Association of sub-acute changes in plasma amino acid levels with long-term brain pathologies in a rat model of moderate-severe traumatic brain injury

Xuan Vinh To; Abdalla Z Mohamed; Paul Cumming; Fatima A Nasrallah

doi:10.3389/fnins.2022.1014081

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Association of sub-acute changes in plasma amino acid levels with long-term brain pathologies in a rat model of moderate-severe traumatic brain injury

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Association of sub-acute changes in plasma amino acid levels with long-term brain pathologies in a rat model of moderate-severe traumatic brain injury

Xuan Vinh To, Abdalla Z Mohamed, Paul Cumming and Fatima A Nasrallah

Frontiers in Neuroscience, Vol.16, pp.1-16

2023

DOI: https://doi.org/10.3389/fnins.2022.1014081

PMCID: PMC9853432

PMID: 36685246

Appears in Thompson Institute Research Collection

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Abstract

neurite orientation dispersion and density imaging (NODDI)

traumatic brain injury

diffusion magnetic resonance imaging

brain microstructure

amino acids

Other Collaborations

Thompson Institute Special Collection

Introduction: Traumatic brain injury (TBI) induces a cascade of cellular alterations that are responsible for evolving secondary brain injuries. Changes in brain structure and function after TBI may occur in concert with dysbiosis and altered amino acid fermentation in the gut. Therefore, we hypothesized that subacute plasma amino acid levels could predict long term microstructural outcomes as quantified using neurite orientation dispersion and density imaging (NODDI). Methods: Fourteen 8 to10 week old male rats were randomly assigned either to sham (n = 6) or a single moderate severe TBI (n = 8) procedure targeting the primary somatosensory cortex. Venous blood samples were collected at days one, three, seven, and 60 post procedure and NODDI imaging were carried out at day 60. Principal Component Regression analysis was used to identify time dependent plasma amino acid concentrations after in the subacute phase post injury that predicted NODDI metric outcomes at day 60. Results: The TBI group had significantly increased plasma levels of glutamine, arginine, alanine, proline, tyrosine, valine, isoleucine, leucine, and phenylalanine at days three to seven post injury. Higher levels of several neuroprotective amino acids, especially the branched chain amino acids (valine, isoleucine, leucine) and phenylalanine, as well as serine, arginine, and asparagine at days three to seven post injury were also associated with lower isotropic diffusion volume fraction measures in the ventricles and thus lesser ventricular dilation at day 60. Discussion: In the first such study, we examined the relationship between the long term post TBI microstructural outcomes across whole brain and the subacute changes in plasma amino acid concentrations. At days three to seven post injury, we observed that increased plasma levels of several amino acids, particularly the branched chain amino acids and phenylalanine, were associated with lesser degrees of ventriculomegaly and hydrocephalus TBI neuropathology at day 60 post injury. The results imply that altered amino acid fermentation in the gut may mediate neuroprotection in the aftermath of TBI.

Details

Title: Association of sub-acute changes in plasma amino acid levels with long-term brain pathologies in a rat model of moderate-severe traumatic brain injury
Authors: Xuan Vinh To (Author) - The University of Queensland
Abdalla Z Mohamed (Author) - University of the Sunshine Coast, Queensland, Thompson Institute
Paul Cumming (Author) - Queensland University of Technology
Fatima A Nasrallah (Corresponding Author) - The University of Queensland
Publication details: Frontiers in Neuroscience, Vol.16, pp.1-16
Publisher: Frontiers Research Foundation
Date published: 2023
DOI: 10.3389/fnins.2022.1014081
ISSN: 1662-453X
PMID: 36685246; PMC9853432
Copyright note: © 2023 To, Mohamed, Cumming and Nasrallah. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Grant note: 2014000857/ Motor Accident Insurance Commission (MAIC), Queensland Government, Australia
Organisation Unit: University of the Sunshine Coast, Queensland; Thompson Institute
Language: English
Record Identifier: 99705698402621
Output Type: Journal article

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Web Of Science research areas: Neurosciences

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