Does prenatal immune challenge result in increased extra-axial CSF volume?

摘要 轴外脑脊液体积增大(蛛网膜下腔内的脑脊液)是令人鼓舞的。 神经影像生物标志物用于神经发育障碍(NDDS)的早期检测，尤其是对 自闭症谱系障碍。轴外型脑脊液蓄积与NDDS之间的联系尚不完全清楚。我们 建议母体免疫激活(MIA)可以帮助了解这个问题。临床和动物 研究表明，妊娠期MIA是NDDS的重要病因。米娅是 与母体促炎细胞因子的增加有关，其中一些细胞因子可以跨越 胎盘和胎儿的大脑。与MIA相关的胎儿脑细胞因子环境的变化可能会导致不利的 对神经发育的影响，因为除了免疫功能外，细胞因子在 并参与神经发生和突触发生的调节。一些发现也指出了 MIA如何与脑脊液容量相关的可能途径。细胞因子可增加脑脊液 分泌，细菌内毒素的炎症减少了脑脊液的流量，细胞因子也可能调节 脑膜淋巴-淋巴交换和脑脊液重吸收。在这项研究中，我们建议利用 大量先前从受控饲养中获得的幼猴的神经成像扫描 在婴儿期询问产前炎症事件对EA-CSF容量的影响的条件。我们 假设这些定义明确的侮辱将揭示对脑脊液在脑脊液中积累的选择性影响 蛛网膜下腔，出生后可用结构磁共振进行检测。调查结果将 有助于指导儿科样本中的类似分析，并可能揭示用于儿科的新诊断工具 练习一下。我们的初步结果表明猴子的轴外脑脊液体积显著增加。 产前暴露于细菌内毒素。

Abstract Enlarged extra-axial cerebrospinal fluid volume (CSF in the subarachnoid space) is an encouraging neuroimaging biomarker for the early detection of neurodevelopmental disorders (NDDs), particularly for autism spectrum disorder. The link between extra-axial CSF accumulation and NDDs is not yet fully clear. We propose that maternal immune activation (MIA) can help to inform about this question. Clinical and animal studies implicate MIA during the gestational period as a significant etiological cause of NDDs. MIA is associated with increases in maternal proinflammatory cytokines, and some of these cytokines can cross the placenta and reach the fetal brain. MIA-related changes in the fetal brain cytokine milieu can cause adverse effects on neurodevelopment, because, besides immune function, cytokines have a signaling function in the brain and participate in the regulation of neurogenesis and synaptogenesis. Several findings also point to the possible pathways on how MIA can be associated with CSF volume. The cytokines can increase CSF secretion, inflammation with bacterial endotoxin decreases CSF flow, and cytokines also might modulate the meningeal lymphatic-glymphatic exchange and CSF reabsorption. In this study, we propose to take advantage of a large number of previously acquired neuroimaging scans of young monkeys from controlled rearing conditions to interrogate the impact of prenatal inflammatory events on EA-CSF volume during infancy. We hypothesize that these well-defined insults will reveal selective effects on the accumulation of CSF in subarachnoid space, which can be detected with structural MRI during the postnatal period. The findings will help to guide similar analyses in pediatric samples and may reveal novel diagnostic tools for use in pediatric practice. Our preliminary results suggested a significant increase in extra-axial CSF volum in monkeys prenatally exposed to bacterial endotoxin.