Supporting data of "GLUT1 downregulation in the cerebral microvasculature contributes to postoperative neurocognitive disorders in aged mice"

Advanced age is one of the major risk factors of perioperative neurocognitive disorders, and Blood-brain barrier dysfunction could be the contributor. Glucose transporter 1 (GLUT1) is dominantly expressed in the cerebral microvasculature and essential for glucose transport into the brain. Downregulation of GLUT1 correlates with dysregulated metabolism in the brain and cognitive impairment and may precede before cognitive symptoms. However, whether GLUT1 is affected by surgery and is involved in perioperative neurocognitive disorders has not been investigated. Here, we demonstrated that surgery-induced GLUT1 reduction in the blood-brain barrier correlated with cognitive impairment and diminished glucose metabolism, especially ATP levels. Enhanced microvascular GLUT1 expression alleviated cognitive decline with altered metabolic profiles but did not directly restore ATP generation. Further intranasal administration of a GLUT1 specific inhibitor abolished the protective effects of GLUT1 overexpression. Furthermore, surgery reduced tight junctions but GLUT1 overexpression mitigated this reduction, implying that GLUT1 affects blood-brain barrier integrity. These findings suggest that GLUT1 downregulation contributes to postoperative cognitive impairment in aged mice. This gives supports towards developing a therapeutic strategy that target GLUT1 to improve metabolic profile, blood-brain barrier permeability and cognitive function in perioperative neurocognitive disorders and neurodegenerative diseases.