The blood-brain barrier (BBB) is formed by tightly connected cerebrovascular endothelial cells, but its normal function also depends on paracrine interactions between the brain endothelium and closely located glia. There is a growing consensus that brain injury, whether it is ischemic, hemorrhagic, or traumatic, leads to dysfunction of the BBB. Changes in BBB function observed after injury are thought to contribute to the loss of neural tissue and to affect the response to neuroprotective drugs. New discoveries suggest that considering the entire gliovascular unit, rather than the BBB alone, will expand our understanding of the cellular and molecular responses to traumatic brain injury (TBI). This review will address the BBB breakdown in TBI, the role of blood-borne factors in affecting the function of the gliovascular unit, changes in BBB permeability and post-traumatic edema formation, and the major pathophysiological factors associated with TBI that may contribute to post-traumatic dysfunction of the BBB. The key role of neuroinflammation and the possible effect of injury on transport mechanisms at the BBB will also be described. Finally, the potential role of the BBB as a target for therapeutic intervention through restoration of normal BBB function after injury and/or by harnessing the cerebrovascular endothelium to produce neurotrophic growth factors will be discussed.

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Traumatic brain injury (TBI) frequently results in neuroinflammation, which includes the invasion of neutrophils. After TBI, neutrophils infiltrate the choroid plexus (CP), a site of the blood-cerebrospinal fluid (CSF) barrier (BCSFB), and accumulate in the CSF space near the injury, from where these inflammatory cells may migrate to brain parenchyma. We have hypothesized that the CP functions as an entry point for neutrophils to invade the injured brain. Using the controlled cortical impact model of TBI in rats and an in vitro model of the BCSFB, we show that the CP produces CXC chemokines, such as cytokine-induced neutrophil chemoattractant (CINC)-1 or CXCL1, CINC-2a or CXCL3, and CINC-3 or CXCL2. These chemokines are secreted both apically and basolaterally from the choroidal epithelium, a prerequisite for neutrophil migration across epithelial barriers. Consistent with these findings, we also provide electron microscopic evidence that neutrophils infiltrate the choroidal stroma and subsequently reach the intercellular space between choroidal epithelial cells. This is the first detailed analysis of the BCSFB function related to neutrophil trafficking. Our observations support the role of this barrier in posttraumatic neutrophil invasion.