Original Article

Neurocritical Care

, Volume 12, Issue 3, pp 337-341

First online:

Detectable Levels of Cytochrome c and Activated Caspase-9 in Cerebrospinal Fluid after Human Traumatic Brain Injury

  • Ribal S. DarwishAffiliated withDepartment of Anesthesiology, Critical Care Medicine Division, University of Maryland Medical Center Email author 
  • , Nana S. AmiridzeAffiliated withDepartment of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine

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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.


Nine adult patients with severe TBI (GCS ≤ 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.


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).


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.


Activated caspase-9 Cytochrome c Traumatic brain injury