Chronic Blood-Brain Barrier Damage Following a Traumatic Brain Injury: A Role for the Inflammasome?

Severe traumatic brain injury (TBI) is a leading cause of disability and death, yet there is no therapy aimed at improving outcomes. The blood-brain barrier (BBB) regulates the exchange between plasma components and brain parenchyma. Humans with TBI have BBB damage that is thought to drive dementia and neurodegeneration, and previous studies show BBB damage in mouse TBI models associated with angiogenesis. One potential cause is persistent cytokine signaling by interleukin-1b (IL-1b) since it has been shown to increase BBB permeability. IL-1b signaling functions downstream of the inflammasome platform, which only assembles in non-homeostatic conditions. The ripoptosome is a protein complex that may regulate inflammasome activation.  A core component of the ripoptosome is receptor-interacting protein kinase-1 (RIPK1), which contains a scaffolding domain necessary for pro-survival gene expression and a kinase domain implicated in programmed cell death (PCD). We used a controlled-cortical impact (CCI) of cerebral contusion in mice and looked for evidence of inflammasomes present in brain tissue following CCI. Here we also examine whether angiogenesis is altered in mice that are deficient in RIPK1 kinase activity following CCI. We hope these studies may point the way forward for reducing the likelihood of developing BBB-damage associated dementia in severe TBI patients.