title: Stress worsens endothelial function and ischemic stroke via glucocorticoids.
abstract: OBJECTIVE
  Chronic stress is associated with increased stroke risk. However, the underlying pathophysiological mechanisms are poorly understood. We examined the effects of chronic stress on endothelial function and ischemic brain injury in a mouse model.
  
  
  METHODS
  129/SV mice were treated with glucocorticoid receptor antagonist mifepristone (25 mg kg(-1)/d) or vehicle and exposed to 28 days of chronic stress consisting of exposure to rat, restraint stress, and tail suspension. Heart rate and blood pressure were continuously recorded by telemetry. Endothelial nitric oxide synthase mRNA and protein expression as well as superoxide production and lipid hydroperoxides were quantified. Endothelium-dependent vasorelaxation was measured in aortic rings. Ischemic lesion volume was quantified after 30 minutes filamentous middle cerebral artery occlusion and 72 hours reperfusion.
  
  
  RESULTS
  Chronic stress caused a significant increase in heart rate, impaired endothelium-dependent vasorelaxation, increased superoxide production, and reduced aortic and brain endothelial nitric oxide synthase levels. Animals exposed to chronic stress showed major increases in ischemic lesion size. These deleterious effects of stress were completely reversed by treatment with mifepristone.
  
  
  CONCLUSIONS
  Chronic stress increases stroke vulnerability likely through endothelial dysfunction, which can be reversed by a glucocorticoid receptor antagonist.
authors.affiliation: Klinik für Neurologie, Charité-Universitätsmedizin Berlin, Chariteplatz 1, Berlin, Germany 10117.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Balkaya
authors.forename: Vincent
authors.initials: V
authors.lastname: Prinz
authors.forename: Florian
authors.initials: F
authors.lastname: Custodis
authors.forename: Karen
authors.initials: K
authors.lastname: Gertz
authors.forename: Golo
authors.initials: G
authors.lastname: Kronenberg
authors.forename: Jan
authors.initials: J
authors.lastname: Kroeber
authors.forename: Klaus
authors.initials: K
authors.lastname: Fink
authors.forename: Ralph
authors.initials: R
authors.lastname: Plehm
authors.forename: Peter
authors.initials: P
authors.lastname: Gass
authors.forename: Ulrich
authors.initials: U
authors.lastname: Laufs
authors.forename: Matthias
authors.initials: M
authors.lastname: Endres
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005938:Glucocorticoids / Q000502:physiology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D011897:Random Allocation; D051381:Rats; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology; D020521:Stroke / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D013481:Superoxides / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D013481:Superoxides