THE ROLE OF ACTIVATED NEUTROPHILS IN SECONDARY BRAIN INJURY

中性粒细胞在组织损伤区域的激活和积聚 越来越被认为是有害的亲油的潜在来源之一 炎症活动可延长或以其他方式加剧原发 侮辱。这项研究旨在调查中性粒细胞对 21-氨基类固醇对大鼠血管源性和细胞毒性水肿的调节作用 创伤性脑损伤。该提案涉及两个急性动物模型 偏侧半球损伤；模拟血管生成的冷冻性损伤 水肿，和冲击性损伤，以模拟血管生成和 细胞毒性水肿。氯化物/重碳酸盐的差异效应 交换阻滞剂L644,711，它抑制中性粒细胞功能和 星形胶质细胞肿胀，抗中性粒细胞抗血清，耗尽中性粒细胞 系统和类脂抑制剂拉扎罗U78517F 过氧化，将在这两个模型中被确定为单独处理 范例。要监测、测量和对比的参数 确定这些治疗方法对颅内的不同影响 血压、脑血流量、组织梗塞、大脑半球体积和水 重量、细胞内和细胞外间隙的比率以及细胞间隙的程度 中性粒细胞渗入。这些研究的结果可能支持 中性粒细胞调节作为急性心肌梗死治疗的一种新策略 创伤性脑损伤。

The activation and accumulation of neutrophils in areas of tissue injury is being increasingly recognized as one potential source of deleterious pro- inflammatory activity which can extend or otherwise exacerbate the primary insult. This study is designed to investigate the impact of neutrophil modulation and a 21-aminosteroid on vasogenic and cytotoxic edema of traumatic brain injury. The proposal involves two acute animal models of lateralized hemispheric injury; a cryogenic lesion to model vasogenic edema, and a percussive lesion to model a combination of vasogenic and cytotoxic edema. The differential effects of the chloride/bicarbonate exchange blocker, L644,711, which inhibits neutrophil function and astrocyte swelling, anti-neutrophil antisera, which depletes neutrophils systematically and the lazaroid U78517F, an inhibitor of lipid peroxidation, will be determined in these two models as separate treatment paradigms. The parameters to be monitored, measured and contrasted to establish the differential impact of these treatments are intracranial pressure, cerebral blood flow, tissue infarct, hemispheric volume and water weight, the ratio of intracellular to extracellular space and the extent of neutrophil infiltration. The results of these studies may support neutrophil modulation as a novel strategy in the acute management of traumatic brain injury.