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The inflammatory response and blood-spinal cord barrier integrity in traumatic spinal cord injury: a prospective pilot study

  • Original Article - Spine trauma
  • Published:
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Abstract

Purpose

Triggering of inflammatory responses and disruption of blood-spinal cord barrier (BSCB) integrity are considered pivotal events in the pathophysiology of traumatic spinal cord injury (TSCI). Yet, these events are poorly understood and described in humans. This study aims to describe inflammatory responses and BSCB integrity in human TSCI.

Methods

Fifteen TSCI patients and fifteen non-TSCI patients were prospectively recruited from Aarhus University Hospital, Denmark. Peripheral blood (PB) and cerebrospinal fluid (CSF) were collected at median day 0 [IQR: 1], median day 9 [IQR: 2], and median day 148 [IQR: 49] after injury. PB and CSF were analyzed for immune cells by flow cytometry, cytokines by multiplex immunoassay, and BSCB integrity by IgG Index.

Results

Eleven TSCI patients completed follow-up. Results showed alterations in innate and adaptive immune cell counts over time. TSCI patients had significantly increased cytokine concentrations in CSF at the first and second follow-up, while only concentrations of interleukin (IL)-4, IL-8, and tumor necrosis factor-α remained significantly increased at the third follow-up. In PB, TSCI patients had significantly increased IL-6, IL-8, and IL-10 concentrations and significantly decreased interferon-γ concentrations at the first follow-up. Results further showed increased IgG Index indicative of BSCB disruption in seven TSCI patients at the first follow-up, five TSCI patients at the second follow-up, and two patients at the third follow-up.

Conclusions

Our results suggest that TSCI mainly triggers innate inflammatory responses that resolves over time, although with some degree of non-resolving inflammation, particularly in CSF. Our results cannot confirm BSCB disruption in all TSCI patients.

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Acknowledgements

We sincerely thank all the patients who volunteered to be included in this study and the staff at Aarhus University Hospital for their participation. We thank Anne-Marie Toft for her support and assistance in performing the Conventional Flow Cytometry analyses. The Imaging Flow Cytometry analyses were performed at the FACS Core Facility at Aarhus University. We thank for their assistance in performing the analyses and interpretation of the results.

Funding

This research was funded by Lundbeckfonden; Aase og Ejnar Danielsens Fond; Grosserer L.F. Foghts Fond; Dagmar Marshalls Fond; A.P. Møller Fonden; Grosserer A.V. Lykfeldt og Hustrus Legat; Jascha Fonden; and UlykkesPatientForeningen.

Author information

Authors and Affiliations

  1. Dept. Neurosurgery, Cense-Spine, Aarhus University Hospital, Palle Juul-Jensens, Boulevard 165 8200 Aarhus N, Aarhus, Denmark

    Thea Overgaard Wichmann & Mikkel Mylius Rasmussen

  2. Dept. Neurology, Aarhus University Hospital, Aarhus, Denmark

    Helge Kasch

  3. Dept. of Clinical Medicine, Aarhus University, Aarhus, Denmark

    Helge Kasch, Kristian Høy, Hans Jürgen Hoffmann & Mikkel Mylius Rasmussen

  4. Dept. Intensive Care, Aarhus University Hospital, Aarhus, Denmark

    Stig Dyrskog

  5. Dept. Orthopaedic Surgery – Spine section, Aarhus University Hospital, Aarhus, Denmark

    Kristian Høy

  6. Dept. of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark

    Bjarne Kuno Møller

  7. Dept. Anaesthesiology, Aarhus University Hospital, Aarhus, Denmark

    Jan Krog

  8. Dept. Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark

    Claus Vinter Bødker Hviid

  9. Dept. Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

    Claus Vinter Bødker Hviid

  10. Dept. Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark

    Hans Jürgen Hoffmann

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  1. Thea Overgaard Wichmann
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Correspondence to Thea Overgaard Wichmann.

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Ethical approval

This research was approved by the Central Denmark Region Committees on Health Research Ethics (1–10-72–382-17) and the Danish Data Protection Agency (1–16-02–754-17) and registered on ClinicalTrials.gov (NCT03505463).

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Wichmann, T.O., Kasch, H., Dyrskog, S. et al. The inflammatory response and blood-spinal cord barrier integrity in traumatic spinal cord injury: a prospective pilot study. Acta Neurochir 164, 3143–3153 (2022). https://doi.org/10.1007/s00701-022-05369-6

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  • DOI: https://doi.org/10.1007/s00701-022-05369-6

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