Influence of apoptosis on neurological outcome following traumatic cerebral contusion

Abstract

Object. Apoptosis has increasingly been implicated in the pathobiology of traumatic brain injury (TBI). The present study was undertaken to confirm the presence of apoptosis in the periischemic zone (PIZ) of traumatic cerebral contusions and to determine the role of apoptosis, if any, in neurological outcome. Methods. Brain tissue harvested at Wentworth Hospital from the PIZ in 29 patients with traumatic supratentorial contusions was compared with brain tissue resected in patients with epilepsy. Immunohistochemical analyses were performed on the tissues to see if they contained the apoptosis-related proteins p53, bcl-2, bax, and caspase-3. The findings were then correlated to demographic, clinical, surgical, neuroimaging, and outcome data. In the PIZ significant increases of bax (18-fold; p < 0.005) and caspase-3 (20-fold; p < 0.005) were recorded, whereas bcl-2 was upregulated in only 14 patients (48.3%; 2.9-fold increase) compared with control tissue. Patients in the bcl-2—positive group exhibited improved outcomes at the 18-month follow-up examination despite an older mean age and lower mean admission Glasgow Coma Scale score (p < 0.03). Caspase-3 immunostaining was increased in those patients who died (Glasgow Outcome Scale [GOS] Score 1, 12 patients) when compared with those who experienced a good outcome (GOS Score 4 or 5, 17 patients) (p < 0.005). Regression analysis identified bcl-2—negative status (p < 0.04, odds ratio [OR] 5.5; 95% confidence interval [CI] 1.1–28.4) and caspase-3—positive status (p < 0.01, OR 1.4, 95% CI 1.1—1.8) as independent predictors of poor outcome. No immunostaining for p53 was recorded in the TBI specimens. Conclusions. The present findings confirm apoptosis in the PIZ of traumatic cerebral contusions and indicate that this form of cell death can influence neurological outcome following a TBI.