title: Longitudinal assessment of infarct progression, brain metabolism and behavior following anterior cerebral artery occlusion in rats.
abstract: BACKGROUND
  Stroke patients suffering from occlusion of the anterior cerebral artery (ACAo) develop cognitive and executive deficits. Experimental models to investigate such functional impairments and recovery are rare and not satisfyingly validated.
  
  
  METHODS
  We stereotactically injected the vasoconstrictor endothelin-1 (ET-1) close to the ACA of rats and assessed magnitude and course of CBF reduction using [(14)C]iodoantipyrine autoradiography and [(15)O]H2O-PET. [(18)F]FDG-PET and T2-weighted MRI determined regional metabolic and structural alterations. To test cognitive and executive functions, we analyzed decision-making in a food-carrying task, spatial working memory in a spontaneous alternation task and anxiety in an elevated plus maze test before and 1 month after ACAo.
  
  
  RESULTS
  CBF decreased immediately after ET-1 injection, started to recover 1-2h and returned to control 4h thereafter. Metabolic and structural lesions developed permanently in the ACA territory. Hypometabolism occurring bilaterally in the piriform region may reflect diaschisis. Behavioral testing after ACAo revealed context-dependent changes in decision making, exploratory activity and walking speed, as well as decreased anxiety and spatial working memory.
  
  
  CONCLUSIONS
  Aside from modeling a known entity of stroke patients, ACAo in rats allows to longitudinally study deterioration of cognitive and executive function without major interference by disturbed primary motor function. It complements therefore stroke research since common models using middle cerebral artery occlusion (MCAo) all affect motor function severely.
  
  
  CONCLUSIONS
  The established ACAo model in rats effectively reflects deficits characteristic for ACA stroke in humans. It is furthermore highly suitable for longitudinal assessment of cognitive and executive functions.
authors.affiliation: Max Planck Institute for Neurological Research, Gleueler Str. 50, 50931 Koeln, Germany. Electronic address: heike.endepols@uk-koeln.de.
authors.forename: Heike
authors.initials: H
authors.lastname: Endepols
authors.affiliation: Max Planck Institute for Neurological Research, Gleueler Str. 50, 50931 Koeln, Germany.
authors.forename: Hanna
authors.initials: H
authors.lastname: Mertgens
authors.affiliation: Max Planck Institute for Neurological Research, Gleueler Str. 50, 50931 Koeln, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Backes
authors.affiliation: Max Planck Institute for Neurological Research, Gleueler Str. 50, 50931 Koeln, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Himmelreich
authors.affiliation: Max Planck Institute for Neurological Research, Gleueler Str. 50, 50931 Koeln, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Neumaier
authors.affiliation: Max Planck Institute for Neurological Research, Gleueler Str. 50, 50931 Koeln, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Graf
authors.affiliation: Max Planck Institute for Neurological Research, Gleueler Str. 50, 50931 Koeln, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Mies
mesh_terms: D000818:Animals; D020771:Anterior Cerebral Artery / Q000473:pathology*; D000983:Antipyrine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D020520:Brain Infarction / Q000175:diagnosis* / Q000209:etiology; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D018450:Disease Progression; D019332:Endothelin-1 / Q000633:toxicity; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D020244:Infarction, Middle Cerebral Artery / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D007554:Isotopes / Q000493:pharmacokinetics; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D001523:Mental Disorders / Q000175:diagnosis / Q000209:etiology*; D049268:Positron-Emission Tomography; D051381:Rats; D013997:Time Factors
chemical_list: D019332:Endothelin-1; D007554:Isotopes; D019788:Fluorodeoxyglucose F18; D000983:Antipyrine; C008135:iodoantipyrine
keywords: Anterior cerebral artery occlusion; Behavior; Cerebral blood flow; Cerebral glucose metabolism; Decision-making; Executive functions; Positron emission tomography