title: Molecular Mechanisms of Vascular Dementia: What Can Be Learned from Animal Models of Chronic Cerebral Hypoperfusion?
abstract: Vascular dementia (VD) is defined as a progressive neurodegenerative disease of cognitive decline, attributable to cerebrovascular factors. Numerous studies have demonstrated that chronic cerebral hypoperfusion (CCH) is associated with the initiation and progression of VD and Alzheimer's disease (AD). Suitable animal models were established to replicate such pathological condition in experimental research, which contributes largely to comprehending causal relationships between CCH and cognitive impairment. The most widely used experimental model of VD and CCH is permanent bilateral common carotid artery occlusion in rats. In CCH models, changes of learning and memory, cerebral blood flow (CBF), energy metabolism, and neuropathology initiated by ischemia were revealed. However, in order to achieve potential therapeutic targets, particular mechanisms in cognitive and neuropathological changes from CCH to dementia should be investigated. Recent studies have shown that hypoperfusion resulted in a chain of disruption of homeostatic interactions, including oxidative stress, neuroinflammation, neurotransmitter system dysfunction, mitochondrial dysfunction, disturbance of lipid metabolism, and alterations of growth factors. Evidence from experimental studies that elucidate the damaging effects of such imbalances suggests their critical roles in the pathogenesis of VD. The present review provides a summary of the achievements in mechanisms made with the CCH models, permits an understanding of the causative role played by CCH in VD, and highlights preventative and therapeutic prospects.
authors.affiliation: Acupuncture and Moxibustion Department, Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University, 23 Meishuguanhou Street, Dongcheng District, Beijing, 100010, China.
authors.forename: Si-Qi
authors.initials: SQ
authors.lastname: Du
authors.affiliation: Acupuncture and Moxibustion Department, Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University, 23 Meishuguanhou Street, Dongcheng District, Beijing, 100010, China.
authors.forename: Xue-Rui
authors.initials: XR
authors.lastname: Wang
authors.affiliation: Beijing University of Chinese Medicine, 11 Beisanhuan East Road, Chaoyang District, Beijing, 100029, China.
authors.forename: Ling-Yong
authors.initials: LY
authors.lastname: Xiao
authors.affiliation: Beijing University of Chinese Medicine, 11 Beisanhuan East Road, Chaoyang District, Beijing, 100029, China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Tu
authors.affiliation: Acupuncture and Moxibustion Department, Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University, 23 Meishuguanhou Street, Dongcheng District, Beijing, 100010, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Acupuncture and Moxibustion Department, Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University, 23 Meishuguanhou Street, Dongcheng District, Beijing, 100010, China.
authors.forename: Tian
authors.initials: T
authors.lastname: He
authors.affiliation: Acupuncture and Moxibustion Department, Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University, 23 Meishuguanhou Street, Dongcheng District, Beijing, 100010, China. lcz623780@126.com.
authors.forename: Cun-Zhi
authors.initials: CZ
authors.lastname: Liu
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000473:pathology; D002560:Cerebrovascular Circulation; D015140:Dementia, Vascular / Q000503:physiopathology*; D004195:Disease Models, Animal; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress
keywords: Chronic cerebral hypoperfusion; Cognition; Neuroinflammation; Oxidative stress; Vascular dementia