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

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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; Raghupathi, Ramesh; Scherbel, Uwe; Wieloch, Tadeusz; McIntosh, Tracy K.

In: Journal of Neuroscience Research, Vol. 88, No. 15, 2010, p. 3414-3423.

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T1 - Deletion of the p53 tumor suppressor gene improves neuromotor function but does not attenuate regional neuronal cell loss following experimental brain trauma in mice.

AU - Tomasevic, Gregor

AU - Raghupathi, Ramesh

AU - Scherbel, Uwe

AU - Wieloch, Tadeusz

AU - McIntosh, Tracy K

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Laboratory for Experimental Brain Research (013041000), Neurosurgery (013026000)

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

U2 - 10.1002/jnr.22491

DO - 10.1002/jnr.22491

M3 - Article

VL - 88

SP - 3414

EP - 3423

JO - Journal of Neuroscience Research

T2 - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 1097-4547

IS - 15

ER -