Novel application of a Radial Water Tread maze can distinguish cognitive deficits in mice with traumatic brain injury.
Marcella M Cline, Josh C Yumul, Lisa Hysa, Dalia Murra, Gregory G Garwin, David G Cook, Warren C Ladiges, Satoshi Minoshima, Donna J Cross
Author Information
Marcella M Cline: Department of Radiology, University of Washington, Seattle, WA, USA.
Josh C Yumul: Department of Radiology, University of Washington, Seattle, WA, USA.
Lisa Hysa: Department of Radiology, University of Washington, Seattle, WA, USA.
Dalia Murra: Department of Radiology, University of Washington, Seattle, WA, USA.
Gregory G Garwin: Department of Radiology, University of Washington, Seattle, WA, USA; Department of Radiology, University of Utah, Salt Lake City, UT, USA.
David G Cook: 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.
Warren C Ladiges: Department of Comparative Medicine, University of Washington, Seattle, WA, USA.
Satoshi Minoshima: Department of Radiology, University of Washington, Seattle, WA, USA; Department of Radiology, University of Utah, Salt Lake City, UT, USA.
Donna J Cross: 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.
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
