Progressive cognitive deficits in a mouse model of recurrent photothrombotic stroke.
OBJECTIVE
In spite of its high disease burden, there is no specific treatment for multi-infarct dementia. The preclinical evaluation of candidate drugs is limited because an appropriate animal model is lacking. Therefore, we aimed to evaluate whether a mouse model of recurrent photothrombotic stroke is suitable for the preclinical investigation of multi-infarct dementia.


METHODS
Recurrent photothrombotic cortical infarcts were induced in 25 adult C57BL/6 mice. Twenty-five sham-operated animals served as controls. The object recognition test and the Morris water maze test were performed >6 weeks to assess cognitive deficits. Afterward, histological analyses were performed to characterize histopathologic changes associated with recurrent photothrombotic infarcts.


RESULTS
After the first infarct, the object recognition test showed a trend toward an impaired formation of recognition memories (P=0.08), and the Morris Water Maze test revealed significantly impaired spatial learning and memory functions (P<0.05). After recurrent infarcts, the object recognition test showed significant recognition memory deficits (P<0.001) and the Morris water maze test demonstrated persisting spatial learning and memory deficits (P<0.05). Histological analyses revealed remote astrogliosis in the hippocampus.


CONCLUSIONS
Our results show progressive cognitive deficits in a mouse model of recurrent photothrombotic stroke. The presented model resembles the clinical features of human multi-infarct dementia and enables the investigation of its pathophysiological mechanisms and the evaluation of treatment strategies.
From the Department of Neurology, University of Münster, Münster, Germany (A.S., K.D., J.-K.S., B.G., M.H., T.D., J.M.); and Department of Neurology, Bethel-EvKB, Bielefeld, Germany (W.-R.S.). antje.schmidt@ukmuenster.de.
Antje
A
Schmidt
From the Department of Neurology, University of Münster, Münster, Germany (A.S., K.D., J.-K.S., B.G., M.H., T.D., J.M.); and Department of Neurology, Bethel-EvKB, Bielefeld, Germany (W.-R.S.).
Kai
K
Diederich
From the Department of Neurology, University of Münster, Münster, Germany (A.S., K.D., J.-K.S., B.G., M.H., T.D., J.M.); and Department of Neurology, Bethel-EvKB, Bielefeld, Germany (W.-R.S.).
Jan-Kolja
JK
Strecker
From the Department of Neurology, University of Münster, Münster, Germany (A.S., K.D., J.-K.S., B.G., M.H., T.D., J.M.); and Department of Neurology, Bethel-EvKB, Bielefeld, Germany (W.-R.S.).
Birgit
B
Geng
From the Department of Neurology, University of Münster, Münster, Germany (A.S., K.D., J.-K.S., B.G., M.H., T.D., J.M.); and Department of Neurology, Bethel-EvKB, Bielefeld, Germany (W.-R.S.).
Maike
M
Hoppen
From the Department of Neurology, University of Münster, Münster, Germany (A.S., K.D., J.-K.S., B.G., M.H., T.D., J.M.); and Department of Neurology, Bethel-EvKB, Bielefeld, Germany (W.-R.S.).
Thomas
T
Duning
From the Department of Neurology, University of Münster, Münster, Germany (A.S., K.D., J.-K.S., B.G., M.H., T.D., J.M.); and Department of Neurology, Bethel-EvKB, Bielefeld, Germany (W.-R.S.).
Wolf-Rüdiger
WR
Schäbitz
From the Department of Neurology, University of Münster, Münster, Germany (A.S., K.D., J.-K.S., B.G., M.H., T.D., J.M.); and Department of Neurology, Bethel-EvKB, Bielefeld, Germany (W.-R.S.).
Jens
J
Minnerup
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D015161:Dementia, Multi-Infarct / Q000209:etiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D020767:Intracranial Thrombosis / Q000150:complications; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D021641:Recognition, Psychology / Q000502:physiology; D012008:Recurrence
animal model; cognition; poststroke dementia; stroke