Traumatic brain injury in mice deficient in Bid: effects on histopathology and functional outcome.
Bid is a proapoptotic member of the Bcl-2 family that mediates cell death by caspase-dependent and -independent pathways. We tested mice genetically deficient in Bid in a controlled cortical impact (CCI) model to examine the hypothesis that Bid contributes to cell death and functional outcome after traumatic brain injury. After CCI, truncated Bid (15 kDa) was robustly detected in cortical brain homogenates of wild-type mice. Bid-/- mice had decreased numbers of cortical cells with acute plasmalemma injury at 6 h (wild type (WT), 1721+/-124; Bid-/-, 1173+/-129 cells/ x 200 field; P<0.01), decreased numbers of cells expressing cleaved caspase-3 in the dentate gyrus at 48 h (WT, 113+/-15; Bid-/-, 65+/-9 cells/ x 200 field; P<0.05), and reduced lesion volume at 12 days (Bid-/-, 5.9+/-0.4 mm(3); WT, 8.4+/-0.4 mm(3); P<0.001), but did not differ from WT mice at later times after injury regarding lesion size (30 days) or brain tissue atrophy (40 days). Compared with naïve mice, injured mice in both groups performed significantly worse on motor and Morris water maze (MWM) tests; however, mice deficient in Bid did not differ from WT in postinjury motor and MWM performance. The data show that Bid deficiency decreases early posttraumatic brain cell death and tissue damage, but does not reduce functional outcome deficits after CCI in mice.
Bermpohl
Daniela
D
Neuroscience Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
You
Zerong
Z
Korsmeyer
Stanley J
SJ
Moskowitz
Michael A
MA
Whalen
Michael J
MJ
D000818:Animals; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics / Q000378:metabolism*; D001522:Behavior, Animal; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D051023:BH3 Interacting Domain Death Agonist Protein; C494815:Bid protein, mouse; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases