Dynamics of synaptic damage in severe traumatic brain injury revealed by cerebrospinal fluid SNAP-25 and VILIP-1

BackgroundBiomarkers of neuronal, glial cells and inflammation in traumatic brain injury (TBI) are available but they do not specifically reflect the damage to synapses, which represent the bulk volume of the brain. Experimental models have demonstrated extensive involvement of synapses in acute TBI...

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Published in:	Journal of neurology, neurosurgery and psychiatry Vol. 95; no. 12; pp. 1158 - 1167
Main Authors:	olde Heuvel, Florian, Li, Zhenghui, Riedel, Daniel, Halbgebauer, Steffen, Oeckl, Patrick, Mayer, Benjamin, Gotzman, Nina, Shultz, Sandy, Semple, Bridgette, Tumani, Hayrettin, Ludolph, Albert C, Boeckers, Tobias Maria, Morganti-Kossmann, Cristina, Otto, Markus, Roselli, Francesco
Format:	Journal Article
Language:	English
Published:	England BMJ Publishing Group Ltd 02-06-2024 BMJ Publishing Group LTD
Subjects:	Antibodies Biomarkers Cerebrospinal fluid Cytokines Glasgow Coma Scale Neurosurgery Proteins Software Traumatic brain injury United States > US traumatic brain injury
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Summary:	BackgroundBiomarkers of neuronal, glial cells and inflammation in traumatic brain injury (TBI) are available but they do not specifically reflect the damage to synapses, which represent the bulk volume of the brain. Experimental models have demonstrated extensive involvement of synapses in acute TBI, but biomarkers of synaptic damage in human patients have not been explored.MethodsSingle-molecule array assays were used to measure synaptosomal-associated protein-25 (SNAP-25) and visinin-like protein 1 (VILIP-1) (along with neurofilament light chain (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), glial fibrillar acidic protein (GFAP), interleukin-6 (IL-6) and interleukin-8 (IL-8)) in ventricular cerebrospinal fluid (CSF) samples longitudinally acquired during the intensive care unit (ICU) stay of 42 patients with severe TBI or 22 uninjured controls.ResultsCSF levels of SNAP-25 and VILIP-1 are strongly elevated early after severe TBI and decline in the first few days. SNAP-25 and VILIP-1 correlate with inflammatory markers at two distinct timepoints (around D1 and then again at D5) in follow-up. SNAP-25 and VILIP-1 on the day-of-injury have better sensitivity and specificity for unfavourable outcome at 6 months than NFL, UCH-L1 or GFAP. Later elevation of SNAP-25 was associated with poorer outcome.ConclusionSynaptic damage markers are acutely elevated in severe TBI and predict long-term outcomes, as well as, or better than, markers of neuroaxonal injury. Synaptic damage correlates with initial injury and with a later phase of secondary inflammatory injury.
Bibliography:	Original research ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-3050 1468-330X 1468-330X
DOI:	10.1136/jnnp-2024-333413