title: Autophagy Biomarkers Beclin 1 and p62 are Increased in Cerebrospinal Fluid after Traumatic Brain Injury.
abstract: BACKGROUND
  Autophagy is a process that recycles damaged proteins and organelles. Beclin 1 is involved in the nucleation phase, while p62 is consumed during the elongation phase. We hypothesized that these autophagy biomarkers are increased in cerebrospinal fluid (CSF) after traumatic brain injury (TBI) in children and associated with unfavorable outcome.
  
  
  METHODS
  Thirty children with severe TBI had CSF collected on days 1, 3, and 7. Patients without TBI or meningoencephalitis served as controls. Beclin 1 and p62 were measured by ELISA. Outcome was assigned 6 months after injury (Glasgow Outcome Scale score; GOS).
  
  
  RESULTS
  Mean and peak CSF beclin 1 and p62 levels were increased compared to controls (P < 0.05). Peak p62 levels were higher in patients with unfavorable versus favorable outcome (0.79 ± 1.03 vs. 0.17 ± 0.54 ng/ml, respectively; mean ± SD, P = 0.002) and were independently associated with outcome when controlling for age and initial Glasgow Coma Scale score (P = 0.019; AUC 0.88, 95% CI 0.76, 1.00).
  
  
  CONCLUSIONS
  Beclin 1 and p62 are increased in CSF after TBI, suggesting increased autophagy with impairment of, and/or exceeding the capacity for, autophagic flux. The association of increased p62 with unfavorable outcome suggests that autophagy in excess of the capacity to clear degradation products may be deleterious after TBI.
authors.affiliation: Department of Critical Care Medicine, Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh Medical Center, 4401 Penn Avenue, Faculty Pavilion, Suite 2000, Pittsburgh, PA, 15224, USA. auak@upmc.edu.|Department of Pediatrics, Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. auak@upmc.edu.
authors.forename: Alicia K
authors.initials: AK
authors.lastname: Au
authors.affiliation: Department of Critical Care Medicine, Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh Medical Center, 4401 Penn Avenue, Faculty Pavilion, Suite 2000, Pittsburgh, PA, 15224, USA.|Department of Pediatrics, Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Rajesh K
authors.initials: RK
authors.lastname: Aneja
authors.affiliation: Department of Critical Care Medicine, Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh Medical Center, 4401 Penn Avenue, Faculty Pavilion, Suite 2000, Pittsburgh, PA, 15224, USA.|Department of Pediatrics, Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Hülya
authors.initials: H
authors.lastname: Bayır
authors.affiliation: Department of Critical Care Medicine, Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh Medical Center, 4401 Penn Avenue, Faculty Pavilion, Suite 2000, Pittsburgh, PA, 15224, USA.|Department of Pediatrics, Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.|Department of Neurological Surgery, Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bell
authors.affiliation: Department of Critical Care Medicine, Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh Medical Center, 4401 Penn Avenue, Faculty Pavilion, Suite 2000, Pittsburgh, PA, 15224, USA.
authors.forename: Keri
authors.initials: K
authors.lastname: Janesko-Feldman
authors.affiliation: Department of Critical Care Medicine, Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh Medical Center, 4401 Penn Avenue, Faculty Pavilion, Suite 2000, Pittsburgh, PA, 15224, USA.|Department of Pediatrics, Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
authors.affiliation: Department of Critical Care Medicine, Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh Medical Center, 4401 Penn Avenue, Faculty Pavilion, Suite 2000, Pittsburgh, PA, 15224, USA.|Department of Pediatrics, Safar Center for Resuscitation Research and the Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Robert S B
authors.initials: RSB
authors.lastname: Clark
mesh_terms: D000293:Adolescent; D001343:Autophagy; D000071186:Beclin-1 / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D000070642:Brain Injuries, Traumatic / Q000134:cerebrospinal fluid*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D017063:Outcome Assessment, Health Care; D016601:RNA-Binding Proteins / Q000134:cerebrospinal fluid*; D012720:Severity of Illness Index
chemical_list: C491997:BECN1 protein, human; D000071186:Beclin-1; D015415:Biomarkers; C118585:P62 protein, human; D016601:RNA-Binding Proteins
keywords: Autophagic flux; Autophagy; Biomarkers; Cerebrospinal fluid; Outcome; Pediatrics; Traumatic brain injury