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Article

A 3D Tissue Model of Traumatic Brain Injury with Excitotoxicity That Is Inhibited by Chronic Exposure to Gabapentinoids

1
Department of Biomedical Engineering, Science and Technology Center, 4 Colby Street, School of Engineering, Tufts University, Medford, MA 02155, USA
2
Department of Biomedical Engineering, Initiative for Neural Science, Disease, and Engineering (INSciDE), Science & Engineering Complex, 200 College Avenue, Tufts University, Medford, MA 02155, USA
3
Department of Biology, Allen Discovery Center at Tufts University, Science & Engineering Complex, 200 College, Avenue, Medford, MA 021553, USA
4
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(8), 1196; https://doi.org/10.3390/biom10081196
Received: 11 June 2020 / Revised: 10 August 2020 / Accepted: 12 August 2020 / Published: 17 August 2020
(This article belongs to the Special Issue Biological Biomaterials for Regenerative Medicine)
Injury progression associated with cerebral laceration is insidious. Following the initial trauma, brain tissues become hyperexcitable, begetting further damage that compounds the initial impact over time. Clinicians have adopted several strategies to mitigate the effects of secondary brain injury; however, higher throughput screening tools with modular flexibility are needed to expedite mechanistic studies and drug discovery that will contribute to the enhanced protection, repair, and even the regeneration of neural tissues. Here we present a novel bioengineered cortical brain model of traumatic brain injury (TBI) that displays characteristics of primary and secondary injury, including an outwardly radiating cell death phenotype and increased glutamate release with excitotoxic features. DNA content and tissue function were normalized by high-concentration, chronic administrations of gabapentinoids. Additional experiments suggested that the treatment effects were likely neuroprotective rather than regenerative, as evidenced by the drug-mediated decreases in cell excitability and an absence of drug-induced proliferation. We conclude that the present model of traumatic brain injury demonstrates validity and can serve as a customizable experimental platform to assess the individual contribution of cell types on TBI progression, as well as to screen anti-excitotoxic and pro-regenerative compounds. View Full-Text
Keywords: traumatic brain injury; tissue engineering; excitotoxicity; 3D neural tissues; voltage-gated calcium channels traumatic brain injury; tissue engineering; excitotoxicity; 3D neural tissues; voltage-gated calcium channels
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MDPI and ACS Style

Rouleau, N.; Bonzanni, M.; Erndt-Marino, J.D.; Sievert, K.; Ramirez, C.G.; Rusk, W.; Levin, M.; Kaplan, D.L. A 3D Tissue Model of Traumatic Brain Injury with Excitotoxicity That Is Inhibited by Chronic Exposure to Gabapentinoids. Biomolecules 2020, 10, 1196. https://doi.org/10.3390/biom10081196

AMA Style

Rouleau N, Bonzanni M, Erndt-Marino JD, Sievert K, Ramirez CG, Rusk W, Levin M, Kaplan DL. A 3D Tissue Model of Traumatic Brain Injury with Excitotoxicity That Is Inhibited by Chronic Exposure to Gabapentinoids. Biomolecules. 2020; 10(8):1196. https://doi.org/10.3390/biom10081196

Chicago/Turabian Style

Rouleau, Nicolas, Mattia Bonzanni, Joshua D. Erndt-Marino, Katja Sievert, Camila G. Ramirez, William Rusk, Michael Levin, and David L. Kaplan. 2020. "A 3D Tissue Model of Traumatic Brain Injury with Excitotoxicity That Is Inhibited by Chronic Exposure to Gabapentinoids" Biomolecules 10, no. 8: 1196. https://doi.org/10.3390/biom10081196

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