Development of a novel bioengineered 3D brain-like tissue for studying primary blast-induced traumatic brain injury.

RRID:AB_1074620 RRID:AB_225675 RRID:AB_2633275 RRID:AB_2633281 RRID:AB_2762845 RRID:AB_2921338 RRID:AB_2921339 RRID:CVCL_9115 RRID:CVCL_II76 RRID:SCR_001622 RRID:SCR_002798 RRID:SCR_003070 RRID:SCR_008426 RRID:SCR_017377 RRID:SCR_018163 RRID:SCR_019732 biomarkers blast brain injuries cell culture techniques coculture techniques traumatic

Journal

Journal of neuroscience research
ISSN: 1097-4547
Titre abrégé: J Neurosci Res
Pays: United States
ID NLM: 7600111

Informations de publication

Date de publication:
01 2023
Historique:
revised: 04 08 2022
received: 28 04 2022
accepted: 29 08 2022
pubmed: 7 10 2022
medline: 25 11 2022
entrez: 6 10 2022
Statut: ppublish

Résumé

Primary blast injury is caused by the direct impact of an overpressurization wave on the body. Due to limitations of current models, we have developed a novel approach to study primary blast-induced traumatic brain injury. Specifically, we employ a bioengineered 3D brain-like human tissue culture system composed of collagen-infused silk protein donut-like hydrogels embedded with human IPSC-derived neurons, human astrocytes, and a human microglial cell line. We have utilized this system within an advanced blast simulator (ABS) to expose the 3D brain cultures to a blast wave that can be precisely controlled. These 3D cultures are enclosed in a 3D-printed surrogate skull-like material containing media which are then placed in a holder apparatus inside the ABS. This allows for exposure to the blast wave alone without any secondary injury occurring. We show that blast induces an increase in lactate dehydrogenase activity and glutamate release from the cultures, indicating cellular injury. Additionally, we observe a significant increase in axonal varicosities after blast. These varicosities can be stained with antibodies recognizing amyloid precursor protein. The presence of amyloid precursor protein deposits may indicate a blast-induced axonal transport deficit. After blast injury, we find a transient release of the known TBI biomarkers, UCHL1 and NF-H at 6 h and a delayed increase in S100B at 24 and 48 h. This in vitro model will enable us to gain a better understanding of clinically relevant pathological changes that occur following primary blast and can also be utilized for discovery and characterization of biomarkers.

Identifiants

pubmed: 36200530
doi: 10.1002/jnr.25123
doi:

Substances chimiques

Amyloid beta-Protein Precursor 0

Types de publication

Journal Article Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

3-19

Informations de copyright

© 2022 Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

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Auteurs

Dustin M Snapper (DM)

Department of Pharmacology and Molecular Therapeutics, Uniformed Services University, Bethesda, Maryland, USA.

Bianca Reginauld (B)

Department of Pharmacology and Molecular Therapeutics, Uniformed Services University, Bethesda, Maryland, USA.

Volha Liaudanskaya (V)

Department of Biomedical Engineering, Tufts University, Medford, Massachusetts, USA.

Vincent Fitzpatrick (V)

Department of Biomedical Engineering, Tufts University, Medford, Massachusetts, USA.

Yeonho Kim (Y)

Preclinical Behavior and Modeling Core, Uniformed Services University, Bethesda, Maryland, USA.

Irene Georgakoudi (I)

Department of Biomedical Engineering, Tufts University, Medford, Massachusetts, USA.

David L Kaplan (DL)

Department of Biomedical Engineering, Tufts University, Medford, Massachusetts, USA.

Aviva J Symes (AJ)

Department of Pharmacology and Molecular Therapeutics, Uniformed Services University, Bethesda, Maryland, USA.

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