Abstract 12
Category: Basic Science
At the end of the session, participants will be able to:
- Understand the need for serum biomarkers of neurological injury in critically ill patients
- Understand the role that neuropathology plays in the validation of potential biomarkers of brain injury
COI Disclosure:
I have a relationship with a for-profit and/or a not-for-profit organization to disclose.
Name of for-profit or not-for-profit organization(s) : CIHR; ASC
Description of relationship(s) : I receive funding from CIHR and the Alzheimer Society of Canada
Presenter
Dr. Veronica Hirsch-Reinshagen
Chloe P. Allen1, Catie N. Futhey2, Aditya Swaro3, Jordan D. Bird1, Sophie Stukas4, Mark S. Cembrowski3,4,5,6, Cheryl L. Wellington4,5,8, Mypinder S. Sekhon1,4,8, Veronica Hirsch‐Reinshagen7,8
1Division of Critical Care Medicine, Department of Medicine, Vancouver General Hospital and University of British Columbia, Vancouver, BC, Canada;
2MD/PhD Program, University of British Columbia, Vancouver, BC, Canada;
3Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada;
4Djavad Mowafaghian Centre for Brain Health, Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada;
5School of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada; 6Department of Mathematics, University of British Columbia, Vancouver, BC, Canada;
7Division of Neuropathology, Department of Pathology and Laboratory Medicine, Vancouver General Hospital and University of British Columbia, Vancouver, BC, Canada;
8International Collaborations on Repair Discoveries, University of British Columbia, Vancouver, BC, Canada.
Target Audience:
Pathologists, Residents, Medical Students
CanMEDS:
Medical Expert (the integrating role), Communicator, Collaborator, Scholar
Neuropathological correlates of serum biomarkers during the dying process in humans
Abstract
Neurocritical patients (NCPs) admitted to the intensive care unit (ICU) have severe neurological damage stemming from diverse causes including hypoxic ischemic brain injury (HIBI), intracranial hemorrhage (ICH), and traumatic brain injury (TBI), among others. Recently, blood-based neurologic biomarkers have emerged as a promising tool for prognostication, however, their utility for the diagnosis of tissue injury severity and the insights they provide into the pathophysiology of this brain injury are limited. We aimed to investigate the relationship of 120 blood-based systemic and neurologic biomarkers prior to the withdrawal of life-sustaining therapies (WLST) in humans with pre-mortem clinical measures and post-mortem neuropathological features in different neurocritical conditions. Clinical and demographic data, along with arterial biospecimens, were obtained from twenty-nine patients immediately prior to WLSM with subsequent post-mortem neuropathological evaluation. Proteomic analysis of plasma samples was performed using the ARGO HT platform. A standard neuropathological evaluation was performed followed by exploratory and advanced data analyses. Ten brain-enhanced markers were identified that exhibited significant positive associations with neuropathological features, most prominently selective neuronal death (SND) and reactive gliosis: ENO2, MAPT, NEFH, NEFL, NRGN, pTau-217, SNAP25, SNCB, and UCHL1. Notably, these associations were also successful in striating patients by their respective cause of injury. No significant correlations were present with chronic vascular, neurodegenerative, or inflammatory neuropathology. Collectively, these results provide neuropathological demonstration of the brain tissue changes in neurocritically-ill patients and their immediate correlation with serum biomarkers. They also demonstrate that select brain-enhanced biomarkers likely possess diagnostic and prognostic utility.