A Mouse Model for Juvenile, Lateral Fluid Percussion Brain Injury Reveals Sex-Dependent Differences in Neuroinflammation and Functional Recovery

Elizabeth A Newell; Brittany P Todd; Zili Luo; Lucy P Evans; Polly J Ferguson; Alexander G Bassuk

doi:10.1089/neu.2019.6675

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A Mouse Model for Juvenile, Lateral Fluid Percussion Brain Injury Reveals Sex-Dependent Differences in Neuroinflammation and Functional Recovery

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A Mouse Model for Juvenile, Lateral Fluid Percussion Brain Injury Reveals Sex-Dependent Differences in Neuroinflammation and Functional Recovery

Elizabeth A Newell, Brittany P Todd, Zili Luo, Lucy P Evans, Polly J Ferguson and Alexander G Bassuk

Journal of neurotrauma, Vol.37(4), pp.635-646

02/15/2020

DOI: 10.1089/neu.2019.6675

PMCID: PMC7045348

PMID: 31621484

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Abstract

Traumatic brain injury (TBI) is a leading cause of death and disability that lacks targeted therapies. Successful translation of promising neuroprotective therapies will likely require more precise identification of target populations through greater study of crucial biological factors like age and sex. A growing body of work supports the impact of these factors on response to and recovery from TBI. However, age and sex are understudied in TBI animal models. The first aim of this study was to demonstrate the feasibility of lateral fluid percussion injury (FPI) in juvenile mice as a model of pediatric TBI. Subsequently, we were interested in examining the impact of young age and sex on TBI outcome. After adapting the lateral FPI model to 21-day-old male and female mice, we characterized the molecular, histological, and functional outcomes. Whereas similar tissue injury was observed in male and female juvenile mice exposed to TBI, we observed differences in neuroinflammation and neurobehavioral function. Overall, our findings revealed less acute inflammatory cytokine expression, greater subacute microglial/macrophage accumulation, and greater neurological recovery in juvenile male mice after TBI. Given that ongoing brain development may affect progression of and recovery from TBI, juvenile models are of critical importance. The sex-dependent differences we discovered after FPI support the necessity of also including this biological variable in future TBI studies. Understanding the mechanisms underlying age- and sex-dependent differences may result in the discovery of novel therapeutic targets for TBI.

age-dependent

neuroinflammation

Original

FPI

function

sex

Details

Title: Subtitle: A Mouse Model for Juvenile, Lateral Fluid Percussion Brain Injury Reveals Sex-Dependent Differences in Neuroinflammation and Functional Recovery
Creators: Elizabeth A Newell - Department of Pediatrics, University of Iowa, Iowa City, Iowa
Brittany P Todd - Department of Pediatrics, University of Iowa, Iowa City, Iowa
Zili Luo - Department of Pediatrics, University of Iowa, Iowa City, Iowa
Lucy P Evans - Department of Pediatrics, University of Iowa, Iowa City, Iowa
Polly J Ferguson - Department of Pediatrics, University of Iowa, Iowa City, Iowa
Alexander G Bassuk - Department of Pediatrics, University of Iowa, Iowa City, Iowa
Resource Type: Journal article
Publication Details: Journal of neurotrauma, Vol.37(4), pp.635-646
DOI: 10.1089/neu.2019.6675
PMID: 31621484
PMCID: PMC7045348
NLM abbreviation: J Neurotrauma
ISSN: 0897-7151
eISSN: 1557-9042
Publisher: Mary Ann Liebert, Inc., publishers
Language: English
Date published: 02/15/2020
Academic Unit: Neurology; Critical Care; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Rheumatology, Allergy, and Immunology; Neurology (Pediatrics)
Record Identifier: 9984070664602771

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