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An exploratory study on the association between blood-based biomarkers and subacute neurometabolic changes following mild traumatic brain injury

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Abstract

Background and objectives

Blood-based biomarkers and advanced neuroimaging modalities such as magnetic resonance spectroscopy (MRS) or diffusion tensor imaging (DTI) have enhanced our understanding of the pathophysiology of mild traumatic brain injury (mTBI). However, there is limited published data on how blood biomarkers relate to neuroimaging biomarkers post-mTBI.

Methods

To investigate this, 30 patients with mTBI and 21 healthy controls were enrolled. Data was collected at two timepoints postinjury: acute, < 24 h, (blood) and subacute, four-to-six weeks, (blood and imaging). Interleukin (IL) 6 and 10 (inflammation), free thiols (systemic oxidative stress) and neurofilament light (NF-L) (axonal injury) were quantified in plasma. The neurometabolites total N-acetyl aspartate (tNAA) (neuronal energetics), Myo-Inositol (Ins) and total Choline (tCh) (inflammation) and, Glutathione (GSH, oxidative stress) were quantified using MRS.

Results

Concentrations of IL-6 and IL-10 were significantly elevated in the acute phase post-mTBI, while NF-L was elevated only in the subacute phase. Total NAA was lowered in patients with mTBI, although this difference was only nominally significant (uncorrected P < 0.05). Within the patient group, acute IL-6 and subacute tNAA levels were negatively associated (r =  − 0.46, uncorrected-P = 0.01), albeit not at a threshold corrected for multiple testing (corrected-P = 0.17). When age was added as a covariate a significant increase in correlation magnitude was observed (ρ =  − 0.54, corrected-P = 0.03).

Conclusion

This study demonstrates potential associations between the intensity of the inflammatory response in the acute phase post-mTBI and neurometabolic perturbations in the subacute phase. Future studies should assess the longitudinal dynamics of blood-based and imaging biomarkers after injury.

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Data availability

The data that support the findings of this study are available on reasonable request to the corresponding author.

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Acknowledgements

We would like to sincerely thank Marian L.C. Bulthuis and Marjan Reinders-Luinge for their valuable technical assistance.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Neurology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands

    Koen Visser, Diana Ciubotariu, Joukje van der Naalt & Harm Jan van der Horn

  2. Department of Neurology, Medisch Spectrum Twente, Koningstraat 1, 7512 KZ, Enschede, The Netherlands

    Myrthe E. de Koning

  3. Department of Radiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands

    Marius G. J. Kok

  4. Department of Neuroscience, BCN Neuroimaging Center, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands

    Anita J. Sibeijn-Kuiper

  5. Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands

    Arno R. Bourgonje

  6. Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands

    Harry van Goor

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  1. Koen Visser
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Contributions

KV: Conceptualization, Methodology, Formal analysis, Data Curation, Writing—Original Draft, Writing—Review and Editing. MEDK: Conceptualization, Investigation, Writing—Review and Editing. DC: Conceptualization, Writing—Review and Editing. MGJK: Investigation, Writing—Review and Editing. AJS-K: Investigation, Writing—Review and Editing. ARB: Conceptualization, Writing—Review and Editing, Supervision. HVG: Conceptualization, Writing—Review and Editing, Supervision. JVDN: Conceptualization, Writing—Review and Editing, Supervision. HJVDH: Conceptualization, Methodology, Formal analysis, Investigation, Writing—Review and Editing, Supervision.

Corresponding author

Correspondence to Harm Jan van der Horn.

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Conflicts of interest

The authors declare no conflicts of interest.

Ethical approval

The AIM-TBI study was approved by the Medical Ethical Committee of the UMCG (METc 2018/681), and all participants provided written informed consent. All study procedures were performed in accordance with the declaration of Helsinki.

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Visser, K., de Koning, M.E., Ciubotariu, D. et al. An exploratory study on the association between blood-based biomarkers and subacute neurometabolic changes following mild traumatic brain injury. J Neurol 271, 1985–1998 (2024). https://doi.org/10.1007/s00415-023-12146-7

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