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Activity based proteome profiling of serum serine hydrolases: application in pediatric abusive head trauma
  • +5
  • Estelle Maret,
  • Kim Wiskott,
  • Tobias Shipley,
  • Federica Gilardi,
  • Marc Augsburger,
  • Aurelien Thomas,
  • Tony Fracasso,
  • Tatjana Sajic
Estelle Maret
University Center of Legal Medicine Lausanne-Geneva
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Kim Wiskott
University Center of Legal Medicine Lausanne-Geneva
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Tobias Shipley
CURML - CHUV
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Federica Gilardi
University Center of Legal Medicine Lausanne-Geneva
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Marc Augsburger
CURM Unit of Forensic Toxicology and Chemistry
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Aurelien Thomas
University Center of Legal Medicine Lausanne-Geneva
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Tony Fracasso
CURML - CHUV
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Tatjana Sajic
University Center of Legal Medicine Lausanne-Geneva

Corresponding Author:[email protected]

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Abstract

Purpose: Traumatic brain injury (TBI), including pediatric abusive head trauma (AHT), is the leading cause of death and disability in children and young adults worldwide. The current understanding of trauma-induced molecular changes in the brain of human subjects with intracranial haemorrhage (ICH) remains inadequate and requires further investigation to improve the outcome and management of TBI in the clinic. Calcium-mediated damage at the site of brain injury has been shown to activate several catalytic enzymes. Experimental design: Serine hydrolases (SHs) are major catalytic enzymes involved in the biochemical pathways of blood coagulation, systemic inflammation and neuronal signaling. Here we investigated activity-based protein profiling (ABPP) by measuring the activity status of SH enzymes in the serum of infants with severe ICH as a consequence of AHT or atraumatic infants who died of sudden infant death syndrome (SIDS). Results: Our proof-of-principle study revealed significantly reduced physiological activity of dozens of metabolic SHs in the serum of infants with severe AHT compared to the SIDS group, with some of the enzymes being related to neurodevelopment and basic brain metabolism.
Submitted to Clinical Applications
09 Apr 2024Reviewer(s) Assigned
23 Apr 2024Review(s) Completed, Editorial Evaluation Pending
23 Apr 2024Editorial Decision: Revise Major