title: Six-month ischemic mice show sensorimotor and cognitive deficits associated with brain atrophy and axonal disorganization.
abstract: OBJECTIVE
  To identify long-term sensorimotor and cognitive deficits and to evaluate structural alterations in brain ischemic mice.
  
  
  METHODS
  C57Bl/6J male mice were subjected to 30 min transient middle cerebral artery occlusion (tMCAo) or sham surgery. Sensorimotor deficits, exploratory behavior, and cognitive functions were evaluated up to 6 months. Cortical and subcortical damage were analyzed by MRI multiparameter analysis and histopathology.
  
  
  RESULTS
  tMCAo mice showed significant sensorimotor deficits in the rotarod, negative geotaxis, neuroscore, and beam walk tests. They also showed impairment in exploratory behavior in the open field test and in spatial learning in the Morris water maze. T2-weighted MRI revealed a volume reduction in injured brain areas at 12 and 24 weeks postinjury. Brain atrophy was shown by MRI and conventional postmortem analysis. Diffusion tensor imaging on the external capsule showed increased values of axial and radial diffusivity. Fiber tracking revealed a reduction in the number and length of ipsilateral fibers.
  
  
  CONCLUSIONS
  tMCAo in mice induces sensorimotor and cognitive impairments detectable at least up to 6 months postinjury, associated with brain atrophy, and axonal and myelin damage of the external capsule. These behavioral tests and anatomical investigations may represent important tools in translational studies in cerebral ischemia.
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Department of Neuroscience, Milan, Italy.
authors.forename: Elisa R
authors.initials: ER
authors.lastname: Zanier
authors.forename: Francesca
authors.initials: F
authors.lastname: Pischiutta
authors.forename: Pia
authors.initials: P
authors.lastname: Villa
authors.forename: Alessandra
authors.initials: A
authors.lastname: Paladini
authors.forename: Mery
authors.initials: M
authors.lastname: Montinaro
authors.forename: Edoardo
authors.initials: E
authors.lastname: Micotti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Orrù
authors.forename: Luigi
authors.initials: L
authors.lastname: Cervo
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: De Simoni
mesh_terms: D000818:Animals; D001284:Atrophy; D001369:Axons / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000150:complications* / Q000473:pathology / Q000523:psychology; D003072:Cognition Disorders / Q000209:etiology*; D005106:Exploratory Behavior; D020244:Infarction, Middle Cerebral Artery; D008279:Magnetic Resonance Imaging; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D011597:Psychomotor Performance
keywords: Behavior; Brain damage; Brain ischemia; Diffusion tensor imaging; Mice