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

创伤性脑损伤是儿科人群发病的主要原因。我们已经开发了一种动物模型来研究发育中的大鼠脑中的创伤性损伤，并描述了两种类型的神经变性可以由创伤触发，快速兴奋毒性和延迟凋亡。脑创伤后细胞死亡的程度与年龄有关，在年轻年龄组中最严重。在发育中的大脑中导致创伤性损伤后细胞死亡的机制知之甚少。本项目旨在表征脑创伤后新生大鼠和基因敲除小鼠脑和外周器官中caspase-1依赖性白细胞介素（IL-1b，IL-18）和基质金属蛋白酶（MMP-2和9）的活化。使用神经病理学和分子技术，我们将检查是否激活caspase-1依赖性白细胞介素和基质金属蛋白酶2和9发生在创伤性脑组织中，表征产生它们的细胞类型，并确定它们的激活是否有助于创伤性脑损伤的严重程度。此外，我们想确定是否这些相同的白细胞介素和细胞外蛋白酶，诱导脑内的脑创伤可能会成为活跃的外周器官，这取决于创伤的严重程度。

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.