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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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.

Detaljer

Författare
  • Gregor Tomasevic
  • Ramesh Raghupathi
  • Uwe Scherbel
  • Tadeusz Wieloch
  • Tracy K McIntosh
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurovetenskaper
Originalspråkengelska
Sidor (från-till)3414-3423
TidskriftJournal of Neuroscience Research
Volym88
Utgivningsnummer15
StatusPublished - 2010
PublikationskategoriForskning
Peer review utfördJa