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- Gard, Anna, et al.
(författare)
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Cerebrospinal fluid levels of neuroinflammatory biomarkers are increased in athletes with persistent post-concussive symptoms following sports-related concussion
- 2023
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Ingår i: Journal of Neuroinflammation. - : Springer Nature. - 1742-2094. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- A sports-related concussion (SRC) is often caused by rapid head rotation at impact, leading to shearing and stretching of axons in the white matter and initiation of secondary inflammatory processes that may exacerbate the initial injury. We hypothesized that athletes with persistent post-concussive symptoms (PPCS) display signs of ongoing neuroinflammation, as reflected by altered profiles of cerebrospinal fluid (CSF) biomarkers, in turn relating to symptom severity. We recruited athletes with PPCS preventing sports participation as well as limiting work, school and/or social activities for ≥ 6 months for symptom rating using the Sport Concussion Assessment Tool, version 5 (SCAT-5) and for cognitive assessment using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Following a spinal tap, we analysed 27 CSF inflammatory biomarkers (pro-inflammatory chemokines and cytokine panels) by a multiplex immunoassay using antibodies as electrochemiluminescent labels to quantify concentrations in PPCS athletes, and in healthy age- and sex-matched controls exercising ≤ 2 times/week at low-to-moderate intensity. Thirty-six subjects were included, 24 athletes with PPCS and 12 controls. The SRC athletes had sustained a median of five concussions, the most recent at a median of 17 months prior to the investigation. CSF cytokines and chemokines levels were significantly increased in eight (IL-2, TNF-α, IL-15, TNF-β, VEGF, Eotaxin, IP-10, and TARC), significantly decreased in one (Eotaxin-3), and unaltered in 16 in SRC athletes when compared to controls, and two were un-detectable. The SRC athletes reported many and severe post-concussive symptoms on SCAT5, and 10 out of 24 athletes performed in the impaired range (Z < − 1.5) on cognitive testing. Individual biomarker concentrations did not strongly correlate with symptom rating or cognitive function. Limitations include evaluation at a single post-injury time point in relatively small cohorts, and no control group of concussed athletes without persisting symptoms was included. Based on CSF inflammatory marker profiling we find signs of ongoing neuroinflammation persisting months to years after the last SRC in athletes with persistent post-concussive symptoms. Since an ongoing inflammatory response may exacerbate the brain injury these results encourage studies of treatments targeting the post-injury inflammatory response in sports-related concussion.
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| 2. |
- Gard, Anna, et al.
(författare)
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Widespread White Matter Abnormalities in Concussed Athletes Detected by 7T Diffusion Magnetic Resonance Imaging
- 2024
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc.. - 0897-7151 .- 1557-9042.
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Tidskriftsartikel (refereegranskat)abstract
- Sports-related concussions may cause white matter injuries and persistent post-concussive symptoms (PPCS). We hypothesized that athletes with PPCS would have neurocognitive impairments and white matter abnormalities that could be revealed by advanced neuroimaging using ultra-high field strength diffusion tensor (DTI) and diffusion kurtosis (DKI) imaging metrics and cerebrospinal fluid (CSF) biomarkers. A cohort of athletes with PPCS severity limiting the ability to work/study and participate in sport school and/or social activities for ≥6 months completed 7T magnetic resonance imaging (MRI) (morphological T1-weighed volumetry, DTI and DKI), extensive neuropsychological testing, symptom rating, and CSF biomarker sampling. Twenty-two athletes with PPCS and 22 controls were included. Concussed athletes performed below norms and significantly lower than controls on all but one of the psychometric neuropsychology tests. Supratentorial white and gray matter, as well as hippocampal volumes did not differ between concussed athletes and controls. However, of the 72 examined white matter tracts, 16% of DTI and 35% of DKI metrics (in total 28%) were significantly different between concussed athletes and controls. DKI fractional anisotropy and axial kurtosis were increased, and DKI radial diffusivity and radial kurtosis decreased in concussed athletes when compared with controls. CSF neurofilament light (NfL; an axonal injury marker), although not glial fibrillary acidic protein, correlated with several diffusion metrics. In this first 7T DTI and DKI study investigating PPCS, widespread microstructural alterations were observed in the white matter, correlating with CSF markers of axonal injury. More white matter changes were observed using DKI than using DTI. These white matter alterations may indicate persistent pathophysiological processes following concussion in sport.
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