Sensorimotor behavioral effects of endothelin-1 induced small cortical infarcts in C57BL/6 mice

Abstract

Mouse models have not paralleled rat models of stroke in advances in sensitive, species appropriate measures of neurological and behavioral recovery. Most available tests of mouse sensorimotor function are adaptations of those originally developed in rats and may not be as sensitive in detecting behavioral deficits after small cortical lesions in mice. Our purpose was to test the use of a vasoconstricting peptide, endothelin-1 (ET-1), to produce focal infarcts of the mouse sensorimotor cortex and to establish a behavioral test battery sensitive to resulting sensorimotor deficits. Young adult (3–5-month-old) male C57BL/6 mice received intracortical infusions of ET-1 that produced unilateral lesions of the forelimb region of the sensorimotor cortex, intracortical infusions of sterile saline, or sham surgeries. Pre-operatively and at various time points over 3 weeks post-surgery, they were administered a test battery that included measures of sensorimotor asymmetry (Corner and Bilateral Tactile Stimulation Tests), coordinated forepaw use (Cylinder and Ladder Rung Tests), and dexterous forepaw function (Pasta Matrix Reaching Test). ET-1 infusions resulted in consistently placed, focal cortical infarcts and forelimb impairments as measured with the Ladder Rung, Bilateral Tactile Stimulation, and Pasta Matrix Reaching Tests. On the Bilateral Tactile Stimulation and Pasta Matrix Reaching Tests, impairments persisted throughout the time span of observation (26 days). These results support ET-1 as a viable option for creating small, reproducible lesions of anatomical subregions in the mouse neocortex that result in lasting functional impairments in the forelimb, as observed with sufficiently sensitive measures.