Evaluation of apoptosis in cerebrospinal fluid of patients with severe head injury.
OBJECTIVE
To determine whether sFas, caspase-3, proteins which propagate apoptosis, and bcl-2, a protein which inhibits apoptosis, would be increased in cerebrospinal fluid (CSF) in patients with severe traumatic brain injury (TBI) and to examine the correlation of sFas, caspase-3, and bcl-2 with each other and with clinical variables.


METHODS
sFas, caspase-3, and bcl-2 were measured in CSF of 14 patients with severe TBI on days 1, 2, 3, 5, 7, and 10 post-trauma. The results were compared with CSF samples from control patients who had no brain and spinal pathology and had undergone spinal anesthesia for some other reason. Soluble Fas and bcl-2 were measured by ELISA while caspase-3 was measured enzymatically.


RESULTS
No sFas, caspase-3, and bcl-2 activities were found in CSF of controls, but activities significantly increased in CSF of patients at all time points post-trauma (p < 0.01). Caspase-3 significantly correlated to intracranial pressure (p = 0.01) and cerebral perfusion pressure (p = 0.04). Soluble Fas and caspase-3 peaks coincided on day 5 post-trauma and there was significant association between sFas and caspase-3 increase (p = 0.01).


CONCLUSIONS
This study indicates a prolonged activation of pro-apoptotic (sFas, caspase-3) and anti-apoptotic (bcl-2) proteins after severe TBI in humans. The degree of activation of particularly caspase-3 may be related to the severity of the injury. Parallel increases of these three molecules may indicate a pivotal role of apoptosis in the pathophysiology of post-traumatic brain oedema, secondary cell destruction and chronic cell loss following severe TBI and may open new targets for post-traumatic therapeutic interventions.
Uzan
M
M
Department of Neurosurgery, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey. uzan@istanbul
Erman
H
H
Tanriverdi
T
T
Sanus
G Z
GZ
Kafadar
A
A
Uzun
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000032:analysis / Q000134:cerebrospinal fluid; D001930:Brain Injuries / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000503:physiopathology; D053148:Caspase 3 / Q000134:cerebrospinal fluid; D002648:Child; D002675:Child, Preschool; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008297:Male; D009410:Nerve Degeneration / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000503:physiopathology; D011237:Predictive Value of Tests; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000134:cerebrospinal fluid; D015854:Up-Regulation; D019014:fas Receptor / Q000134:cerebrospinal fluid
D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D053148:Caspase 3