Human neuronal apoptosis secondary to traumatic brain injury and the regulative role of apoptosis-related genes.
OBJECTIVE
To observe human neuronal apoptosis secondary to traumatic brain injury, and to elucidate its regulative mechanism and the change of expression of apoptosis-related genes.


METHODS
Specimens of brain were collected from cases of traumatic brain injury in humans. The histological and cellular morphology was examined by light and electron microscopy. The extent of DNA injury to cortical neurons was detected by using TUNEL. By in situ hybridisation and immunohistochemistry the mRNA changes and protein expression of Bcl-2, Bax, p53, and caspase 3 p20 subunit were observed.


RESULTS
Apoptotic neurons appeared following traumatic brain injury, peaked at 24 hours and lasted for 7 days. In normal brain tissue activated caspase 3 was rare, but a short time after trauma it became activated. The activity peaked at 20-28 hours and remained higher than normal for 5-7 days. There was no expression of Bcl-2 mRNA and Bcl-2 protein in normal brain tissue but 8 hours after injury their expression became evident and then increased, peaked at 2-3 days and remained higher than normal for 5-7 days. The primary expression of Bax-mRNA and Bax protein was high in normal brain tissue. At 20-28 hours they increased and remained high for 2-3 days; on the 7th days they returned to a normal level. In normal brain tissue, p53mRNA and P53 were minimally expressed. Increased expression was detected at the 8th hour, and decreased at 20-28 hours but still remained higher than normal on the 5th day.


CONCLUSIONS
Following traumatic injury to the human brain, apoptotic neurons appear around the focus of trauma. The mRNA and protein expression of Bcl-2, Bax and p53 and the activity of caspase 3 enzyme are increased.
Yang
Shu-Yuan
SY
Department of Neurosurgery, Tianjin Medical University, General Hospital, Tianjin 300052, China. dhcan@public.tpt.tj.cn
Xue
Liang
L
D000328:Adult; D001930:Brain Injuries / Q000473:pathology* / Q000503:physiopathology; D053179:Caspase 7; D020169:Caspases / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D009336:Necrosis; D009474:Neurons / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; 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; C505520:CASP7 protein, human; D053179:Caspase 7; D020169:Caspases