Detectable levels of cytochrome C and activated caspase-9 in cerebrospinal fluid after human traumatic brain injury.
BACKGROUND
The intrinsic pathway of apoptosis has been proposed as one mechanism of cell death after traumatic brain injury (TBI). This study tested the hypothesis that cytochrome c and activated caspase-9 are released into the cerebrospinal fluid (CSF) after severe TBI and that their presence correlates with mitochondrial injury and severity of neurologic outcome.


METHODS
Nine adult patients with severe TBI (GCS < or = 8) underwent placement of intraventricular catheters for monitoring and management of intracranial pressure. CSF was sampled at catheter insertion (2-26 h after injury) and at intervals of 24, 48, and 72 h thereafter. Control samples were obtained from patients undergoing spinal anesthesia (ASA1). CSF levels of cytochrome c and activated caspase-9 were measured using ELISA.


RESULTS
Cytochrome c was detected in 18 (51.4%) samples, in the range of 0.08-5 ng/ml; mean value for cytochrome c was 0.44 ng/ml (SD +/- 0.632). Activated caspase-9 was detected in 10 samples (28.6%); mean value was 0.28 ng/ml (SD +/- 0.39). R (s) between cytochrome c and Glasgow outcome score (GOS) was -0.25 (P = 0.14), and between GOS and activated caspase-9 was -0.35 (P = 0.04). R calculated based on linear regression of activated caspase-9 and cytochrome c concentrations was 0.18. Control CSF samples had no detectable levels of either marker (detection level for cytochrome c was 0.08 ng/ml and 0.20 for activated caspase-9).


CONCLUSIONS
We concluded that activated caspase-9 and cytochrome c are present in the CSF of patients with severe TBI. Activated caspase-9 shows weak correlation with poor neurologic outcome.
Darwish
Ribal S
RS
Department of Anesthesiology, Critical Care Medicine Division, University of Maryland Medical Center, 22 S. Greene Street, Baltimore, MD 21201-1595, USA. Rdarwish@anes.umm.edu
Amiridze
Nana S
NS
D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000201:enzymology* / Q000473:pathology; D053453:Caspase 9 / Q000134:cerebrospinal fluid*; D045304:Cytochromes c / Q000134:cerebrospinal fluid*; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D023261:Glasgow Outcome Scale; D006801:Humans; D007427:Intracranial Pressure / Q000502:physiology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000502:physiology; D011379:Prognosis; D012016:Reference Values; D055815:Young Adult
D015415:Biomarkers; D045304:Cytochromes c; D053453:Caspase 9