%0 Journal Article
%T Lessons from a Mouse Model Characterizing Features of Vascular Cognitive Impairment with White Matter Changes
%A Masafumi Ihara
%A Hidekazu Tomimoto
%J Journal of Aging Research
%D 2011
%I Hindawi Publishing Corporation
%R 10.4061/2011/978761
%X With the demographic shift in age in advanced countries inexorably set to progress in the 21st century, dementia will become one of the most important health problems worldwide. Vascular cognitive impairment is the second most common type of dementia after Alzheimer's disease and is frequently responsible for the cognitive decline of the elderly. It is characterized by cerebrovascular white matter changes; thus, in order to investigate the underlying mechanisms involved in white matter changes, a mouse model of chronic cerebral hypoperfusion has been developed, which involves the narrowing of the bilateral common carotid arteries with newly designed microcoils. The purpose of this paper is to provide a comprehensive summary of the achievements made with the model that shows good reproducibility of the white matter changes characterized by blood-brain barrier disruption, glial activation, oxidative stress, and oligodendrocyte loss following chronic cerebral hypoperfusion. Detailed characterization of this model may help to decipher the substrates associated with impaired memory and move toward a more integrated therapy of vascular cognitive impairment. 1. Introduction Subcortical ischemic vascular dementia (SIVD) is characterized by white matter (WM) changes and lacunar infarctions, which occur as a result of a reduction in cerebral blood flow (CBF) over an extended period of time, causing small vessel changes [1¨C3]. Cerebrovascular WM lesions, neurodegenerative manifestations characterized by hyperintense signals on magnetic resonance images, are frequently associated with aging and are responsible for the cognitive decline in the elderly population [1¨C7]. Chronic cerebral hypoperfusion is likely to cause such WM lesions as CBF is decreased in these patients [2, 8]; indeed, similar WM lesions can be induced in rats, gerbils, and mice after chronic cerebral hypoperfusion, with experimental conditions mimicking chronic cerebral ischemia in humans [9¨C11]. These model animals can be generated by bilateral common carotid artery (CCA) occlusion in rats (2-vessel occlusion (2VO)) [9, 12, 13] or in mice [14], bilateral CCA stenosis in mice (BCAS) [10] or in gerbils [11], and unilateral CCA occlusion in mice [15]. Nonhuman primates appear to represent the best model for the study of WM lesions, because they have well-developed WM and vascular architectures which closely resemble those in human brains [16]. Nevertheless, most experiments studying chronic cerebral hypoperfusion have been performed in rodents because of the ease of handling and higher acceptability
%U http://www.hindawi.com/journals/jar/2011/978761/