TY - JOUR
T1 - Six-Month ischemic mice show sensorimotor and cognitive deficits associated with brain atrophy and axonal disorganization
AU - Zanier, Elisa R.
AU - Pischiutta, Francesca
AU - Villa, Pia
AU - Paladini, Alessandra
AU - Montinaro, Mery
AU - Micotti, Edoardo
AU - Orrù, Alessandro
AU - Cervo, Luigi
AU - De Simoni, Maria Grazia
PY - 2013/9
Y1 - 2013/9
N2 - Summary: 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 30 min transient middle cerebral artery occlusion (tMCAo) or sham surgery. Sensorimotor deficits, exploratory behavior, and cognitive functions were evaluated up to 6 months. 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 24 weeks 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 6 months 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.
AB - Summary: 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 30 min transient middle cerebral artery occlusion (tMCAo) or sham surgery. Sensorimotor deficits, exploratory behavior, and cognitive functions were evaluated up to 6 months. 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 24 weeks 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 6 months 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.
KW - Behavior
KW - Brain damage
KW - Brain ischemia
KW - Diffusion tensor imaging
KW - Mice
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U2 - 10.1111/cns.12128
DO - 10.1111/cns.12128
M3 - Article
C2 - 23742688
AN - SCOPUS:84882898700
VL - 19
SP - 695
EP - 704
JO - CNS Neuroscience and Therapeutics
JF - CNS Neuroscience and Therapeutics
SN - 1755-5930
IS - 9
ER -