Six-Month Ischemic Mice Show Sensorimotor and Cognitive Deficits Associated with Brain Atrophy and Axonal Disorganization

Aims To identify long-term sensorimotor and cognitive deficits and to evaluate structural alterations in brain ischemic mice. Methods C57Bl/6J male mice were subjected to 30min transient middle cerebral artery occlusion (tMCAo) or sham surgery. Sensorimotor deficits, exploratory behavior, and cognitive functions were evaluated up to 6months. Cortical and subcortical damage were analyzed by MRI multiparameter analysis and histopathology. Results tMCAo mice showed significant sensorimotor deficits in the rotarod, negative geotaxis, neuroscore, and beam walk tests. They also showed impairment in exploratory behavior in the open field test and in spatial learning in the Morris water maze. T2-weighted MRI revealed a volume reduction in injured brain areas at 12 and 24weeks postinjury. Brain atrophy was shown by MRI and conventional postmortem analysis. Diffusion tensor imaging on the external capsule showed increased values of axial and radial diffusivity. Fiber tracking revealed a reduction in the number and length of ipsilateral fibers. Conclusions tMCAo in mice induces sensorimotor and cognitive impairments detectable at least up to 6months postinjury, associated with brain atrophy, and axonal and myelin damage of the external capsule. These behavioral tests and anatomical investigations may represent important tools in translational studies in cerebral ischemia.