EPISODIC HYPOXIA AND ACUTE CEREBROVASCULAR INFLAMMATION

很大比例的新生儿会出现间歇性缺氧继发性 分娩并发症，早产儿呼吸暂停， 呼吸窘迫综合征 尽管一些人怀疑有脑损伤 例，间歇性缺氧可能导致脑损伤的潜在机制， 功能障碍和神经发育障碍，目前， 推测性的 因此，没有可用的预防性治疗。 为了开发合理的治疗方法来减少脑损伤， 间歇性缺氧，更好地了解这种压力对 新生儿大脑需要通过适当的临床前研究来实现， 模型 一般的假设是，间歇性缺氧刺激了 产生白细胞介素-1B、超氧自由基和腺苷，和 同时抑制一氧化氮的产生。 据推测 这些变化，单独或组合，激活内皮素，上调 粘附分子表达，并促进炎症反应， 危及微循环流动、血管反应性和血脑 屏障完整性 具体目标是：1）研究 细胞因子白细胞介素-1B介导白细胞内皮细胞粘附 其次是诱导E-选择素和细胞间粘附分子-1 （2）探讨超氧阴离子自由基在介导细胞间粘附分子（ICAM）中的作用 白细胞-内皮细胞粘附对间歇性缺氧的反应; 3） 研究一氧化氮（NO）如何影响白细胞-内皮细胞相互作用， 在间歇性缺氧的情况下其后果;和4）为了阐明 腺苷及其受体参与炎症反应， 间歇性缺氧

A significant percentage of newborns become intermittently hypoxic secondary to complications during labor and delivery, apnea of prematurity, and respiratory distress syndrome. Although brain injury is suspected in some cases, the potential mechanisms by which episodic hypoxia might cause cerebral dysfunction and neurodevelopmental handicaps are, at present, purely speculative. Thus, no prophylactic treatments are available. In order to develop rational therapeutics to reduce brain injury from intermittent hypoxia, a better understanding of the effects of this stress on the newborn brain needs to be realized by studies in appropriate preclinical models. The general hypothesis is that intermittent hypoxia stimulates the production of interleukin-1B, superoxide radical, and adenosine, and concomitantly inhibits the production of nitric oxide. It is hypothesized that these changes, singly and in combination, activate edothelium, upregulate adhesion molecule expression, and promote an inflammatory response that jeopardizes microcirculatory flow, vascular reactivity, and blood-brain barrier integrity. The specific aims are: 1) To examine the role of the cytokine interleukin-1B (IL-1B) in mediating leukocyte endothelial adherence secondary to its induction of E-selectin and intercellular adhesion molecule-1 (ICAM); 2) To investigate the participation of superoxide radical in mediating leukocyte-endothelial adherence in response to intermittent hypoxia; 3) To examine how nitric oxide (NO) affects leukocyte-endothelial interactions and their consequences in the setting of intermittent hypoxia; and 4) To elucidate the involvement of adenosine and its receptors in the inflammatory response to intermittent hypoxia.