- January 14, 2026
- David J. Sharp, et al., Imperial College London
Topic/Product:
Inflammation Panel 250
Disease Area:
Traumatic Brain Injury (TBI)
Sample Type:
Plasma
Abstract
Traumatic Brain Injury (TBI) triggers an acute systemic inflammatory response, which may contribute to poor long-term outcomes. Additionally, pre-existing factors associated with increased inflammation, such as age, may interact with this acute post-TBI inflammation to influence outcomes. Previous investigations of post-TBI inflammation have typically assessed small numbers of cytokines, but novel high-dimensional proteomic approaches can sensitively detect a broad range of inflammatory markers and more fully characterise post-TBI inflammation.
We analysed plasma from 84 participants in the BIO-AX-TBI cohort [n=37 acute, moderate– severe TBI (Mayo Criteria), n=22 acute non-TBI trauma (NTT), n=28 non-injured controls (CON)] on the Alamar NULISA™ Inflammation panel, assessing >200 inflammatory markers. The NTT group allowed differentiation of TBI-specific from general injury-related acute inflammatory responses. Inflammatory markers were correlated with plasma levels of NFL (neurofilament light), GFAP, total tau, UCH-L1 (all Simoa®) and S100B (Millipore); and subacute (10 days to 6 weeks post-injury) 3T MRI measures of lesion volume and white matter injury (fractional anisotropy).
Differential expression analysis identified 4 markers showing TBI-specific elevations in plasma levels (VSNL1, IL1RN/IL-1Ra, GFAP, IKBKG), whilst derangements in other inflammatory markers likely reflected a non-specific injury response. Higher VSNL1 levels were associated with greater lesion volume (rs=0.53), and higher IL1RN/IL-1Ra levels were associated with more white matter injury (rs=-0.66, both FDR-adjusted p<0.05).
The non-specific injury response was associated with functional outcome at 6-months – higher IL33 levels in those with good (Glasgow Outcome Scale-Extended, GOS-E, 5-8) versus poor (GOS-E 1-4) outcomes (W=47, FDR-corrected p=0.0024). To assess age-related effects, we calculated “inflammation age” by applying an Elastic Net model trained on a public healthy control dataset. The “age gap” (“inflammation age” minus calendar age) was greater in TBI than CON, and also greater in young participants.
In summary, the acute post-TBI inflammatory response is comprised of both TBI-specific and non-specific injury components. These inflammatory responses are associated with structural brain injury measures and overall functional outcome. We additionally find that age influences the acute inflammatory response. Our study highlights VSNL1, IL1RN/IL-1Ra and IL33 as potential inflammatory mediators of post-TBI pathophysiology.
Authors & Affiliations
Lucia M. Li¹²*, Eleftheria Kodosaki³⁴, Chloe Xu¹, Amanda Heslegrave³⁴, Henrik Zetterberg³⁴⁵⁶⁷⁸⁹¹⁰, Neil Graham¹², Karl Zimmerman¹², Elena Garbero¹¹, Federico Moro¹², Sandra Magnoni¹³, Guido Bertolini¹¹, David J. Loane¹⁴¹⁵, and David J. Sharp¹²
¹ Department of Brain Sciences, Imperial College London, Sir Michael Uren Building, 86 Wood Lane, London W12 0BZ, UK
² UK Dementia Research Institute Centre for Care Research & Technology, London, UK
³ Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK
⁴ Dementia Research Institute at UCL, London, UK
⁵ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
⁶ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
⁷ Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
⁸ Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin–Madison, Madison, WI 53792, USA
⁹ Hong Kong Center for Neurodegenerative Diseases, InnoHK, Hong Kong, China
¹⁰ Centre for Brain Research, Indian Institute of Science, Bangalore, India
¹¹ Department of Medical Epidemiology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy
¹² Department of Acute Brain and Cardiovascular Injury, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
¹³ Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy
¹⁴ School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland
¹⁵ Department of Anesthesiology and Shock, Trauma and Anesthesiology (STAR) Research Center, University of Maryland School of Medicine, Baltimore, MD, USA