title: The behavioural effect of middle cerebral artery occlusion on apolipoprotein-E deficient mice.
abstract: The behavioural effects of middle cerebral artery occlusion (MCAO) in apolipoprotein-E deficient (Apo-E KO) mice were investigated using a modified SHIRPA protocol and compared with effects in wild type littermate controls. The MCA was permanently occluded by insertion of an intraluminal filament to its origin on the Circle of Willis and behavioural responses were observed 24 h later. MCAO treatment caused a range of changes in the wild type mice whereas, few differences were observed in the Apo-E KO mice in the behavioural observation. In the rotarod task, MCAO operated wild type mice showed a significant reduction in performance compared with sham-operated and non-operated animals. In contrast, both sham and MCAO operated Apo-E KO mice showed significant impairment compared with non-operated controls. A significant reduction in performance was also observed in sham-operated Apo-E KO compared with sham-operated wild type mice. In locomotor activity tests, no significant reduction in activity was observed between non-operated and sham-operated wild type controls, whereas a significant reduction was found between sham operated and MCAO operated mice. In the Apo-E KO mice, both sham and MCAO-operated animals showed a reduction in locomotor activity compared with non-operated mice. Furthermore, Apo-E KO MCAO mice showed a worsened deficit in locomotor activity, which was significantly correlated with exacerbated cortical lesion volume, unlike wild-type MCAO mice. This study shows that Apo-E KO animals demonstrate an impaired functional recovery post surgery which may be further compounded by post experimental stroke and also demonstrates the utility of the SHIRPA test system for investigating behavioural changes in functional outcome post stroke.
authors.affiliation: Neurology CEDD, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Essex CM19 5AW, Harlow, UK. jon_hatcher-1@gsk.com
authors.forename: J P
authors.initials: JP
authors.lastname: Hatcher
authors.forename: D
authors.initials: D
authors.lastname: Virley
authors.forename: S J
authors.initials: SJ
authors.lastname: Hadingham
authors.forename: J
authors.initials: J
authors.lastname: Roberts
authors.forename: A J
authors.initials: AJ
authors.lastname: Hunter
authors.forename: A A
authors.initials: AA
authors.lastname: Parsons
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics*; D001522:Behavior, Animal / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D010641:Phenotype; D004856:Postural Balance / Q000502:physiology
chemical_list: D001057:Apolipoproteins E