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

• Published in: The Journal of pediatrics Vol. 137; no. 2; pp. 197 - 204
• Main Authors: Clark, Robert S.B., Kochanek, Patrick M., Adelson, P.David, Bell, Michael J., Carcillo, Joseph A., Chen, Minzhi, Wisniewski, Stephen R., Janesko, Keri, Whalen, Michael J., Graham, Steven H.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01-08-2000; Elsevier
• Subjects: Adolescent; Age Factors; Analysis of Variance; Apoptosis; Biological and medical sciences; 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; Injuries of the nervous system and the skull. Diseases due to physical agents; Linear Models; Male; Medical sciences; Multivariate Analysis; Nucleosomes - metabolism; Pennsylvania - epidemiology; Proto-Oncogene Proteins c-bcl-2 - cerebrospinal fluid; Survival Analysis; Temporal Lobe - metabolism; Traumas. Diseases due to physical agents; Pennsylvania; PCD; TBI; TUNEL; CSF; ELISA; Human; Nervous system diseases; Pathophysiology; Craniocerebral; Diseases of the osteoarticular system; Infant; Cerebrospinal fluid; Trauma; Protein; Cerebral disorder; Cell death; Central nervous system disease; Adolescent; Skull disease; Child
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1067/mpd.2000.106903

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. (J Pediatr 2000;137:197-204)