Transgenic mice that overexpress the anti-apoptotic Bcl-2 protein have improved histological outcome but unchanged behavioral outcome after traumatic brain injury.
Increasing evidence suggests that apoptosis is a contributing factor to neuronal cell death in traumatic brain injury (TBI). There is increased expression, cleavage and activation of caspases as well as other proteins known to regulate apoptosis in neurons after TBI. These proteins include the proto-oncogene Bcl-2 which belongs to a family of proteins with both pro- and anti-apoptotic properties. To investigate the role of apoptosis in TBI and the importance of Bcl-2 protein on the severity and outcome of injury, Bcl-2 overexpressing transgenic and wild-type control mice were subjected to the controlled cortical impact model of TBI. There was no significant difference in the cleavage of caspase-3 or caspase-9 detected by Western blotting of hippocampal samples from transgenic or wild-type mice after TBI. Bcl-2 transgenic mice had smaller contusion volumes and increased numbers of surviving neurons in CA2 but not other regions of hippocampus compared to wild-type controls. By contrast, there was no difference in motor function determined by the round beam balance and wire grip tests between transgenic and wild-type mice after TBI. Cognitive function assessed by the Morris water maze was also not different between groups. These results suggest that overexpression of Bcl-2 is only partially neuroprotective and other members of this protein family may prove to be more important in protecting neurons from cell death.
Tehranian
Roya
R
Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare Center, and Department of Neurology, University of Pittsburgh, PA 15261, USA.
Rose
Marie E
ME
Vagni
Vincent
V
Griffith
R P
RP
Wu
Shasha
S
Maits
Sara
S
Zhang
Xiaopeng
X
Clark
Robert S B
RS
Dixon
C Edward
CE
Kochanek
Patrick M
PM
Bernard
Ora
O
Graham
Steven H
SH
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D015153:Blotting, Western / Q000379:methods; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016923:Cell Death / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D020287:In Situ Nick-End Labeling / Q000379:methods; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D011597:Psychomotor Performance / Q000502:physiology; D011930:Reaction Time / Q000235:genetics; D013997:Time Factors
D019253:Proto-Oncogene Proteins c-bcl-2