From spreading depolarization to blood-brain barrier dysfunction: navigating traumatic brain injury for novel diagnosis and therapy.

Abstract

Considerable strides in medical interventions during the acute phase of traumatic brain injury (TBI) have brought improved overall survival rates. However, following TBI, people often face ongoing, persistent and debilitating long-term complications. Here, we review therecent literature to propose possiblemechanisms that lead from TBI to long-term complications, focusing particularly on the involvement of a compromised blood-brain barrier (BBB). We discuss evidence for the role of spreading depolarization as a key pathological mechanism associated with microvascular dysfunction and thetransformation of astrocytes to an inflammatory phenotype. Finally, we summarize new predictive and diagnostic biomarkers and explore potential therapeutic targets for treatinglong-term complications of TBI.