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

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

Front Neurosci. 2023 Jan 6:16:1014081. doi: 10.3389/fnins.2022.1014081. eCollection 2022.

Authors

Xuan Vinh To¹, Abdalla Z Mohamed^{1

2}, Paul Cumming^{3

4}, Fatima A Nasrallah^{1

5}

Affiliations

¹ The Queensland Brain Institute, The University of Queensland, Saint Lucia, QLD, Australia.
² Thompson Institute, University of the Sunshine Coast, Sunshine Coast, QLD, Australia.
³ Department of Nuclear Medicine, Bern University Hospital, Bern, Switzerland.
⁴ School of Psychology and Counselling, Queensland University of Technology, Brisbane, QLD, Australia.
⁵ Centre for Advanced Imaging, The University of Queensland, Saint Lucia, QLD, Australia.

Abstract

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 8-10-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-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-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.

Keywords: amino acids; brain microstructure; diffusion magnetic resonance imaging; neurite orientation dispersion and density imaging (NODDI); traumatic brain injury.