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


METHODS
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.
Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Pittsburgh, PA 15213, USA.
R S
RS
Clark
P M
PM
Kochanek
P D
PD
Adelson
M J
MJ
Bell
J A
JA
Carcillo
M
M
Chen
S R
SR
Wisniewski
K
K
Janesko
M J
MJ
Whalen
S H
SH
Graham
D000293:Adolescent; D000367:Age Factors; D000704:Analysis of Variance; D017209:Apoptosis; D001930:Brain Injuries / Q000134:cerebrospinal fluid / Q000209:etiology / Q000401:mortality / Q000503:physiopathology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D015600:Glasgow Coma Scale; D006801:Humans; D007223:Infant; D016014:Linear Models; D008297:Male; D015999:Multivariate Analysis; D009707:Nucleosomes / Q000378:metabolism; D010414:Pennsylvania / Q000453:epidemiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000134:cerebrospinal fluid*; D016019:Survival Analysis; D013702:Temporal Lobe / Q000378:metabolism
D009707:Nucleosomes; D019253:Proto-Oncogene Proteins c-bcl-2