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 proce
ss of apoptosis. We sought to determine whether there was evidence of cellu
lar apoptosis in clinically collected materials from human head trauma pati
ents, as well as to attempt to determine the pathway by which it may occur.
METHODS: Thirty-one sequential specimens of brain tissue excised during eme
rgency craniotomy for evacuation of cerebral contusions with mass effect we
re examined. Non-necrotic pericontusional tissues were detected in 11 sampl
es. These were examined for the presence of apoptotic cells by the terminal
deoxynucleotide transferase-mediated nick end labeling method as well as b
y immunohistochemistry to detect possible expression of the apoptosis-relat
ed genes p53, bcl-2, and bax.
RESULTS: Bar expression was detected in all patients, whereas bcl-2 express
ion was noted in six patients, Terminal deoxynucleotide transferase-mediate
d nick end labeling-positive cells were noted in eight patients. One instan
ce of p53-positive immunostaining was observed. Patients with bcl-2 express
ion had a better survival rate than patients in whom no bcl-2 expression wa
s noted (P = 0.01).
CONCLUSION: Although necrosis seemed to be the main finding in cerebral con
tusions, these results support the hypothesis that apoptosis does occur in
patients after traumatic brain injury, and this may contribute to the secon
dary 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 bar
inhibitors to prevent apoptosis.