title: Disruption of Bax protein prevents neuronal cell death but produces cognitive impairment in mice following traumatic brain injury.
abstract: Apoptosis contributes to delayed neuronal cell death in traumatic brain injury (TBI). To investigate if Bax plays a role in neuronal cell death and functional outcome after TBI, Bax gene disrupted (null) mice and wild-type (WT) controls were subjected to the controlled cortical impact (CCI) model of TBI. Motor function in WT and Bax null mice was evaluated using the round beam balance and the wire grip test on days 0-5. Spatial memory was assessed using a Morris Water Maze adopted for mice on days 14-18 post-injury. For histopathological analysis, animals were sacrificed 24 h and 21 days post-injury. In all three behavioral tests, the sham and TBI-injured Bax null mice performed significantly worse than their WT sham and TBI-injured counterparts. However, Bax null mice exhibited a higher percentage of surviving neurons in the CA1 and CA3 regions of hippocampus measured at 21 days post-injury. At 24 h after trauma, Bax null mice had fewer TUNEL positive cells in the CA1 and dentate regions of hippocampus as compared to WT mice, suggesting that deletion of the Bax gene ameliorates hippocampal cell death after TBI. Sham-operated Bax null mice had significantly greater brain volume as compared to WT mice. Thus, it is possible that Bax deficiency in the transgenic mice produces developmental behavioral effects, perhaps due to Bax's role in regulating cell death during development.
authors.affiliation: Geriatric Research Educational and Clinical Center, Veterans Administration Pittsburgh Healthcare System, Pittsburgh, Pennsylvania 15206, USA.
authors.forename: Roya
authors.initials: R
authors.lastname: Tehranian
authors.forename: Marie E
authors.initials: ME
authors.lastname: Rose
authors.forename: Vincent
authors.initials: V
authors.lastname: Vagni
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Pickrell
authors.forename: Raymond P
authors.initials: RP
authors.lastname: Griffith
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Robert S B
authors.initials: RS
authors.lastname: Clark
authors.forename: C Edward
authors.initials: CE
authors.lastname: Dixon
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
authors.forename: Steven H
authors.initials: SH
authors.lastname: Graham
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D016923:Cell Death / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D003072:Cognition Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009069:Movement Disorders / Q000209:etiology / Q000503:physiopathology; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D009460:Neurologic Examination; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000235:genetics*
chemical_list: D051017:Apoptosis Regulatory Proteins; D051028:bcl-2-Associated X Protein