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聚化二乙烯对胎儿血脑屏障的影响:使用微生理系统进行评估

Sourabh Sharma¹, Manuel Vidal^2,3, Souvik Paul¹

¹Division of Basic Science and Translational Research, OBGYN Department, University of Texas Medical Branch at Galveston, Galveston, TX, United States.

Frontiers in cell and developmental biology

|March 27, 2025

概括

这项研究使用人类胎儿血脑屏障模型来表明,聚二乙醇 (PBDE) 导致谷氨酸失调,这是自闭症谱系障碍 (ASD) 的一个因素,而不会引发神经炎症.

科学领域:

神经科学是一个神经科学.
毒理学毒理学毒理学
发展生物学发展生物学

背景情况:

谷氨酸失调和神经炎症与神经系统疾病有关,例如新生儿的自闭症谱系障碍 (ASD).
有限的体外模型阻碍了对产前谷氨酸失调和神经炎症的理解.
聚化乙烯 (PBDE),环境污染物,正在研究它们的神经毒性作用.

研究的目的:

评估PBDE (99和47) 对细胞活力,谷氨酸水平和神经炎症的影响.
为了利用人类胎儿血脑屏障器官芯片 (FB-OOC) 模型的生理相关性.
评估模仿胎盘转移和直接暴露的PBDE效应.

主要方法:

建立了一个人类FB-OOC模型,包括内皮细胞,细胞周细胞和神经元-星细胞-微细胞三培养.
直接或通过胎盘条件介质给药PBDE,以评估对FB-OOC的影响.
试验包括细胞活力 (LDH),谷氨酸水平,细胞因子分析和微质激活标志物 (CD11b,Iba1).

主要成果:

该FB-OOC模型证明了屏障完整性和基线生理功能.
在芯片上的PBDE暴露导致细胞毒性和谷氨酸在神经质共同培养中的上调调节.
与直接2D培养暴露不同的是,在芯片上的PBDE暴露时没有观察到神经炎症和微质激活.

结论:

成功开发了一种功能性的人类胎儿血脑屏障模型.
在这个模型中,PBDE诱导了谷氨酸失调,这是ASD发展的潜在贡献者,独立于神经炎症.
FB-OOC系统为研究产前暴露对神经发育的影响提供了一个有价值的平台.

关键词:

胎儿大脑胎儿大脑谷氨酸酸盐的使用方法器官在芯片上的器官胎盘 - 大脑轴胎盘在芯片上的胎盘

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