Overexpression of Bcl-2 is neuroprotective after experimental brain injury in transgenic mice.
The cell death regulatory protein, Bcl-2, has been suggested to participate in the pathophysiology of various neurological disorders, including traumatic brain injury (TBI). The cognitive function and histopathologic sequelae after controlled cortical impact brain injury were evaluated in transgenic (TG) mice that overexpress human Bcl-2 protein (n = 13) and their wild type (WT) controls (n = 9). Although brain-injured Bcl-2 TG mice exhibited similar posttraumatic deficits in a Morris water maze (MWM) test of spatial memory as their WT counterparts at 1 week postinjury, the preinjury learning ability of Bcl-2 TG mice was impaired significantly compared with their WT littermates (P < 0.05). In contrast, histopathologic analysis revealed significantly attenuated tissue loss in the ipsilateral hemisphere (p < 0.01) and decreased tissue loss in ipsilateral hippocampal area CA3 (P < 0.001) and the dentate gyrus (P < 0.01) in brain-injured Bcl-2 TG mice compared with brain-injured WT mice. Immunohistochemical evaluation of glial fibrillary acidic protein also revealed a significant decrease in reactive astrocytosis in the ipsilateral dorsal thalamus (P < 0.05) and the ventral thalamus (P < 0.01) in brain-injured Bcl-2 TG mice. These results suggest that overexpression of Bcl-2 protein may play a protective role in neuropathologic sequelae after TBI.
Nakamura
M
M
Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Raghupathi
R
R
Merry
D E
DE
Scherbel
U
U
Saatman
K E
KE
Mcintosh
T K
TK
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000502:physiology; D002540:Cerebral Cortex / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D003072:Cognition Disorders / Q000503:physiopathology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D019254:Genes, bcl-2; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006624:Hippocampus / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000378:metabolism*
D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents