Department of Neurological Sciences, University of Vermont Larner College of Medicine, Burlington, VT, USA.
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Vermont Larner College of Medicine, Burlington, VT, USA.
J Cereb Blood Flow Metab. 2022 Aug;42(8):1425-1436. doi: 10.1177/0271678X221080092. Epub 2022 Feb 9.
Preeclampsia (PE) is a hypertensive disorder of pregnancy associated with neurovascular dysfunction, cognitive impairment and increased seizure susceptibility. Here, we sought to determine if treatment of experimental PE (ePE) rats with apocynin could prevent hippocampal arteriolar (HA) dysfunction and impaired seizure-induced hyperemia within the hippocampus, a brain region central to cognition and seizure generation. Isolated and pressurized HAs from Sprague Dawley rats that were normal pregnant (Preg; n = 8), ePE (n = 8) or ePE treated with apocynin for 2 weeks of gestation (ePE + apo; n = 8) were compared. Hippocampal blood flow (n = 6/group) was measured using hydrogen clearance before and during seizure. Aorta elastin was quantified using histochemistry. ePE was associated with HA dysfunction including reduced contraction to endothelin-1 and diminished dilation to the endothelium-dependent vasodilator NS309 that was prevented by apocynin. However, apocynin had no effect on ePE-induced impairment of dilation to the nitric oxide donor sodium nitroprusside, but increased myogenic tone and substantially increased HA distensibility. Seizure-induced hyperemia was impaired in ePE rats that was restored by apocynin. Aorta from ePE rats had reduced elastin content, suggesting large artery stiffness, that was unaffected by apocynin. Thus, while apocynin partially prevented HA dysfunction, its restoration of functional hyperemia may be protective of seizure-induced injury during eclampsia.
子痫前期 (PE) 是一种与神经血管功能障碍、认知障碍和癫痫易感性增加相关的妊娠高血压疾病。在这里，我们试图确定用 apocynin 治疗实验性 PE (ePE) 大鼠是否可以预防海马血管（HA）功能障碍和海马内癫痫诱导性充血受损，海马是认知和癫痫发作的关键脑区。我们比较了来自正常妊娠（Preg；n=8）、ePE（n=8）或 ePE 用 apocynin 治疗 2 周妊娠（ePE+apo；n=8）的 Sprague Dawley 大鼠的分离和加压 HA。使用氢清除法在癫痫发作前后测量海马血流量（n=6/组）。使用组织化学量化主动脉弹性蛋白。ePE 与 HA 功能障碍有关，包括内皮素-1 引起的收缩减少和内皮依赖性血管扩张剂 NS309 引起的扩张减弱，apocynin 可预防这些功能障碍。然而，apocynin 对 ePE 诱导的一氧化氮供体硝普钠扩张无影响，但增加了血管平滑肌张力并大大增加了 HA 的可扩张性。ePE 大鼠的癫痫诱导性充血受损，apocynin 可恢复。ePE 大鼠的主动脉弹性蛋白含量减少，表明大动脉僵硬，apocynin 对此无影响。因此，虽然 apocynin 部分预防了 HA 功能障碍，但它对功能性充血的恢复可能对子痫期间的癫痫诱导损伤具有保护作用。
