Apoptosis occurs after cerebral contusions in humans.
OBJECTIVE
Animal model systems have shown that head trauma can induce cell death in regions of the brain away from the site of the impact via a process of apoptosis. We sought to determine whether there was evidence of cellular apoptosis in clinically collected materials from human head trauma patients, as well as to attempt to determine the pathway by which it may occur.


METHODS
Thirty-one sequential specimens of brain tissue excised during emergency craniotomy for evacuation of cerebral contusions with mass effect were examined. Non-necrotic pericontusional tissues were detected in 11 samples. These were examined for the presence of apoptotic cells by the terminal deoxynucleotide transferase-mediated nick end labeling method as well as by immunohistochemistry to detect possible expression of the apoptosis-related genes p53, bcl-2, and bax.


RESULTS
Bax expression was detected in all patients, whereas bcl-2 expression was noted in six patients. Terminal deoxynucleotide transferase-mediated nick end labeling-positive cells were noted in eight patients. One instance of p53-positive immunostaining was observed. Patients with bcl-2 expression had a better survival rate than patients in whom no bcl-2 expression was noted (P = 0.01).


CONCLUSIONS
Although necrosis seemed to be the main finding in cerebral contusions, these results support the hypothesis that apoptosis does occur in patients after traumatic brain injury, and this may contribute to the secondary injury processes that are seen with head injury. Patients in whom anti-apoptotic bcl-2 is induced seem to have a better prognosis. This may have important clinical significance in the development of bcl-2 homologs or bax inhibitors to prevent apoptosis.
Ng
I
I
Department of Neurosurgery, Tan Tock Seng Hospital, Singapore, Republic of Singapore.
Yeo
T T
TT
Tang
W Y
WY
Soong
R
R
Ng
P Y
PY
Smith
D R
DR
D000328:Adult; D000368:Aged; D017209:Apoptosis; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D015331:Cohort Studies; D003399:Craniotomy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein