Cerebrovascular changes in pregnancy and hypertension

妊娠期脑血管变化与高血压

• 批准号: 8113685
• 负责人: Marilyn J Cipolla
• 金额: $ 7.58万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8113685
• 关键词: Acute; Address; Affect; Animals; Blindness; Blood - brain barrier anatomy; Blood Circulation; Blood Pressure; Brain; Brain Edema; Cause of Death; Cell Membrane Permeability; Cerebral Edema; Cerebrovascular Circulation; Cerebrum; Cessation of life; Clinical; Convulsions; Dilatation - action; Eclampsia; Edema; Endothelial Cells; Event; Growth Factor; Headache; Health; Homeostasis; Hormonal; Hormones; Hydrostatic Pressure; Hypertension; Hypertensive Encephalopathy; Impairment; In Vitro; Life; Measurement; Measures; Mediating; Microspheres; Modeling; Nausea; Neurologic; Organ; PGF gene; Patients; Permeability; Placental Growth Factor; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Production; Property; Relaxin; Resistance; Role; Structure; Techniques; Tight Junctions; Time; Unconscious State; Vascular remodeling; Visual; Vomiting; Woman; arteriole; cerebrovascular; clinically relevant; fetal; hemodynamics; in vitro Model; in vivo; in vivo Model; lucifer yellow; medical complication; neuroimaging; novel; pregnancy hypertension; pregnant; pressure; public health relevance; research study; response; transmission process; venule

DESCRIPTION (provided by applicant): Eclampsia is a serious complication of pregnancy that occurs when hypertension during pregnancy develops with neurologic complications, including headache, vomiting, blindness and convulsions. While multiple organs are affected by hypertension in pregnancy, cerebrovascular involvement is the direct cause of death in ~40% of patients. The major cerebrovascular changes that occur during eclampsia are thought to be similar to hypertensive encephalopathy in which acute elevations in pressure cause autoregulatory breakthrough, hyperperfusion and edema. Our preliminary studies found that late-pregnant animals had significantly decreased cerebrovascular resistance and hyperperfusion compared to nonpregnant animals during acute hypertension, similar to eclampsia. Importantly, only the late-pregnant animals developed cerebral edema, suggesting that pregnancy alone predisposes the brain to the neurologic complications of eclampsia when blood pressure is elevated. Because of the prominent role of edema formation in mediating the neurologic complications of eclampsia, the long-term objective of this project is understand the underlying mechanisms by which pregnancy and hypertension in pregnancy affect the cerebral circulation in a way that promotes hydrostatic brain edema during increased blood pressure. Our preliminary studies suggest for the first time that pregnancy causes outward remodeling of cerebral arterioles, an effect that likely diminishes small vessel resistance in the brain during acute hypertension. Aim 1 will therefore investigate underlying mechanisms by which pregnancy causes outward remodeling, including the hormone relaxin, known to promote vascular remodeling in the systemic circulation during pregnancy. We also found that pregnancy causes more severe blood-brain barrier disruption in response to acute hypertension compared to nonpregnant animals. Aim 2 will investigate underlying mechanisms by which this occurs, including production of placental growth factor that can increase hydraulic conductivity and decrease tight junction expression. Lastly, because many women who develop eclampsia have preexisting hypertension, or preeclampsia, prior to the acute hypertensive event that causes neurologic complications, Aim 3 will use a model of hypertension in pregnancy to investigate changes in cerebral hemodynamics, blood-brain barrier properties and edema formation that may be unique compared to normal pregnancy. A powerful combination of in vivo and in vitro techniques will be used that should provide clinically relevant information regarding novel hemodynamic changes and mechanisms of edema during pregnancy and hypertension in pregnancy. PUBLIC HEALTH RELEVANCE: Eclampsia is a leading cause of maternal death world-wide. These studies investigate underlying mechanisms by which pregnancy and hypertension during pregnancy affect the cerebral circulation in ways that promote the neurologic complications of eclampsia. This understanding is crucial to effective management and treatment of this devastating condition.

描述（由申请人提供）：eClampsia是一种严重的怀孕并发症，当怀孕期间的高血压患有神经系统并发症，包括头痛，呕吐，失明和抽搐。虽然多个器官受到怀孕高血压的影响，但脑血管受累是约40％的患者死亡的直接原因。 e子症期间发生的主要脑血管变化被认为类似于高血压性脑病，在高血压脑病中，压力急性升高会导致自动调节性突破，过度灌注和水肿。我们的初步研究发现，与急性高血压期间的非怀孕动物相比，晚期妊娠动物与急性高血压相比，脑血管抵抗和灌注过度显着降低。重要的是，只有晚期诊断的动物出现大脑水肿，这表明仅怀孕就会使大脑在血压升高时会使大脑患有eClampsia的神经系统并发症。由于水肿形成在介导eClampsia的神经系统并发症中的重要作用，因此该项目的长期目标是了解妊娠妊娠和高血压在增加血压期间促进液压脑水肿的基本机制。我们的初步研究表明，怀孕首次导致脑小动物的外部重塑，这种作用可能会在急性高血压期间降低大脑中的小血管耐药性。因此，AIM 1将调查怀孕导致外部重塑的潜在机制，包括激素松弛素，已知可在妊娠期间促进全身循环中的血管重塑。我们还发现，与未怀孕的动物相比，妊娠对急性高血压会导致更严重的血脑屏障破坏。 AIM 2将研究发生这种情况的潜在机制，包括产生胎盘生长因子，该因子可以增加液压电导率并降低紧密的连接表达。最后，由于许多患有急诊症的女性在引起神经系统并发症的急性高血压事件之前具有已经存在的高血压或先兆子痫，因此AIM 3将使用妊娠中的高血压模型来研究脑血流障碍，血液障碍性障碍物的变化，血液 - 脑障碍性质和湿疹的形成可能与正常怀孕相比。将使用体内和体外技术的强大组合，该组合应提供有关新型血液动力学变化和怀孕期间湿气机制的临床相关信息。公共卫生相关性：eclampsia是全球孕产妇死亡的主要原因。这些研究调查了妊娠期间怀孕和高血压影响脑循环的潜在机制，其方式促进了eclampsia的神经系统并发症。这种理解对于有效的管理和治疗这种毁灭性的状况至关重要。