Hippocampal arteriole remodeling and brain injury in preeclampsia and eclampsia
先兆子痫和子痫的海马小动脉重塑和脑损伤
基本信息
- 批准号:10163278
- 负责人:
- 金额:$ 39万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-01 至 2023-05-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAgingAlzheimer&aposs DiseaseAnimalsArteriesBehavioralBlood VesselsBlood flowBrainBrain InjuriesBrain regionCardiovascular DiseasesCell DeathCerebrovascular CirculationCerebrovascular DisordersCognitionCognitive deficitsDevelopmentEclampsiaExperimental ModelsFunctional disorderGlutamatesGoalsHeartHippocampus (Brain)HyperactivityHyperemiaHyperlipidemiaHypertensionHypoxiaImmunohistochemistryImpaired cognitionImpairmentInjuryLeadLesionLifeLinkMagnetic Resonance ImagingMaternal MortalityMeasuresMemoryMicrocirculationMorbidity - disease rateMyocardial InfarctionNatureNeuronal InjuryNeuronsNeurotransmittersOnset of illnessOutcomeOxidative StressOxygenPathway interactionsPeripheralPhysiologic pulsePostpartum PeriodPre-EclampsiaPredispositionPregnancyRattusRecurrenceRiskRoleSeizuresStructureTestingTravelTreesVascular DiseasesVascular blood supplyVascular remodelingVascular resistanceWomanarteriolecerebral atrophycognitive changecognitive testingdisorder riskearly onsetendothelial dysfunctionexcitotoxicityexperimental studyfetalimprovedin vivoischemic injurylong short term memorylong term memorymaternal morbiditymild cognitive impairmentmorris water mazemortalitynew therapeutic targetnovelobject recognitionoxidized low density lipoproteinparenchymal arteriolespregnancy disorderpregnantpressurepreventresponsestroke risktherapeutic targettissue oxygenationway findingwhite matter
项目摘要
Preeclampsia (PE) is a common hypertensive disorder of pregnancy that causes significant maternal and fetal
morbidity and mortality worldwide. The consequences of PE extend far beyond pregnancy and are associated
with excessive cardiovascular and cerebrovascular disease risk later in life, including a 9-fold increased risk of
dying from myocardial infarction and a 4- to 5-fold increased risk of stroke. PE women also have high seizure
susceptibility (called eclampsia) that causes considerable morbidity and mortality both during seizure and later
in life. Importantly, former PE and eclamptic women (seizure in a PE woman) have poorer cognition and brain
atrophy later in life, with increased white matter lesions on magnetic resonance imaging (MRI) that positively
correlate with cognitive defects and decline. The effect of PE and eclampsia on memory and cognition
suggests the hippocampus is adversely affected, a brain region that has a critical role in consolidation of long-
and short-term memory and spatial navigation. Our previous studies found that hippocampal arterioles (HAs),
small brain arterioles that perfuse the hippocampus, were smaller and stiffer in a model of experimental PE
(ePE) than HAs from normal late-pregnant animals that was associated with mild cognitive impairment. In
addition, ePE animals lacked a hyperemic response to seizure that was associated with greater neuronal
injury. Thus, the overall goal of this proposal is to investigate vascular mechanisms of hippocampal injury and
cognitive impairment during PE and eclampsia. The overall hypothesis of this application is that HA remodeling
and increased stiffness during ePE causes hippocampal injury that promotes cognitive impairment. We will
therefore investigate mechanisms by which HA remodeling and increased stiffness occurs in ePE and if
preventing the vascular changes will prevent cognitive impairment (Aim 1). We will also determine the effect of
prolonged and recurrent seizure on hippocampal injury and if preventing HA remodeling will prevent injury
during seizure (Aim 2). And lastly, we will determine if the vascular and cognitive changes persist long-term
(months postpartum) in ePE rats (Aim 3). The proposed studies will provide a greater understanding of the
mechanisms by which cognitive impairment occurs in women with PE and how seizure adversely affects the
maternal brain. The potential outcome of this project is identifying new therapeutic targets and strategies for
preventing and/or treating hippocampal injury in women with PE and eclampsia that could improve the lives of
women with this condition.
先兆子痫 (PE) 是一种常见的妊娠期高血压疾病,可导致严重的母婴并发症
全世界的发病率和死亡率。 PE 的后果远远超出了怀孕范围,并且与
晚年罹患心脑血管疾病的风险过高,其中罹患心脑血管疾病的风险增加 9 倍
死于心肌梗塞,中风的风险增加 4 至 5 倍。女性体育运动癫痫发作率也很高
易感性(称为子痫),在癫痫发作期间和之后会导致相当大的发病率和死亡率
在生活中。重要的是,曾经患有PE和子痫的女性(PE女性癫痫发作)的认知能力和大脑较差
晚年萎缩,磁共振成像(MRI)显示白质病变增加,这表明
与认知缺陷和衰退相关。 PE和子痫对记忆和认知的影响
表明海马体受到不利影响,该大脑区域在巩固长期记忆中发挥着关键作用。
以及短期记忆和空间导航。我们之前的研究发现海马小动脉(HAs),
在实验性 PE 模型中,灌注海马体的小脑动脉更小、更僵硬
(ePE) 高于正常妊娠晚期动物的 HA,且与轻度认知障碍相关。在
此外,ePE 动物缺乏与更大的神经元相关的癫痫发作充血反应。
受伤。因此,该提案的总体目标是研究海马损伤的血管机制和
PE 和子痫期间的认知障碍。本申请的总体假设是 HA 重塑
ePE 期间僵硬增加会导致海马损伤,从而导致认知障碍。我们将
因此,研究 ePE 中 HA 重塑和刚度增加的机制,如果
预防血管变化将预防认知障碍(目标 1)。我们还将确定效果
海马损伤引起的长期和反复发作,如果阻止 HA 重塑就可以预防损伤
癫痫发作期间(目标 2)。最后,我们将确定血管和认知变化是否长期持续
(产后几个月)在 ePE 大鼠中(目标 3)。拟议的研究将有助于人们更好地了解
患有PE的女性发生认知障碍的机制以及癫痫发作如何对认知障碍产生不利影响
母亲的大脑。该项目的潜在成果是确定新的治疗靶点和策略
预防和/或治疗患有先兆子痫和子痫的女性的海马损伤,可以改善患者的生活
患有这种病症的女性。
项目成果
期刊论文数量(0)
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Marilyn J Cipolla其他文献
Marilyn J Cipolla的其他文献
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{{ truncateString('Marilyn J Cipolla', 18)}}的其他基金
Hippocampal arteriole remodeling and brain injury in preeclampsia and eclampsia
先兆子痫和子痫的海马小动脉重塑和脑损伤
- 批准号:
9919008 - 财政年份:2018
- 资助金额:
$ 39万 - 项目类别:
Hippocampal arteriole remodeling and brain injury in preeclampsia and eclampsia
先兆子痫和子痫的海马小动脉重塑和脑损伤
- 批准号:
9765427 - 财政年份:2018
- 资助金额:
$ 39万 - 项目类别:
Hippocampal arteriole remodeling and brain injury in preeclampsia and eclampsia
先兆子痫和子痫的海马小动脉重塑和脑损伤
- 批准号:
10404042 - 财政年份:2018
- 资助金额:
$ 39万 - 项目类别:
Targeting Parenchymal Arterioles in Acute Stroke Treatment
急性中风治疗中的靶向实质小动脉
- 批准号:
9266499 - 财政年份:2015
- 资助金额:
$ 39万 - 项目类别:
Targeting pial collaterals for acute stroke treatment
针对急性中风治疗的软脑膜侧支循环
- 批准号:
10592439 - 财政年份:2015
- 资助金额:
$ 39万 - 项目类别:
Targeting pial collaterals for acute stroke treatment
针对急性中风治疗的软脑膜侧支循环
- 批准号:
10412122 - 财政年份:2015
- 资助金额:
$ 39万 - 项目类别:
Targeting pial collaterals for acute stroke treatment
针对急性中风治疗的软脑膜侧支循环
- 批准号:
10309056 - 财政年份:2015
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$ 39万 - 项目类别:
Cerebrovascular Function during Ischemia and Reperfusion
缺血和再灌注期间的脑血管功能
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7998847 - 财政年份:2010
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Cerebral Arteriole Function during Hyperglycemic Stroke
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6973905 - 财政年份:2005
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$ 39万 - 项目类别:
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