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

发育性脑损伤中 caspase-1 依赖性白细胞介素和基质金属蛋白酶的局部和全身激活

• 批准号: 5407506
• 负责人: Professorin Dr. Hrissanthi Ikonomidou
• 金额: --
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2003
• 资助国家: 德国
• 起止时间: 2002-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5407506?language=en
• 关键词: Local; systemic; activation; caspase; dependent

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.

创伤性脑损伤是儿童发病的主要原因。我们建立了一种动物模型来研究发育中的大鼠脑外伤，并描述了外伤可触发两种类型的神经变性，即快速兴奋毒性和延迟凋亡。脑外伤后细胞死亡的程度与年龄有关，在年轻年龄组中最为严重。在发育中的大脑中，导致创伤性损伤后细胞死亡的机制尚不清楚。本项目旨在研究脑外伤后，caspase-1依赖性白介素（IL-1b、IL-18）和基质金属蛋白酶（MMP-2和9）在幼龄大鼠和敲除小鼠大脑和外周器官中的激活情况。利用神经病理学和分子技术，我们将研究caspase-1依赖性白介素和基质金属蛋白酶2和9的激活是否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与创伤性脑损伤的严重程度有关。此外，我们想要确定这些由脑外伤诱导的白细胞介素和细胞外蛋白酶是否会根据创伤的严重程度在周围器官中变得活跃。