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Overexpression of Bcl‐2 is neuroprotective after experimental brain injury in transgenic mice
Journal article   Peer reviewed

Overexpression of Bcl‐2 is neuroprotective after experimental brain injury in transgenic mice

Michio Nakamura, Ramesh Raghupathi, Diane E Merry, Uwe Scherbel, Kathryn E Saatman and Tracy K Mcintosh
Journal of comparative neurology (1911), v 412(4), pp 681-692
04 Oct 1999
PMID: 10464363

Abstract

cognitive function Morris water maze hippocampus neuroprotection protooncogene Apoptosis
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. J. Comp. Neurol. 412:681–692, 1999. © 1999 Wiley‐Liss, Inc.

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