Johnson Abbie C, Tremble Sarah M, Cipolla Marilyn J
Department of Neurological Sciences, University of Vermont Larner College of Medicine, Burlington, VT, United States.
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Vermont Larner College of Medicine, Burlington, VT, United States.
Front Physiol. 2022 May 9;13:889918. doi: 10.3389/fphys.2022.889918. eCollection 2022.
Preeclampsia (PE) is a hypertensive disorder of pregnancy that is associated with memory impairment, cognitive decline and brain atrophy later in life in women at ages as young as early-to-mid 40 s. PE increases the risk of vascular dementia three-fold, however, long-lasting effects of PE on the vasculature of vulnerable brain regions involved in memory and cognition, such as the hippocampus, remain unknown. Here, we used a rat model of experimental PE (ePE) induced by maintaining rats on a 2% cholesterol diet beginning on day 7 of gestation to investigate hippocampal function later in life. Hippocampal-dependent memory and hippocampal arteriole (HA) function were determined in Sprague Dawley rats 5 months after either a healthy pregnancy or ePE ( = 8/group). Rats that had ePE were hypertensive and had impaired vasoreactivity of HAs to mediators involved in matching neuronal activity with local blood flow (i.e., neurovascular coupling). ePE rats also had impaired long-term memory, but not spatial memory. Thus, this model of ePE mimics some of the long-lasting cardiovascular and cognitive consequences that occur in women who previously had PE. These findings suggest endothelial and vascular smooth muscle dysfunction of HAs were present months after PE that could impair hippocampal neurovascular coupling. This represents a novel vascular mechanism by which PE causes early-onset dementia.
子痫前期（PE）是一种妊娠期高血压疾病，与40岁出头至40多岁中期的女性日后出现的记忆障碍、认知衰退和脑萎缩有关。PE使血管性痴呆的风险增加两倍，然而，PE对参与记忆和认知的脆弱脑区（如海马体）血管系统的长期影响仍不清楚。在此，我们使用了一种实验性PE（ePE）大鼠模型，从妊娠第7天开始让大鼠食用2%胆固醇饮食来研究其日后的海马体功能。在健康妊娠或ePE（每组n = 8）5个月后的斯普拉格-道利大鼠中测定了海马体依赖性记忆和海马体小动脉（HA）功能。患有ePE的大鼠患有高血压，其HA对参与使神经元活动与局部血流相匹配（即神经血管耦合）的介质的血管反应性受损。ePE大鼠的长期记忆也受损，但空间记忆未受损。因此，这种ePE模型模拟了先前患有PE的女性中出现的一些长期心血管和认知后果。这些发现表明，PE数月后HA存在内皮和血管平滑肌功能障碍，这可能会损害海马体神经血管耦合。这代表了一种PE导致早发性痴呆的新血管机制。
