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Critical Care Medicine:
doi: 10.1097/01.ccm.0000439198.39093.83
Oral Abstract Session: Brain Injury, Repair, and Recovery: PDF Only

13: AUTOPHAGY BIOMARKERS BECLIN 1 AND P62 ARE DETECTABLE IN CEREBROSPINAL FLUID AFTER TBI IN CHILDREN.

Au, Alicia; Aneja, Raj; Bell, Michael; Feldman, Keri; Kochanek, Patrick; Clark, Robert

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Abstract

Introduction: Autophagy is an efficient process by which damaged proteins and organelles are recycled. It is known to be upregulated after traumatic brain injury (TBI); however the role of autophagy (benefit vs. harm) has yet to be determined. Beclin 1 and p62 are essential components for the formation of autophagosomes. Beclin 1 is a Bcl-2 interacting protein with early involvement in the nucleation phase of phagopore formation, while p62 functions further downstream, consumed during the elongation phase through its interaction with the autophagosomal microtubule-associated protein light chain 3 (LC3). Methods: Twenty-five children admitted to the Pediatric Intensive Care Unit after severe TBI had CSF collected from existing external ventricular devices on day 1, 3 and 7. Lumbar CSF from 6 patients without TBI or meningoencephalitis served as controls. Beclin 1 and p62 levels were measured by enzyme-linked immunosorbent assay. Data are presented as mean +/- SEM unless otherwise noted. Results: CSF Beclin 1 levels was increased after TBI, peaking at day 3 (control: 0.14 +/- 0.04 ng/ml, day 1: 0.25 +/- 0.04, day 3: 0.46 +/- 0.1, and day 7: 0.32 +/- 0.04). Peak CSF Beclin 1 was inversely correlated with abusive head trauma (AHT; rs=0.429, P=0.04; Spearman). p62 CSF levels were detectable in CSF of 10 children. Overall, CSF p62 levels were increased compared to controls (control: 0 +/- 0 ng/ml, day 1: 0.08 +/- 0.05, day 3: 0.176 +/- 0.12, day 7: 0.27 +/- 0.15). Peak CSF p62 was associated with poor outcome (unfavorable Glasgow Outcome Scale (GOS)) after controlling for age and Glasgow Coma Scale score (P=0.038, Multiple Logistic Regression). Conclusions: Both Beclin 1 and p62 are increased in CSF after pediatric TBI. Increased Beclin 1 levels positively correlate with accidental TBI, but were negatively correlated with AHT, implying differences in autophagic flux in these two subsets of TBI patients. Elevated p62 levels are associated with unfavorable GOS, consistent with decreased autophagy or reduced turnover of autophagosomes, particularly in a subset of patients with poor outcome after TBI. However, these results must be interpreted with caution as p62 was only detectable in a small subset of patients. Further study is required to determine the role of autophagy after TBI.(C) 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins
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