Lipo-prostaglandin El modifies cognitive impairment in rats with vascular cognitive impairment by promoting angiogenesis via the VEGF/VEGFR pathway

The pathological mechanism of vascular cognitive impairment (VCI) involves ischemic lesions in the hippocampus. Prostaglandin [E.sub.1] ([PGE.sub.1]) serves roles in the promotion of vascular endothelial growth factor (VEGF) expression, angiogenesis and enhances blood flow to ischemic regions. However, the effect of [PGE.sub.1] on cognitive function in VCI rats and the underlying mechanism are unknown. In the current study, learning and memory function in VCI rats treated by lipo-[PGE.sub.1] injection was assessed through Morris Water Maze test. Furthermore, the histological alterations, blood vessel numbers in the hippocampal CA1 region and relative VEGF protein and mRNA expression were researched. The results confirmed that VCI rats treated with lipo-[PGE.sub.1] presented improved cognitive function, less neuronal cell loss, a greater number of blood vessels in the hippocampal region and higher VEGF protein and mRNA expression. However, the role of lipo-[PGE.sub.1] in VCI rats can be inhibited by SU5416 (a specific VEGFR2 antagonist). The results indicated that lipo-[PGE.sub.1] may alleviate cognitive deficits in VCI rats. The underlying mechanism may be associated with angiogenesis promoted by lipo-[PGE.sub.1], which may involve the VEGF/VEGFR pathway. These findings may have therapeutic implications for cognitive impairment induced by hypoperfusion or chronic ischemic lesions. Key words: lipo-[PGE.sub.1], angiogenesis, vascular endothelial growth factor, vascular endothelial growth factor receptor antagonist, cognitive impairment