The blood-brain barrier (BBB) is the multicellular interface located between the peripheral circulation and the brain parenchyma. BBB dysfunction is reported in many CNS diseases, such cognitive impairment, depression, Alzheimer’s disease (AD), and multiple sclerosis (MS). Emerging evidence indicates that liver-derived inflammatory mediators are upregulated in neurological diseases with BBB dysfunction. Serum amyloid A (SAA), an acute phase protein secreted by hepatocytes, could be a candidate inflammatory signaling molecule transmitted from the liver to the brain; however, its contribution to BBB dysfunction is poorly understood. The present study aimed to elucidate the involvement of SAA in BBB impairment in an in vitro BBB model using rat brain microvascular endothelial cells (RBECs). We demonstrated that Apo-SAA significantly decreased transendothelial electrical resistance (TEER) and increased sodium fluorescein (Na-F) permeability in RBEC monolayers. Apo-SAA also decreased claudin-5 expression levels in RBECs. Furthermore, the Apo-SAA-mediated impairment of the BBB with decreased claudin-5 expression was inhibited by the addition of a high-density lipoprotein (HDL) related to SAA in plasma. These findings suggest that HDL counteracts the effects of SAA on BBB function. Therefore, the functional imbalance between SAA and HDL may induce BBB impairment, thereby triggering development of neuroinflammation. SAA could be a significant endogenous mediator in the liver-to-brain inflammation axis.

血脑屏障（BBB）是位于外周循环和脑实质之间的多细胞界面。在许多中枢神经系统疾病中，如认知障碍，抑郁，阿尔茨海默氏病（AD）和多发性硬化症（MS），都有BBB功能障碍的报道。越来越多的证据表明，肝源性炎症介质在BBB功能障碍的神经系统疾病中被上调。血清淀粉样蛋白A（SAA）是肝细胞分泌的一种急性期蛋白，可能是从肝脏传播到大脑的候选炎症信号分子。然而，其对血脑屏障功能障碍的贡献知之甚少。本研究旨在阐明使用大鼠脑微血管内皮细胞（RBEC）的体外BBB模型中SAA与BBB损伤的关系。我们证明，Apo-SAA在RBEC单层中显着降低了跨内皮电阻（TEER），并增加了荧光素钠（Na-F）的渗透性。Apo-SAA还降低了RBEC中claudin-5的表达水平。此外，血浆中与SAA相关的高密度脂蛋白（HDL）的添加抑制了Apo-SAA介导的BBB的claudin-5表达降低。这些发现表明，HDL抵消了SAA对BBB功能的影响。因此，SAA和HDL之间的功能失衡可能会诱发BBB损伤，从而触发神经炎症的发展。SAA可能是肝到脑炎症轴的重要内源性介质。Apo-SAA还降低了RBEC中claudin-5的表达水平。此外，血浆中与SAA相关的高密度脂蛋白（HDL）的添加抑制了Apo-SAA介导的BBB的claudin-5表达降低。这些发现表明，HDL抵消了SAA对BBB功能的影响。因此，SAA和HDL之间的功能失衡可能会诱发BBB损伤，从而触发神经炎症的发展。SAA可能是肝到脑炎症轴的重要内源性介质。Apo-SAA还降低了RBEC中claudin-5的表达水平。此外，血浆中与SAA相关的高密度脂蛋白（HDL）的添加抑制了Apo-SAA介导的BBB的claudin-5表达降低。这些发现表明，HDL抵消了SAA对BBB功能的影响。因此，SAA和HDL之间的功能失衡可能会诱发BBB损伤，从而触发神经炎症的发展。SAA可能是肝到脑炎症轴的重要内源性介质。SAA和HDL之间的功能失衡可能会诱发BBB损伤，从而触发神经炎症的发展。SAA可能是肝到脑炎症轴的重要内源性介质。SAA和HDL之间的功能失衡可能会诱发BBB损伤，从而引发神经炎症的发展。SAA可能是肝到脑炎症轴的重要内源性介质。