Thea Overgaard Wichmann1, Helge Kasch2,3, Stig Dyrskog4, Kristian Høy3,5, Bjarne Kuno Møller6, Jan Krog7, Claus Vinter Bødker Hviid8,9, Hans Jürgen Hoffmann3,10, Mikkel Mylius Rasmussen11,3. 1. Dept. Neurosurgery, Cense-Spine, Aarhus University Hospital, Palle Juul-Jensens, Boulevard 165 8200 Aarhus N, Aarhus, Denmark. Thewic@rm.dk. 2. Dept. Neurology, Aarhus University Hospital, Aarhus, Denmark. 3. Dept. of Clinical Medicine, Aarhus University, Aarhus, Denmark. 4. Dept. Intensive Care, Aarhus University Hospital, Aarhus, Denmark. 5. Dept. Orthopaedic Surgery - Spine section, Aarhus University Hospital, Aarhus, Denmark. 6. Dept. of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark. 7. Dept. Anaesthesiology, Aarhus University Hospital, Aarhus, Denmark. 8. Dept. Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark. 9. Dept. Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark. 10. Dept. Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark. 11. Dept. Neurosurgery, Cense-Spine, Aarhus University Hospital, Palle Juul-Jensens, Boulevard 165 8200 Aarhus N, Aarhus, Denmark.
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.
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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