title: A reproducible Endothelin-1 model of forelimb motor cortex stroke in the mouse.
abstract: BACKGROUND
  Despite the availability of numerous transgenic mouse lines to study the role of individual genes in promoting neural repair following stroke, few studies have availed of this technology, primarily due to the lack of a reproducible ischemic injury model in the mouse. Intracortical injections of Endothelin-1 (ET1) a potent vasoconstrictive agent, reliably produces focal infarcts with concomitant behavioral deficits in rats. In contrast, ET1 infarcts in mice are significantly smaller and do not generate consistent behavioral deficits.
  
  
  METHODS
  We have modified the ET1 ischemia model to target the anterior forelimb motor cortex (aFMC) and show that this generates a reproducible focal ischemic injury in mice with consistent behavioral deficits. Furthermore, we have developed a novel analysis of the cylinder test by quantifying paw-dragging behavior.
  
  
  RESULTS
  ET1 injections which damage deep layer neurons in the aFMC generate reproducible deficits on the staircase test. Cylinder test analysis showed no forelimb asymmetry post-injection; however, we observed a novel paw-dragging behavior in mice which is a positive sign of damage to the FMC.
  
  
  METHODS
  Previous ET1 studies have demonstrated inconsistent behavioral deficits; however, targeting ET1 injections to the aFMC reliably results in staircase deficits. We show that analysis of paw-dragging behavior in the cylinder test is a more sensitive measure of damage to the FMC than the classical forelimb asymmetry analysis.
  
  
  CONCLUSIONS
  We have developed a focal ischemic injury model in the mouse that results in reproducible behavioral deficits and can be used to test future regenerative therapies.
authors.affiliation: BioMedical Sciences, Faculty of Medicine Memorial University of Newfoundland, 300 Prince Phillip Dr., St. John's, NL A1B 3V6, Canada; Heart and Stroke Foundation of Canada, Canadian Partnership for Stroke Recovery, Canada.
authors.forename: R Brian
authors.initials: RB
authors.lastname: Roome
authors.affiliation: BioMedical Sciences, Faculty of Medicine Memorial University of Newfoundland, 300 Prince Phillip Dr., St. John's, NL A1B 3V6, Canada; Heart and Stroke Foundation of Canada, Canadian Partnership for Stroke Recovery, Canada.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Bartlett
authors.affiliation: BioMedical Sciences, Faculty of Medicine Memorial University of Newfoundland, 300 Prince Phillip Dr., St. John's, NL A1B 3V6, Canada; Heart and Stroke Foundation of Canada, Canadian Partnership for Stroke Recovery, Canada; Department Cellular & Molecular Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, ON K1H 8M5, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Jeffers
authors.affiliation: BioMedical Sciences, Faculty of Medicine Memorial University of Newfoundland, 300 Prince Phillip Dr., St. John's, NL A1B 3V6, Canada; Heart and Stroke Foundation of Canada, Canadian Partnership for Stroke Recovery, Canada.
authors.forename: Jieying
authors.initials: J
authors.lastname: Xiong
authors.affiliation: BioMedical Sciences, Faculty of Medicine Memorial University of Newfoundland, 300 Prince Phillip Dr., St. John's, NL A1B 3V6, Canada; Heart and Stroke Foundation of Canada, Canadian Partnership for Stroke Recovery, Canada; Department Cellular & Molecular Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, ON K1H 8M5, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Dale
authors.initials: D
authors.lastname: Corbett
authors.affiliation: BioMedical Sciences, Faculty of Medicine Memorial University of Newfoundland, 300 Prince Phillip Dr., St. John's, NL A1B 3V6, Canada; Heart and Stroke Foundation of Canada, Canadian Partnership for Stroke Recovery, Canada. Electronic address: j.vanderluit@mun.ca.
authors.forename: Jacqueline L
authors.initials: JL
authors.lastname: Vanderluit
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D002452:Cell Count; D004195:Disease Models, Animal; D019332:Endothelin-1; D005552:Forelimb / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009044:Motor Cortex / Q000473:pathology / Q000503:physiopathology*; D009069:Movement Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000473:pathology / Q000502:physiology; D011897:Random Allocation; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D020521:Stroke / Q000150:complications / Q000473:pathology / Q000503:physiopathology*
chemical_list: D019332:Endothelin-1
keywords: Behavioral test; Cylinder test; Forelimb motor cortex; Injury volume; Neural precursor cells; Staircase test; Subventricular zone