Home > Publications Database > Dynamics of synaptic damage in severe traumatic brain injury revealed by cerebrospinal fluid SNAP-25 and VILIP-1. |
Journal Article | DZNE-2024-01360 |
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2024
BMJ Publishing Group
London
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Please use a persistent id in citations: doi:10.1136/jnnp-2024-333413
Abstract: Biomarkers 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.Single-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.CSF 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.Synaptic 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.
Keyword(s): Humans (MeSH) ; Brain Injuries, Traumatic: cerebrospinal fluid (MeSH) ; Synaptosomal-Associated Protein 25: cerebrospinal fluid (MeSH) ; Male (MeSH) ; Adult (MeSH) ; Female (MeSH) ; Biomarkers: cerebrospinal fluid (MeSH) ; Middle Aged (MeSH) ; Neurocalcin: cerebrospinal fluid (MeSH) ; Synapses: pathology (MeSH) ; Neurofilament Proteins: cerebrospinal fluid (MeSH) ; Ubiquitin Thiolesterase: cerebrospinal fluid (MeSH) ; Glial Fibrillary Acidic Protein: cerebrospinal fluid (MeSH) ; Interleukin-6: cerebrospinal fluid (MeSH) ; Young Adult (MeSH) ; Aged (MeSH) ; traumatic brain injury ; Synaptosomal-Associated Protein 25 ; Biomarkers ; Neurocalcin ; neurofilament protein L ; VSNL1 protein, human ; Neurofilament Proteins ; SNAP25 protein, human ; Ubiquitin Thiolesterase ; Glial Fibrillary Acidic Protein ; Interleukin-6 ; UCHL1 protein, human ; GFAP protein, human
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