AUTHOR=Zhu Tiantian , Zhu Moli , Qiu Yue , Wu Zeqing , Huang Ning , Wan Guangrui , Xu Jian , Song Ping , Wang Shuangxi , Yin Yaling , Li Peng TITLE=Puerarin Alleviates Vascular Cognitive Impairment in Vascular Dementia Rats JOURNAL=Frontiers in Behavioral Neuroscience VOLUME=15 YEAR=2021 URL=https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2021.717008 DOI=10.3389/fnbeh.2021.717008 ISSN=1662-5153 ABSTRACT=

Cerebral ischemia triggers vascular dementia (VD), which is characterized by memory loss, cognitive deficits, and vascular injury in the brain. Puerarin (Pur) represents the major isoflavone glycoside of Radix Puerariae, with verified neuroprotective activity and cardiovascular protective effects. However, whether Pur ameliorates cognitive impairment and vascular injury in rats with permanent occlusion of bilateral common carotid arteries (BCCAO) remains unknown. This work aimed to assess Pur’s effects on BCCAO-induced VD and to dissect the underlying mechanisms, especially examining the function of transient receptor potential melastatin-related 2 (TRPM2) in alleviating cognitive deficits and vascular injuries. Rats with BCCAO developed VD. Pur (50, 100, and 150 mg/kg) dose-dependently attenuated the pathological changes, increased synaptic structural plasticity in the dorsal CA1 hippocampal region and decreased oxidative stress, which eventually reduced cognitive impairment and vascular injury in BCCAO rats. Notably, Pur-improved neuronal cell loss, synaptic structural plasticity, and endothelial vasorelaxation function might be mediated by the reactive oxygen species (ROS)-dependent TRPM2/NMDAR pathway, evidenced by decreased levels of ROS, malondialdehyde (MDA), Bax, Bax/Bcl2, and TRPM2, and increased levels of superoxide dismutase (SOD), Bcl2, and NR2A. In conclusion, Pur has therapeutic potential for VD, alleviating neuronal cell apoptosis and vascular injury, which may be related to the ROS-dependent TRPM2/NMDAR pathway.