Investigating cerebrovascular dysfunction and cerebral atrophy in severe traumatic brain injury

项目总结 脑萎缩常见于穿透性重型创伤性脑损伤(STBI)幸存者。脑渗透 血液中的细胞毒蛋白和免疫细胞是脑血管功能障碍的一个重要因素 与进行性脑萎缩和阿尔茨海默病痴呆的发病有关。然而，目前还没有 努力开发可预防脑血管功能障碍和外周渗入的介入疗法 在穿透性脑损伤中，免疫细胞进入大脑。我们的中心假设是急性植入的工程化软骨素 硫酸盐(ECS)3D基质将加速脑血管修复，防止脑萎缩和功能丧失 老鼠。我们建议使用一种新的穿透sTBI的临床前大鼠模型来验证我们的假设，在以下两个特定的 目标：AIM-1。脑外伤后脑血管通透性和免疫细胞组成的特征。AIM-2。确定 ECS基质植入物在脑血管修复和功能恢复中的作用建议进行的研究包括 有望为脑血管功能障碍在进行性神经变性和脑组织中的作用提供新的见解 颅脑损伤后的萎缩。总而言之，这些研究将为组织工程脑植入物的开发提供信息，这些组织工程脑植入物可以 促进脑血管修复，预防脑损伤患者脑容量丢失和功能障碍。

PROJECT SUMMARY Cerebral atrophy is commonly encountered in penetrating severe Traumatic Brain Injury (sTBI) survivors. Brain infiltration of blood-borne cytotoxic proteins and immune cells due to cerebrovascular dysfunction is an important factor contributing to progressive cerebral atrophy and onset of Alzheimer’s Disease dementia in sTBI patients. However, there have been no efforts to develop interventional therapies that can prevent cerebrovascular dysfunction and infiltration of peripheral immune cells into the brain in penetrating sTBI. Our central hypothesis is that acutely implanted engineered Chondroitin Sulfate (eCS) 3D matrices will accelerate cerebrovascular repair and prevent cerebral atrophy and loss of function in sTBI rats. We propose to test our hypothesis using a novel preclinical rat model of penetrating sTBI in the following two specific aims: Aim-1. Characterize cerebrovascular permeability and immune cell composition in sTBI. Aim-2. Determine the effectiveness of eCS matrix implants in mediating cerebrovascular repair and functional recovery. The proposed studies are expected to provide novel insight into the role of cerebrovascular dysfunction in progressive neurodegeneration and cerebral atrophy in sTBI. Collectively, these studies will inform the development of tissue engineered brain implants that can accelerate cerebrovascular repair and prevent brain volume loss and functional deficits in sTBI patients.