INTRAVENTRICULAR HEMORRHAGE AND CEREBROVASCULAR REACTIVITY

脑室内出血仍然是一个常见的事件， 新生儿，永久性神经功能缺损的发生率很高， 幸存者 虽然许多以前的研究试图确定其 病因学，相对较少的是已知的功能状态， 暴露于血管外血液后的脑血管。 对成人的广泛临床和实验研究表明， 脑血管痉挛及相关脑血管反应性损害 是由蛛网膜下腔的血液引起的， 功能障碍又导致继发性缺血性损伤。 此外，本发明还提供了一种方法， 似乎血管内皮细胞损伤继发于 血管外血液暴露可能是这种功能障碍的主要原因， 强调了内皮衍生的血管活性产物的重要性 如一氧化氮在控制脑血流中的作用。 我们假设：（1）新生儿脑动脉发生血管痉挛 （2）长时间暴露于血管外血液后， 损伤导致由血管痉挛脉管系统服务的脑区域， 以及（3）血液诱导的一氧化氮机制损伤 导致脑血管功能障碍， 新生儿脑损伤 大多数患有脑室内出血的婴儿， 进入侧脑室扩散到整个脑室系统 在后颅窝中聚集;因此， 这些婴儿通常会接触血液 因此，我们将使用 新生猪的斜坡窗，以提供实验通道， 后循环，这样我们就可以确定 脑池内注射的血液对这些血管的反应性的影响。 将通过以下方式记录基底动脉的血液诱导血管痉挛： 动脉横截面的形态计量学分析，以及 组织化学分析后颅窝结构， 组织学上 血管对生理和药理学的反应性 通过一氧化氮诱导血管舒张刺激将通过 荧光素视频显微镜和氢清除。 这些研究将 第一个在新生儿模型中系统地检查脑血管 继发于脑室内出血的反应性。

Intraventricular hemorrhage continues to be a common occurrence in the neonate, with a high incidence of permanent neurologic deficits in the survivors. Although many previous studies have attempted to identify its etiology, relatively little is known regarding the functional status of the cerebral vasculature following its exposure to extravascular blood. Extensive clinical and experimental studies in the adult indicate that cerebral vasospasm and related impairments in cerebrovascular reactivity result from blood in the subarachnoid space, and this vascular dysfunction, in turn, leads to secondary ischemic injury. In addition, it appears that vascular endothelial cell injury secondary to extravascular blood exposure may be a primary cause of such dysfunction, underscoring the importance of endothelium-derived vasoactive products such as nitric oxide in the control of cerebral blood flow. We hypothesize that (1) vasospasm occurs in neonate cerebral arteries following prolonged exposure to extravascular blood; (2) that ischemic injury results in brain regions served by the vasospastic vasculature, and (3) that blood-induced impairments in nitric oxide-based mechanisms of vascular regulation contribute to cerebrovascular dysfunction and brain injury in the neonate. In the majority of infants suffering intraventricular hemorrhage, blood entering the lateral ventricles spreads throughout the ventricular system and collects in the posterior fossa; thus, the posterior circulation of these babies is typically exposed to blood. We will therefore use a clival window in newborn pigs to provide experimental access to the posterior circulation so that we can determine the delayed effects of intracisternally injected blood on the reactivity of these vessels. Blood-induced vasospasm of the basilar artery will be documented by morphometric analyses of arterial cross sections, and ischemic injury of the posterior fossa structures will be analyzed histochemically and histologically. Vascular reactivity to physiologic and pharmacologic stimuli that induce vasodilation via nitric oxide will be quantified by fluorescein videomicroscopy and hydrogen clearance. These studies will be the first in a neonate model to systematically examine cerebrovascular reactivity secondary to intraventricular hemorrhage.