Chronic cerebral hypoperfusion induced by right unilateral common carotid artery occlusion causes delayed white matter lesions and cognitive impairment in adult mice.
Some lines of evidence have suggested that subcortical ischemic vascular dementia (SIVD) is a common form of vascular dementia (VaD), and that its pathological changes are the development of ischemic white matter (WM) lesions under chronic hypoperfusion and lacunes. Here, we have developed a novel mouse model of VaD with WM lesions, which was induced by right unilateral common carotid artery occlusion (rUCCAO). The mice subjected to rUCCAO exhibited chronic cerebral hypoperfusion in the cerebral hemisphere ipsilateral to rUCCAO monitored using a laser-Doppler flow meter (p<0.01), and significant WM damage in the corpus callosum (p<0.05) and deficits in object recognition test correlated with the damage of frontal-subcortical circuits (p<0.01). However, no differences in spontaneous alternation or spontaneous motor activity were observed. Furthermore, the levels of pro-inflammatory cytokines, such as interleukin-1beta (IL-1beta) and interleukin-6 (IL-6), significantly increased (p<0.01), and those of anti-inflammatory cytokines, such as interleukin-4 (IL-4) and interleukin-10 (IL-10), significantly decreased in the ischemic brain (p<0.05). These results suggest that this model is a useful tool for investigating the associations among inflammatory reactions, cognitive impairment, and WM damage, which may help elucidating the pathomechanism of VaD, particularly SIVD.
Yoshizaki
Kaichi
K
Department of Vascular Dementia Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3, Gengo, Morioka, Obu-city, Aichi 474-8511, Japan.
Adachi
Kayo
K
Kataoka
Seiko
S
Watanabe
Atsushi
A
Tabira
Takeshi
T
Takahashi
Keikichi
K
Wakita
Hideaki
H
D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002340:Carotid Artery Diseases / Q000150:complications*; D002560:Cerebrovascular Circulation / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000150:complications / Q000209:etiology / Q000473:pathology; D003072:Cognition Disorders / Q000209:etiology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007839:Functional Laterality / Q000502:physiology*; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D009457:Neuroglia / Q000473:pathology*; D009483:Neuropsychological Tests; D010477:Perfusion / Q000379:methods; D013997:Time Factors
D016207:Cytokines