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Deletion of the p53 tumor suppressor gene improves neuromotor function but does not attenuate regional neuronal cell loss following experimental brain trauma in mice.

Tomasevic, Gregor LU ; Raghupathi, Ramesh; Scherbel, Uwe; Wieloch, Tadeusz LU and McIntosh, Tracy K (2010) In Journal of Neuroscience Research 88(15). p.3414-3423
Abstract
Deletion of the tumor suppressor gene p53 has been shown to improve the outcome in experimental models of focal cerebral ischemia and kainate-induced seizures. To evaluate the potential role of p53 in traumatic brain injury, genetically modified mice lacking a functional p53 gene (p53(-/-), n = 9) and their wild-type littermates (p53(+/+), n = 9) were anesthetized and subjected to controlled cortical impact (CCI) experimental brain trauma. After brain injury, neuromotor function was assessed by using composite neuroscore and rotarod tests. By 7 days posttrauma, p53(-/-) mice exhibited significantly improved neuromotor function, in the composite neuroscore (P = 0.002) as well as in two of three individual tests, when compared with... (More)
Deletion of the tumor suppressor gene p53 has been shown to improve the outcome in experimental models of focal cerebral ischemia and kainate-induced seizures. To evaluate the potential role of p53 in traumatic brain injury, genetically modified mice lacking a functional p53 gene (p53(-/-), n = 9) and their wild-type littermates (p53(+/+), n = 9) were anesthetized and subjected to controlled cortical impact (CCI) experimental brain trauma. After brain injury, neuromotor function was assessed by using composite neuroscore and rotarod tests. By 7 days posttrauma, p53(-/-) mice exhibited significantly improved neuromotor function, in the composite neuroscore (P = 0.002) as well as in two of three individual tests, when compared with brain-injured p53(+/+) animals. CCI resulted in the formation of a cortical cavity (mean volume = 6.1 mm(3)) 7 days postinjury in p53(+/+) as well as p53(-/-) mice. No difference in lesion volume was detected between the two genotypes (P = 0.95). Although significant cell loss was detected in the ipsilateral hippocampus and thalamus of brain-injured animals, no differences between p53(+/+) and p53(-/-) mice were detected. Although our results suggest that lack of the p53 gene results in augmented recovery of neuromotor function following experimental brain trauma, they do not support a role for p53 acting as a mediator of neuronal death in this context, underscoring the complexity of its role in the injured brain. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Neuroscience Research
volume
88
issue
15
pages
3414 - 3423
publisher
John Wiley & Sons
external identifiers
  • WOS:000283609900019
  • PMID:20890990
  • Scopus:78649396818
ISSN
1097-4547
DOI
10.1002/jnr.22491
language
English
LU publication?
yes
id
cd7378ed-be0e-4f8e-a79c-6918cf01572c (old id 1711426)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20890990?dopt=Abstract
date added to LUP
2010-11-05 12:14:34
date last changed
2016-10-13 04:28:17
@misc{cd7378ed-be0e-4f8e-a79c-6918cf01572c,
  abstract     = {Deletion of the tumor suppressor gene p53 has been shown to improve the outcome in experimental models of focal cerebral ischemia and kainate-induced seizures. To evaluate the potential role of p53 in traumatic brain injury, genetically modified mice lacking a functional p53 gene (p53(-/-), n = 9) and their wild-type littermates (p53(+/+), n = 9) were anesthetized and subjected to controlled cortical impact (CCI) experimental brain trauma. After brain injury, neuromotor function was assessed by using composite neuroscore and rotarod tests. By 7 days posttrauma, p53(-/-) mice exhibited significantly improved neuromotor function, in the composite neuroscore (P = 0.002) as well as in two of three individual tests, when compared with brain-injured p53(+/+) animals. CCI resulted in the formation of a cortical cavity (mean volume = 6.1 mm(3)) 7 days postinjury in p53(+/+) as well as p53(-/-) mice. No difference in lesion volume was detected between the two genotypes (P = 0.95). Although significant cell loss was detected in the ipsilateral hippocampus and thalamus of brain-injured animals, no differences between p53(+/+) and p53(-/-) mice were detected. Although our results suggest that lack of the p53 gene results in augmented recovery of neuromotor function following experimental brain trauma, they do not support a role for p53 acting as a mediator of neuronal death in this context, underscoring the complexity of its role in the injured brain.},
  author       = {Tomasevic, Gregor and Raghupathi, Ramesh and Scherbel, Uwe and Wieloch, Tadeusz and McIntosh, Tracy K},
  issn         = {1097-4547},
  language     = {eng},
  number       = {15},
  pages        = {3414--3423},
  publisher    = {ARRAY(0x880f9a8)},
  series       = {Journal of Neuroscience Research},
  title        = {Deletion of the p53 tumor suppressor gene improves neuromotor function but does not attenuate regional neuronal cell loss following experimental brain trauma in mice.},
  url          = {http://dx.doi.org/10.1002/jnr.22491},
  volume       = {88},
  year         = {2010},
}