Increases in bcl-2 protein in cerebrospinal fluid and evidence for programmed cell death in infants and children after severe traumatic brain injury

J Pediatr. 2000 Aug;137(2):197-204. doi: 10.1067/mpd.2000.106903.

Abstract

Objectives: To determine whether bcl-2, a protein that inhibits apoptosis, would be increased in cerebrospinal fluid (CSF) in infants and children after traumatic brain injury (TBI) and to examine the association of bcl-2 concentration with clinical variables.

Study design: Bcl-2 was measured in CSF from 23 children (aged 2 months-16 years) with severe TBI and from 19 children without TBI or meningitis (control subjects) by enzyme-linked immunosorbent assay. CSF oligonucleosome concentration was also determined as a marker of DNA degradation. Brain samples from 2 patients undergoing emergent decompressive craniectomies were analyzed for bcl-2 with Western blot and for DNA fragmentation with TUNEL (terminal deoxynucleotidyl-transferase mediated biotin-dUTP nick-end labeling).

Results: CSF bcl-2 concentrations were increased in patients with TBI versus control subjects (P =.01). Bcl-2 was increased in patients with TBI who survived versus those who died (P =.02). CSF oligonucleosome concentration tended to be increased after TBI (P =.07) and was not associated with bcl-2. Brain tissue samples showed an increase in bcl-2 in patients with TBI versus adult brain bank control samples and evidence of DNA fragmentation within cells with apoptotic morphology.

Conclusions: Bcl-2 may participate in the regulation of cell death after TBI in infants and children. The increase in bcl-2 seen in patients who survived is consistent with a protective role for this anti-apoptotic protein after TBI.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Age Factors
  • Analysis of Variance
  • Apoptosis*
  • Brain Injuries / cerebrospinal fluid
  • Brain Injuries / etiology
  • Brain Injuries / mortality
  • Brain Injuries / physiopathology*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Glasgow Coma Scale
  • Humans
  • Infant
  • Linear Models
  • Male
  • Multivariate Analysis
  • Nucleosomes / metabolism
  • Pennsylvania / epidemiology
  • Proto-Oncogene Proteins c-bcl-2 / cerebrospinal fluid*
  • Survival Analysis
  • Temporal Lobe / metabolism

Substances

  • Nucleosomes
  • Proto-Oncogene Proteins c-bcl-2