Validation and characterization of a novel blood-brain barrier platform for investigating traumatic brain injury.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Blood-Brain Barrier* ; Brain Injuries, Traumatic*; Humans ; Endothelial Cells ; Brain ; Astrocytes

The Blood-Brain Barrier (BBB) is a highly-selective physiologic barrier responsible for maintaining cerebral homeostasis. Innovative in vitro models of the BBB are needed to provide useful insights into BBB function with CNS disorders like traumatic brain injury (TBI). TBI is a multidimensional and highly complex pathophysiological condition that requires intrinsic models to elucidate its mechanisms. Current models either lack fluidic shear stress, or neglect hemodynamic parameters important in recapitulating the human in vivo BBB phenotype. To address these limitations in the field, we developed a fluid dynamic novel platform which closely mimics these parameters. To validate our platform, Matrigel-coated Transwells were seeded with brain microvascular endothelial cells, both with and without co-cultured primary human astrocytes and bone-marrow mesenchymal stem cells. In this article we characterized BBB functional properties such as TEER and paracellular permeability. Our platform demonstrated physiologic relevant decreases in TEER in response to an ischemic environment, while directly measuring barrier fluid fluctuation. These recordings were followed with recovery, implying stability of the model. We also demonstrate that our dynamic platform is responsive to inflammatory and metabolic cues with resultant permeability coefficients. These results indicate that this novel dynamic platform will be a valuable tool for evaluating the recapitulating BBB function in vitro, screening potential novel therapeutics, and establishing a relevant paradigm to evaluate the pathophysiology of TBI.
(© 2023. Springer Nature Limited.)

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T32 GM008792 United States GM NIGMS NIH HHS

Date Created: 20230926 Date Completed: 20230928 Latest Revision: 20231121

20240829

PMC10522590

10.1038/s41598-023-43214-7

37752338