title: Inhibition of mitochondrial p53 abolishes the detrimental effects of social isolation on ischemic brain injury.
abstract: OBJECTIVE
  Social isolation (SI) increases stroke incidence and delays poststroke recovery. Women may be at greater risk from the negative consequences of SI, but few studies have examined both sexes in experimental models, and none have evaluated the effects of isolation initiated after stroke. The effects of poststroke SI in men and women were examined, and the role of mitochondrial P53 was evaluated.
  
  
  METHODS
  C57Bl6 mice were pair-housed (PH; male and ovariectomized female) for 2 weeks, subjected to stroke and then assigned to a housing condition (isolated or PH). The effects of housing on infarct volume and recovery were examined. Changes in Bcl-2 and mitochondrial p53 were assessed by Western blot. A mitochondrial p53 inhibitor (pifithrin-μ) was given to mice of both sexes.
  
  
  RESULTS
  Compared with pair-housed mice, poststroke SI significantly increased infarct size in both sexes; SI mice also had worse neurological deficits. The detrimental effects of SI paralleled increases in mitochondrial p53 levels. Pharmacological inhibition of mitochondrial p53 using pifithrin-μ abolished the detrimental effects of SI and reduced cell death.
  
  
  CONCLUSIONS
  Poststroke SI results in increased ischemic injury in both sexes. The effect of housing on infarct was more pronounced in women. Targeting the mitochondrial P53 pathway could minimize the detrimental effects of isolation after stroke.
authors.affiliation: From the Departments of Neuroscience (V.R.V., R.V., L.M.O'K., Y.X., J.C., B.F., L.D.M.) and Neurology (L.D.M.), University of Connecticut, Farmington.
authors.forename: Venugopal Reddy
authors.initials: VR
authors.lastname: Venna
authors.affiliation: From the Departments of Neuroscience (V.R.V., R.V., L.M.O'K., Y.X., J.C., B.F., L.D.M.) and Neurology (L.D.M.), University of Connecticut, Farmington.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Verma
authors.affiliation: From the Departments of Neuroscience (V.R.V., R.V., L.M.O'K., Y.X., J.C., B.F., L.D.M.) and Neurology (L.D.M.), University of Connecticut, Farmington.
authors.forename: Lena M
authors.initials: LM
authors.lastname: O'Keefe
authors.affiliation: From the Departments of Neuroscience (V.R.V., R.V., L.M.O'K., Y.X., J.C., B.F., L.D.M.) and Neurology (L.D.M.), University of Connecticut, Farmington.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: From the Departments of Neuroscience (V.R.V., R.V., L.M.O'K., Y.X., J.C., B.F., L.D.M.) and Neurology (L.D.M.), University of Connecticut, Farmington.
authors.forename: Joshua
authors.initials: J
authors.lastname: Crapser
authors.affiliation: From the Departments of Neuroscience (V.R.V., R.V., L.M.O'K., Y.X., J.C., B.F., L.D.M.) and Neurology (L.D.M.), University of Connecticut, Farmington.
authors.forename: Brett
authors.initials: B
authors.lastname: Friedler
authors.affiliation: From the Departments of Neuroscience (V.R.V., R.V., L.M.O'K., Y.X., J.C., B.F., L.D.M.) and Neurology (L.D.M.), University of Connecticut, Farmington.
authors.forename: Louise D
authors.initials: LD
authors.lastname: McCullough
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism* / Q000523:psychology; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D012934:Social Isolation; D020521:Stroke / Q000150:complications; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53
keywords: apoptosis; ischemia; reperfusion injury; sex-specific; stroke