Figure 4.

Potential mechanisms relating blast-induced vascular injury to neuroinflammation and neurobehavioral dysfunction. Mechanical injury to blood vessels induces local production of inflammatory mediators including cytokines, chemokines, and cell adhesion molecules through largely cell-mediated mechanisms. Mechanical injury also induces oxidative stress which can be associated with induction of an inflammatory response. Changes in BBB permeability could support initiation of an inflammatory reaction acutely and help sustain a response chronically. Blast-induced damage to the choroid plexus may alter blood-CSF barrier function which has been linked to induction of an inflammatory response. Impaired BBB function and bidirectional signaling between CNS and systemic inflammatory responses could amplify both reactions. Chronic immune activation could lead to neurobehavioral changes in the absence of direct neuronal pathology. Vascular pathology could also disrupt recently described glymphatic pathways that move CSF through the brain parenchyma.