Local and systemic activation of caspase-1 dependent interleukins and matrix-metalloproteinases in developmental brain trauma

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Traumatic brain injury is a major cause of morbidity in the pediatric population. We have developed an animal model to study traumatic injury in the developing rat brain and described that two types of neurodegeneration can be triggered by trauma, rapid excitotoxic and delayed apoptotic. The magnitude of cell death following brain trauma is age dependent and most profound in the young age groups. The mechanisms that lead to cell death following traumatic injury in the developing brain are poorly understood. This project aims to characterize activation of caspase-1 dependent interleukins (IL-1b, IL-18) and matrix-metalloproteinases (MMP-2 and 9) in the brain and in peripheral organs of infant rats and knockout mice following brain trauma. Using neuropathological and molecular techniques, we will examine whether activation of caspase-1 dependent interleukins and matrix metalloproteinases 2 and 9 occurs in traumatized brain tissue, characterize the cell types that produce them and determine whether their activation contributes to the severity of traumatic brain injury. Furthermore, we want to determine whether these same interleukins and extracellular proteases that are induced by brain trauma within the brain may become active in peripheral organs depending on trauma severity.