Vascular Physiology Laboratory, Department of Basic Sciences, Universidad del Bio-Bio, Chillán, Chile.
Department of Clinical Sciences, Faculty of Veterinary Sciences, Universidad de Concepción, Chillán, Chile.
J Cereb Blood Flow Metab. 2022 Dec;42(12):2318-2332. doi: 10.1177/0271678X221121872. Epub 2022 Aug 25.
Children born from women with preeclampsia have alterations in cerebral neurovascular development and a high risk for developing cognitive alterations. Because cerebral blood vessels are critical components in cerebrovascular development, we evaluated the brain microvascular perfusion and microvascular reactivity (exposed to external stimuli of warm and cold) in pups born to preeclampsia-like syndrome based on the reduction of uterine perfusion (RUPP). Also, we evaluate the angiogenic proteomic profile in those brains. Pregnant mice showed a reduction in uterine flow after RUPP surgery (-40 to 50%) associated with unfavorable perinatal results compared to sham mice. Furthermore, offspring of the RUPP mice exhibited reduced brain microvascular perfusion at postnatal day 5 (P5) compared with offspring from sham mice. This reduction was preferentially observed in females. Also, brain microvascular reactivity to external stimuli (warm and cold) was reduced in pups of RUPP mice. Furthermore, a differential expression of the angiogenic profile associated with inflammation, extrinsic apoptotic, cancer, and cellular senescence processes as the primary signaling impaired process was found in the brains of RUPP-offspring. Then, offspring (P5) from preeclampsia-like syndrome exhibit impaired brain perfusion and microvascular reactivity, particularly in female mice, associated with differential expression of angiogenic proteins in the brain tissue.
患有先兆子痫的女性所生的孩子,其大脑神经血管发育会出现改变,并且发生认知改变的风险很高。由于脑血管是脑血管发育的关键组成部分,我们评估了基于子宫灌注减少的子痫前期样综合征的幼仔的脑微血管灌注和微血管反应性(对温暖和寒冷的外部刺激做出反应)。此外,我们还评估了这些大脑中的血管生成蛋白质组特征。与 sham 组相比,RUPP 手术后,怀孕的小鼠子宫血流减少(减少 40%至 50%),与不良围产期结果相关。此外,与 sham 组的后代相比,RUPP 组幼仔在出生后第 5 天(P5)的脑微血管灌注减少。这种减少主要在雌性中观察到。此外,RUPP 小鼠的幼仔对外部刺激(温暖和寒冷)的脑微血管反应性降低。此外,在 RUPP 后代的脑组织中发现了与炎症、外在凋亡、癌症和细胞衰老过程相关的血管生成特征的差异表达,这是主要受损的信号转导过程。然后,患有子痫前期样综合征的后代(P5)表现出脑灌注和微血管反应性受损,尤其是在雌性小鼠中,这与脑组织中血管生成蛋白的差异表达有关。