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Aging disrupts blood–brain and blood-spinal cord barrier homeostasis, but does not increase paracellular permeability
GeroScience ( IF 5.3 ) Pub Date : 2024-10-30 , DOI: 10.1007/s11357-024-01404-9
Mitchell J. Cummins, Ethan T. Cresswell, Renee J. Bevege, Doug W. Smith

Blood-CNS barriers protect the CNS from circulating immune cells and damaging molecules. It is thought barrier integrity becomes disrupted with aging, contributing to impaired CNS function. Using genome-wide and targeted molecular approaches, we found aging affected expression of predominantly immune invasion and pericyte-related genes in CNS regions investigated, especially after middle age, with spinal cord being most impacted. We did not find significant perturbation of endothelial cell junction genes or proteins, nor were vascular density or pericyte coverage affected by aging. We evaluated barrier paracellular permeability using small molecular weight tracers, serum protein extravasation, CNS water content, and iron labelling measures. We found no evidence for age-related increased barrier permeability in any of these tests. We conclude that blood–brain (BBB) and blood-spinal cord barrier (BSCB) paracellular permeability does not increase with normal aging in mouse. Whilst expression changes were not associated with increased permeability, they may represent an age-related primed state whereby additional insults cause increased leakiness.



中文翻译:


衰老会破坏血-脑和血-脊髓屏障稳态,但不会增加细胞旁通透性



血液-CNS 屏障保护 CNS 免受循环免疫细胞和损伤分子的侵害。人们认为屏障完整性会随着年龄的增长而被破坏,导致 CNS 功能受损。使用全基因组和靶向分子方法,我们发现衰老影响了所研究的 CNS 区域中主要免疫侵袭和周细胞相关基因的表达,尤其是在中年之后,脊髓受到的影响最大。我们没有发现内皮细胞连接基因或蛋白质的显着扰动,血管密度或周细胞覆盖率也未受到衰老的影响。我们使用小分子量示踪剂、血清蛋白外渗、 CNS 水分含量和铁标记测量评估屏障细胞旁通透性。我们在这些测试中都没有发现与年龄相关的屏障通透性增加的证据。我们得出结论,小鼠的血-脑 (BBB) 和血-脊髓屏障 (BSCB) 细胞旁通透性不会随着年龄的正常衰老而增加。虽然表达变化与通透性增加无关,但它们可能代表与年龄相关的启动状态,其中额外的侮辱会导致渗漏增加。

更新日期:2024-10-30
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