Supporting data for "The role and mechanisms of neuroinflammation and glucose metabolism in the postoperative neurocognitive disorders"

PNDs has been observed for decades, which cause lower life quality, delayed recovery, and heavy medical burdens for both individuals and the community. Considering that an increasing population undergoes surgery, and over one-third are aged patients, this common surgical complication is becoming a great challenge for the society. Previous evidence has already showed that neuroinflammation and blood-brain barrier disruption are two critical pathological changes in PNDs, while their underlying mechanisms remain unclear, which make it difficult to find potential therapeutic targets. 

To illustrate the association between neuroinflammation and cognitive functions, this project firstly explored the feature of postoperative reactive astrocytes and searched for the key secreted factor that accelerates cognitive impairment by using RNA-sequencing and RNA silencing. The results demonstrated that surgery induced neurotoxic astrocyte reactivation, which contributed to the development of PNDs by C3-mediated microglial synaptic engulfment. Thus, C3 could be a potential therapeutic target for PNDs. 

Moreover, aged surgical mice did not have neuroinflammatory responses but displayed significant disruption of the blood-brain barrier with GLUT1 downregulation. To investigate the role of GLUT1 in the blood-brain barrier in PNDs, this project further evaluated the changes of metabolites in the hippocampus and examined their association with cognitive impairment by GC-MS technology and conditional overexpression of GLUT1 in the blood-brain barrier. The results illustrated that surgery-induced GLUT1 downregulation in the blood-brain barrier led to a decrease in glycolytic metabolites, which contributed to postoperative cognitive deficits.

In conclusion, this project provides a new interpretation of the pathological mechanism in PNDs and observes several potential targets for the therapeutic treatment of PNDs, which is worthy of further investigation.