title: BCL-2 overexpression attenuates cortical cell loss after traumatic brain injury in transgenic mice.
abstract: The proto-oncogene, BCL-2, has been suggested to participate in cell survival during development of, and after injury to, the CNS. Transgenic (TG) mice overexpressing human Bcl-2 (n = 21) and their wild-type (WT) littermates (n = 18) were subjected to lateral controlled cortical impact brain injury. Lateral controlled cortical impact brain injury resulted in the formation of a contusion in the injured cortex at 2 days, which developed into a well-defined cavity by 7 days in both WT and TG mice. At 7 days after injury, brain-injured TG mice had a significantly reduced cortical lesion (volume = 1.99 mm3) compared with that of the injured WT mice (volume = 5.1 mm3, P < 0.01). In contrast, overexpression of BCL-2 did not affect the extent of hippocampal cell death after lateral controlled cortical impact brain injury. Analysis of motor function revealed that both brain-injured WT and TG mice exhibited significant right-sided deficits at 2 and 7 days after injury (P < 0.05 compared with the uninjured controls). Although composite neuroscores (sum of scores from forelimb and hind limb flexion, lateral pulsion, and inclined plane tests) were not different between WT and TG brain-injured mice, TG mice had a slightly but significantly reduced deficit in the inclined plane test (P < 0.05 compared to the WT mice). These data suggest that the cell death regulatory gene, BCL-2, may play a protective role in the pathophysiology of traumatic brain injury.
authors.affiliation: Department of Neurosurgery, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: R
authors.initials: R
authors.lastname: Raghupathi
authors.forename: S C
authors.initials: SC
authors.lastname: Fernandez
authors.forename: H
authors.initials: H
authors.lastname: Murai
authors.forename: S P
authors.initials: SP
authors.lastname: Trusko
authors.forename: R W
authors.initials: RW
authors.lastname: Scott
authors.forename: W K
authors.initials: WK
authors.lastname: Nishioka
authors.forename: T K
authors.initials: TK
authors.lastname: McIntosh
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology*; D019254:Genes, bcl-2; D006429:Hemiplegia / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007438:Introns; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity; D009928:Organ Specificity; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000096:biosynthesis; D015183:Restriction Mapping; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins