Cytochrome c, a biomarker of apoptosis, is increased in cerebrospinal fluid from infants with inflicted brain injury from child abuse.
Previous studies suggest that delayed neuronal death occurs in patients with inflicted traumatic brain injury (TBI) from child abuse. It is unknown whether the mode of this delayed neuronal death represents apoptosis or necrosis, a distinction that carries therapeutic ramifications. Cytochrome c, an electron transport chain component, can be released from mitochondria under conditions of cellular stress, whereupon it can initiate and serve as a biomarker of apoptosis. To resolve this issue, cytochrome c concentration was determined in 167 ventricular cerebrospinal fluid (CSF) samples from 67 infants and children with TBI (including 15 patients diagnosed with child abuse) by ELISA. Controls included lumbar CSF from 19 infants and children without trauma or meningitis. A multivariate model adjusted for multiple within-subject observations was used to identify clinical variables associated with CSF cytochrome c. Other apoptosis-related proteins were also examined in a subset of TBI patients. Increased CSF cytochrome c was independently associated with inflicted TBI (P=0.0001) and female gender (P=0.04), but not age, Glasgow coma scale score, or survival. Other apoptosis-related proteins including Fas and caspase-1 were increased in CSF after TBI, but did not independently discriminate between accidental and inflicted TBI. These data suggest that apoptosis, as detected by the presence of cytochrome c in CSF, is uniquely prominent among the subset of TBI patients diagnosed with child abuse. The degree of apoptosis after TBI also appears to be gender-dependent. Development of strategies targeting apoptosis after TBI, particularly in victims of child abuse and in girls, appears justified.
Satchell
Margaret A
MA
Department of Critical Care Medicine, The Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Lai
Yichen
Y
Kochanek
Patrick M
PM
Wisniewski
Stephen R
SR
Fink
Ericka L
EL
Siedberg
Neal A
NA
Berger
Rachel P
RP
DeKosky
Steven T
ST
Adelson
P David
PD
Clark
Robert S B
RS
D017209:Apoptosis; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology*; D020170:Caspase 1 / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000737:chemistry / Q000378:metabolism*; D002648:Child; D002649:Child Abuse; D002675:Child, Preschool; D045304:Cytochromes c / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male
D015415:Biomarkers; D045304:Cytochromes c; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1