Cerebral apoptosis in severe traumatic brain injury patients: an in vitro, in vivo, and postmortem study.
One of the most important recent observations in traumatic brain injury (TBI) relates to the potential role of apoptosis in secondary brain injury. We aimed to analyze the presence of apoptosis and the expression of apoptosis-related proteins in brain samples from patients with TBI. We also tried to find any association between the in situ results and the in vitro observations in a neuronal model of induced-apoptosis. Brain tissue from the pericontusional zone (PCZ) of patients with traumatic contusions and from post-mortem samples was analyzed. Immunohistochemical analyses of apoptosis-related proteins and the terminal deoxynucleotide transferase-mediated nick end labeling (TUNEL) method to determine the presence of apoptotic cells were performed. Apoptotic rates on neuronal cells induced by jugular bulb vein sera was determined by flow cytometry. TUNEL-positive cells were detected in all PCZ of traumatic contusions and in most of PCZ in post-mortem specimens (none in control; p = 0.026). In vivo samples showed higher expression of antiapoptotic proteins Bcl-2 (p = 0.027) and Bcl-XL (p = 0.014) than post-mortem samples. In autopsies, the expression of Fas and Bim (p < 0.05) were higher in PCZ than in the zone distal from the contusion. In vitro studies showed that apoptotic rate was an independent factor associated with mortality at 6 months (p = 0.014). In the receiving operator curve (ROC) curve, a cut-off point of 66.5% showed a sensitivity of 89.5% and specificity of 66.7% in the prediction of patients' death. Cerebral apoptosis is a prominent form of cell death in the PCZ of human traumatic cerebral contusions, and high rates of in vitro apoptosis are associated with a poorer prognosis after TBI.
Miñambres
Eduardo
E
Service of Intensive Care, Hospital Universitario Marqués de Valdecilla, Avenida Marqués de Valdecilla s/n, Santander, Spain.
Ballesteros
Maria Angeles
MA
Mayorga
Marta
M
Marin
Maria José
MJ
Muñoz
Pedro
P
Figols
Javier
J
López-Hoyos
Marcos
M
D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000032:analysis / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D016716:PC12 Cells; D011180:Postmortem Changes; D011237:Predictive Value of Tests; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012372:ROC Curve; D051381:Rats; D019014:fas Receptor / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606778:Bcl2l11 protein, rat; D015415:Biomarkers; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019014:fas Receptor