantially; however, the prevention and management of long-term complications remain a challenge. Blood-brain barrier (BBB) breakdown has often been documented in patients with TBI, but the role of such vascular pathology in neurological dysfunction has only recently been explored. Animal studies have demonstrated that BBB breakdown is involved in the initiation of transcriptional changes in the neurovascular network that ultimately lead to delayed neuronal dysfunction and degeneration. Brain imaging data have confirmed the high incidence of BBB breakdown in patients with TBI and suggest that such pathology could be used as a biomarker in the clinic and in drug trials. Here, we review the neurological consequences of TBI, focusing on the long-term complications of such injuries. We present the clinical evidence for involvement of BBB breakdown in TBI and examine the primary and secondary mechanisms that underlie such pathology. We go on to consider the consequences of BBB injury, before analyzing potential mechanisms linking vascular pathology to neuronal dysfunction and degeneration, and exploring possible targets for treatment. Finally, we highlight areas for future basic research and clinical studies into TBI.

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Blood–brain barrier breakdown as a therapeutic target in traumatic brain injury

Changes in the demographics, approach, and treatment of traumatic brain injury (TBI) patients require regular evaluation of epidemiological profiles, injury severity classification, and outcomes. This prospective multicenter study provides detailed information on TBI-related variables of 508 moderate-to-severe TBI patients. Variability in epidemiology and outcome is examined by comparing our cohort with previous multicenter studies. Additionally, the relation between outcome and injury severity classification assessed at different time points is studied. Based on the emergency department Glasgow Coma Scale (GCS), 339 patients were classified as having severe and 129 as having moderate TBI. In 15%, the diagnosis differed when the accident scene GCS was used for classification. In-hospital mortality was higher if severe TBI was diagnosed at both time points (44%) compared to moderate TBI at one or both time points (7–15%, p<0.001). Furthermore, 14% changed diagnosis when a threshold (≥6 h) for impa...

Epidemiology, Severity Classification, and Outcome of Moderate and Severe Traumatic Brain Injury: A Prospective Multicenter Study

Severe Traumatic Brain Injury in Infants, Children, and Adolescents in 2019: Some Overdue Progress, Many Remaining Questions, and Exciting Ongoing Work in the Field of Traumatic Brain Injury ResearchIn this Supplement to Pediatric Critical Care Medicine, we are pleased to present the Third Edition o

Guidelines for the Management of Pediatric Severe Traumatic Brain Injury, Third Edition: Update of the Brain Trauma Foundation Guidelines.

Background
The role of acute coagulopathy after traumatic brain injury (TBI) on outcome has gained increasing appreciation over the recent years. This study was conducted to assess the frequency, outcome, and risk factors associated with this complication.

Charles L. Schelein

Papers

Guidelines for prehospital management of traumatic brain injury 2nd edition.