Rutin protects against cognitive deficits and brain damage in rats with chronic cerebral hypoperfusion.
Chronic cerebral hypoperfusion is a critical causative factor for the development of cognitive decline and dementia in the elderly, which involves many pathophysiological processes. Consequently, inhibition of several pathophysiological pathways is an attractive therapeutic strategy for this disorder. Rutin, a biologically active flavonoid, protects the brain against several insults through its antioxidant and anti-inflammatory properties, but its effect on cognitive deficits and brain damage caused by chronic cerebral hypoperfusion remains unknown. Here, we investigated the neuroprotective effect of rutin on cognitive impairments and the potential mechanisms underlying its action in rats with chronic cerebral hypoperfusion.



We used Sprague-Dawley rats with permanent bilateral common carotid artery occlusion (BCCAO), a well-established model of chronic cerebral hypoperfusion. After rutin treatment for 12 weeks, the neuroprotective effect of rutin in rats was evaluated by behavioural tests, biochemical and histopathological analyses.



BCCAO rats showed marked cognitive deficits, which were improved by rutin treatment. Moreover, BCCAO rats exhibited central cholinergic dysfunction, oxidative damage, inflammatory responses and neuronal damage in the cerebral cortex and hippocampus, compared with sham-operated rats. All these effects were significantly alleviated by treatment with rutin.



Our results provide new insights into the pharmacological actions of rutin and suggest that rutin has multi-targeted therapeutical potential on cognitive deficits associated with conditions with chronic cerebral hypoperfusion such as vascular dementia and Alzheimer's disease.
Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Jie
J
Qu
Qiong
Q
Zhou
Ying
Y
Du
Wei
W
Zhang
Miao
M
Bai
Zhuo
Z
Zhang
Ye
Y
Xi
Zhuyi
Z
Li
Jianting
J
Miao
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D017628:Microglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D012431:Rutin / Q000494:pharmacology / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism
D016207:Cytokines; D018696:Neuroprotective Agents; D008315:Malondialdehyde; D012431:Rutin; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000109:Acetylcholine
chronic cerebral hypoperfusion; cognitive deficits; neuroinflammation; oxidative stress; rutin