TY  - JOUR
AU  - Olde Heuvel, Florian
AU  - Li, Zhenghui
AU  - Riedel, Daniel
AU  - Halbgebauer, Steffen
AU  - Oeckl, Patrick
AU  - Mayer, Benjamin
AU  - Gotzman, Nina
AU  - Shultz, Sandy
AU  - Semple, Bridgette
AU  - Tumani, Hayrettin
AU  - Ludolph, Albert C
AU  - Böckers, Tobias
AU  - Morganti-Kossmann, Cristina
AU  - Otto, Markus
AU  - Roselli, Francesco
TI  - Dynamics of synaptic damage in severe traumatic brain injury revealed by cerebrospinal fluid SNAP-25 and VILIP-1.
JO  - Journal of neurology, neurosurgery, and psychiatry
VL  - 95
IS  - 12
SN  - 0022-3050
CY  - London
PB  - BMJ Publishing Group
M1  - DZNE-2024-01360
SP  - 1158 - 1167
PY  - 2024
AB  - 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.
KW  - Humans
KW  - Brain Injuries, Traumatic: cerebrospinal fluid
KW  - Synaptosomal-Associated Protein 25: cerebrospinal fluid
KW  - Male
KW  - Adult
KW  - Female
KW  - Biomarkers: cerebrospinal fluid
KW  - Middle Aged
KW  - Neurocalcin: cerebrospinal fluid
KW  - Synapses: pathology
KW  - Neurofilament Proteins: cerebrospinal fluid
KW  - Ubiquitin Thiolesterase: cerebrospinal fluid
KW  - Glial Fibrillary Acidic Protein: cerebrospinal fluid
KW  - Interleukin-6: cerebrospinal fluid
KW  - Young Adult
KW  - Aged
KW  - traumatic brain injury (Other)
KW  - Synaptosomal-Associated Protein 25 (NLM Chemicals)
KW  - Biomarkers (NLM Chemicals)
KW  - Neurocalcin (NLM Chemicals)
KW  - neurofilament protein L (NLM Chemicals)
KW  - VSNL1 protein, human (NLM Chemicals)
KW  - Neurofilament Proteins (NLM Chemicals)
KW  - SNAP25 protein, human (NLM Chemicals)
KW  - Ubiquitin Thiolesterase (NLM Chemicals)
KW  - Glial Fibrillary Acidic Protein (NLM Chemicals)
KW  - Interleukin-6 (NLM Chemicals)
KW  - UCHL1 protein, human (NLM Chemicals)
KW  - GFAP protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC11671962
C6  - pmid:38825349
DO  - DOI:10.1136/jnnp-2024-333413
UR  - https://pub.dzne.de/record/272981
ER  -