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Understanding microglial responses in large animal models of traumatic brain injury: an underutilized resource for preclinical and translational research
Journal article   Open access   Peer reviewed

Understanding microglial responses in large animal models of traumatic brain injury: an underutilized resource for preclinical and translational research

Michael R Grovola, Catherine von Reyn, David J Loane and D Kacy Cullen
Journal of neuroinflammation, v 20(1), 67
09 Mar 2023
DOI: https://doi.org/10.1186/s12974-023-02730-z
PMID: 36894951
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1186/s12974-023-02730-zView
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Neuroinflammation Mild TBI Preclinical models Large animal models Microglia
Traumatic brain injury (TBI) often results in prolonged or permanent brain dysfunction with over 2.8 million affected annually in the U.S., including over 56,000 deaths, with over 5 million total survivors exhibiting chronic deficits. Mild TBI (also known as concussion) accounts for over 75% of all TBIs every year. Mild TBI is a heterogeneous disorder, and long-term outcomes are dependent on the type and severity of the initial physical event and compounded by secondary pathophysiological consequences, such as reactive astrocytosis, edema, hypoxia, excitotoxicity, and neuroinflammation. Neuroinflammation has gained increasing attention for its role in secondary injury as inflammatory pathways can have both detrimental and beneficial roles. For example, microglia-resident immune cells of the central nervous system (CNS)-influence cell death pathways and may contribute to progressive neurodegeneration but also aid in debris clearance and neuroplasticity. In this review, we will discuss the acute and chronic role of microglia after mild TBI, including critical protective responses, deleterious effects, and how these processes vary over time. These descriptions are contextualized based on interspecies variation, sex differences, and prospects for therapy. We also highlight recent work from our lab that was the first to describe microglial responses out to chronic timepoints after diffuse mild TBI in a clinically relevant large animal model. The scaled head rotational acceleration of our large animal model, paired with the gyrencephalic architecture and appropriate white:gray matter ratio, allows us to produce pathology with the same anatomical patterns and distribution of human TBI, and serves as an exemplary model to examine complex neuroimmune response post-TBI. An improved understanding of microglial influences in TBI could aid in the development of targeted therapeutics to accentuate positive effects while attenuating detrimental post-injury responses over time.

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19 Record Views
24 citations in Web of Science
24 citations in Scopus

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UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Immunology
Neurosciences
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