Luseogliflozin, a sodium-glucose cotransporter-2 inhibitor, reverses cerebrovascular dysfunction and cognitive impairments in 18-mo-old diabetic animals
Shaoxun Wang, Feng Jiao, Jane J. Border, Xing Fang, Reece F. Crumpler, Yedan Liu, Huawei Zhang, Joshua R. Jefferson, Ya Guo, P. Elliott, Kirby N. Thomas, Luke Strong, Austin Urvina, Baoying Zheng, Arjun Hari Rijal, Stanley V. Smith, Hongwei Yu, Richard J. Roman, Fan Fan
Abstract
This study demonstrates that luseogliflozin, a sodium-glucose cotransporter-2 inhibitor, improved CBF autoregulation in association with reduced vascular oxidative stress and AGEs production in the cerebrovasculature of 18-mo-old DM rats. SGLT2i also prevented BBB leakage, impaired functional hyperemia, neurodegeneration, and cognitive impairment seen in DM rats. Luseogliflozin did not have direct constrictive effects on VSMCs and MCAs isolated from normal rats. These results provide evidence that normalization of hyperglycemia with an SGLT2i can reverse cerebrovascular dysfunction and cognitive impairments in rats with long-standing hyperglycemia, possibly by ameliorating oxidative stress-caused vascular damage.