title: Cerebral hemodynamic reserve and vascular remodeling in C57/BL6 mice are influenced by age.
abstract: OBJECTIVE
  Age is the most important risk factor for ischemic stroke. Recent experiments evidenced an age-associated rarefaction of the native collateral vasculature. The purpose of this study was to assess in what way age and arteriogenesis influence cortical perfusion and recovery of hemodynamic impairment in aged and young C57/BL6 mice.
  
  
  METHODS
  After model establishment of chronic cerebral hypoperfusion in the C57/BL6 strain, sustained hemodynamic impairment was induced by permanent unilateral internal carotid artery occlusion in animals aged 4 to 6 weeks, 12 weeks, and 18 months. Functional and morphological outcome was assessed by laser speckle imaging before and during acetazolamide challenge on Days 0, 3, 7, and 14 and latex/carbon black angiography and immunohistochemistry on Day 21.
  
  
  RESULTS
  Although internal carotid artery occlusion did not result in a reduction of baseline perfusion, it led to significant hemodynamic impairment in all age groups. Furthermore, baseline perfusion in sham and cerebrovascular reactivity after internal carotid artery occlusion were significantly lower in animals aged 18 months (468±57 Flux; 20.8%±17%) compared with mice aged 4 to 6 weeks (568±120 Flux; 30.3%±17%) and 12 weeks (591±72 Flux; 34.2%±12%) from the beginning until Day 7 of the monitoring period. Functional outcome was in line with a 27% reduction of native leptomeningeal anastomoses in aged mice and only limited collateral outgrowth compared with young animals. Strikingly, all age groups reached spontaneous functional compensation by Day 14.
  
  
  CONCLUSIONS
  Next to limited collateral remodeling, our results suggest that a hampered cerebrovascular response with age could intensify the risk for hemodynamic stroke in the elderly.
authors.affiliation: Department of Neurosurgery, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Hecht
authors.forename: Jin
authors.initials: J
authors.lastname: He
authors.forename: Irina
authors.initials: I
authors.lastname: Kremenetskaia
authors.forename: Melina
authors.initials: M
authors.lastname: Nieminen
authors.forename: Peter
authors.initials: P
authors.lastname: Vajkoczy
authors.forename: Johannes
authors.initials: J
authors.lastname: Woitzik
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000473:pathology* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003097:Collateral Circulation / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020521:Stroke / Q000209:etiology / Q000473:pathology / Q000503:physiopathology