TY - JOUR
T1 - Overexpression of Bcl-2 is neuroprotective after experimental brain injury in transgenic mice
AU - Nakamura, Michio
AU - Raghupathi, Ramesh
AU - Merry, Diane E.
AU - Scherbel, Uwe
AU - Saatman, Kathryn E.
AU - McIntosh, Tracy K.
PY - 1999/10/4
Y1 - 1999/10/4
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Cognitive function
KW - Hippocampus
KW - Morris water maze
KW - Neuroprotection
KW - Protooncogene
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U2 - 10.1002/(SICI)1096-9861(19991004)412:4<681::AID-CNE9>3.0.CO;2-F
DO - 10.1002/(SICI)1096-9861(19991004)412:4<681::AID-CNE9>3.0.CO;2-F
M3 - Article
C2 - 10464363
AN - SCOPUS:0033523589
SN - 0021-9967
VL - 412
SP - 681
EP - 692
JO - Journal of Comparative Neurology
JF - Journal of Comparative Neurology
IS - 4
ER -