REGULATION OF CEREBRAL BLOOD FLOW IN THE FETUS

胎头扩张宫颈时对其施加的力 在正常分娩期间可以周期性地增加三倍于 羊水过多和可能导致一过性脑出血 缺血症。然而，胎头的病理生理后果 在实验动物模型中，压缩还没有得到很好的研究。 在近足月胎羊(130天)中，我们发现稳态升高 颅内压的变化导致了强大的升压反应 维持胎儿大脑血液流动和新陈代谢，但 反应不够迅速，不足以抵御周期性振荡 在国际比较方案中。初步数据表明，加压反应较小 在怀孕中期(90天)生效，对应于 髓鞘形成高峰期前皮质神经元回路的形成。在 目前的提案，我们将首先确定脑血管有多好 自动调节在适度升高的情况下维持脑血流 颅内压和升压反应在维持大脑功能方面的有效性 妊娠中期伴有严重的颅内压升高的代谢。我们会 将这些防御策略与近期可用的防御策略进行对比 胎羊。神经元产生的一氧化氮可能在 发育过程中突触的可塑性。脑血流量减少 出生后动物的一氧化氮合酶抑制表明 强效一氧化氮的产生有助于维持较高的血液水平 流。我们将确定一氧化氮的形成是否依赖于 妊娠90天到130天之间的机制是造成这种情况的部分原因 基础血流量增加三倍，低氧和低氧增强 自动调节反应。我们将描述周期性的影响 不同幅度和持续时间的头部按压对大脑皮质和大脑的影响 90d和130d纹状体血流、代谢和组织病理学 胎羊在子宫中。利用N-甲基-D-天冬氨酸拮抗剂 和QuisQualate受体，以及选择性免疫细胞化学标记 羊胎脑损伤后，我们将评价兴奋性毒素的作用 已知的损伤在出生后大鼠部分缺血和 缺氧。因此，这些研究将为 宫内和宫内脑血管调节的发育机制 建立一种新的可能发生的围产期脑损伤模型 在分娩期间，当体内平衡防御机制失效时。后果是什么？ 胎头受压可能对早产儿和 足月新生儿易受其他产前神经损伤 因素，从而导致脑性瘫痪和其他神经性疾病 残疾人士。

The forces exerted on the human fetal head as it dilates the cervix during normal labor can periodically increase three times that of amniotic fluid pressure and potentially result in transient cerebral ischemia. However, the pathophysiological consequences of fetal head compression has not been well studied in an experimental animal model. In near term fetal sheep (130 days), we found that steady state elevation of intracranial pressure (ICP) resulted in a powerful pressor response that maintained fetal cerebral blood flow and metabolism, but that the response was not sufficiently rapid to defend against cyclic oscillations in ICP. Preliminary data indicate that the pressor response is less effective at mid-gestation (90 days), corresponding to the period of cortical neuronal circuit formation prior to peak myelination. In the present proposal, we will first determine how well cerebrovascular autoregulation maintains cerebral blood flow with moderate elevation of ICP and how effective the pressor response is in maintaining cerebral metabolism with severe elevation of ICP at mid-gestation. We will contrast these defense strategies to those available to the near term fetal sheep. Neuronally generated nitric oxide may be important in synaptic plasticity during development. Decreased cerebral blood flow with nitric oxide synthase inhibition in postnatal animals suggests that tonic nitric oxide production acts to maintain an elevated level of blood flow. We will determine if development of a nitric oxide dependent mechanism between 90 and 130 days gestation is partly responsible for the tripling of basal blood flow and the amplification of hypoxic and autoregulatory responses. We will characterize the effect of periodic head compression of different amplitudes and durations on cortical and striatal blood flow, metabolism and histopathology in 90 and 130 day fetal sheep in utero. By utilizing antagonists of N-methyl-D-aspartate and quisqualate receptors, and selective immunocytochemical markers of injury in fetal sheep brain, we will evaluate the role of excitotoxic injury known to be prominent in postnatal rats with partial ischemia and hypoxia. Therefore, these studies will provide new insights into developmental mechanisms of cerebrovascular regulation in utero and establish a novel model of perinatal cerebral injury that could occur during labor when homeostatic defense mechanisms fail. The consequences of fetal head compression may have an important bearing on premature and term human newborns predisposed to neurological injury by other prenatal factors, and thereby contribute to cerebral palsy and other neurological disabilities.