title: Novel application of a Radial Water Tread maze can distinguish cognitive deficits in mice with traumatic brain injury.
abstract: The use of forced-swim, rat-validated cognition tests in mouse models of traumatic brain injury (TBI) raises methodological concerns; such models are vulnerable to a number of confounding factors including impaired motor function and stress-induced non-compliance (failure to swim). This study evaluated the ability of a Radial Water Tread (RWT) maze, designed specifically for mice, that requires no swimming to distinguish mice with controlled cortical impact (CCI) induced TBI and Sham controls.
  
  
  
  Ten-week-old, male C57BL6/J mice were randomly assigned to receive either Sham (n=14) or CCI surgeries (n=15). Mice were tested for sensorimotor deficits via Gridwalk test and Noldus CatWalk gait analysis at 1 and 32days post-injury. Mice received RWT testing at either 11days (early time point) or 35days (late time point) post-injury.
  
  
  
  Compared to Sham-treated animals, CCI-induced TBI resulted in significant impairment in RWT maze performance. Additionally, CCI injured mice displayed significant deficits on the Gridwalk test at both 1day and 32days post-injury, and impairment in the CatWalk task at 1day, but not 32days, compared to Shams.
  
  
  
  The Radial Water Tread maze capitalizes on the natural tendency of mice to avoid open areas in favor of hugging the edges of an apparatus (thigmotaxis), and replaces a forced-swim model with water shallow enough that the animal is not required to swim, but aversive enough to motivate escape. Our findings indicate the RWT task is a sensitive species-appropriate behavioral test for evaluating spatial memory impairment in a mouse model of TBI.
authors.affiliation: Department of Radiology, University of Washington, Seattle, WA, USA.
authors.forename: Marcella M
authors.initials: MM
authors.lastname: Cline
authors.affiliation: Department of Radiology, University of Washington, Seattle, WA, USA.
authors.forename: Josh C
authors.initials: JC
authors.lastname: Yumul
authors.affiliation: Department of Radiology, University of Washington, Seattle, WA, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Hysa
authors.affiliation: Department of Radiology, University of Washington, Seattle, WA, USA.
authors.forename: Dalia
authors.initials: D
authors.lastname: Murra
authors.affiliation: Department of Radiology, University of Washington, Seattle, WA, USA; Department of Radiology, University of Utah, Salt Lake City, UT, USA.
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Garwin
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, WA, USA; Geriatric Research Education and Clinical Center (GRECC), VA Puget Sound Health Care System, Seattle, WA, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Cook
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Warren C
authors.initials: WC
authors.lastname: Ladiges
authors.affiliation: Department of Radiology, University of Washington, Seattle, WA, USA; Department of Radiology, University of Utah, Salt Lake City, UT, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Minoshima
authors.affiliation: Department of Radiology, University of Washington, Seattle, WA, USA; Department of Radiology, University of Utah, Salt Lake City, UT, USA. Electronic address: donna.cross@hsc.utah.edu.
authors.forename: Donna J
authors.initials: DJ
authors.lastname: Cross
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D000070642:Brain Injuries, Traumatic / Q000150:complications / Q000175:diagnosis / Q000523:psychology*; D003072:Cognition Disorders / Q000175:diagnosis* / Q000209:etiology; D004195:Disease Models, Animal; D005684:Gait; D008297:Male; D018782:Maze Learning; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D009483:Neuropsychological Tests
keywords: Behavioral testing; Cognitive testing; Controlled-cortical impact; Traumatic brain injury; Water maze