Pericyte loss impairs BBB and cognitive function in aged mice after anesthesia/surgery

Abstract Objective: Studies have shown that perioperative neurocognitive disorder (PND) was related to blood–brain barrier (BBB) dysfunction and neuroinflammation. However, the effects of anesthesia/surgery on BBB integrity and composition and the associated mechanisms of BBB dysfunction remain incompletely elucidated. This study aimed to clarify the pathogenesis of PND. Methods: In this study, we established a PND model via sevoflurane anesthesia and tibial fracture surgery in 2-month-old and 16-month-old male C57BL/6 mice. On the third postoperative day, the mice were subjected to behavioral testing or sacrificed to collect brain tissue. The progression of hippocampal BBB disruption and neuroinflammation were detected using immunofluorescence. We also used Western blotting to measure the levels of plasma-derived protein immunoglobulin G (IgG) and albumin in the hippocampus to assess the leakage of the BBB. Results: Non-operative aged mice did not experience age-related cognitive decline and BBB disruption compared with Non-operative younger mice, but only increased glial cell activity. Anesthesia/Surgery damaged cognitive function, reduced pericyte coverage, decreased the length of capillaries and levels of occludin and claudin-5, exacerbated IgG and albumin accumulation in the hippocampus, and enhanced the activation of microglia and astrocytes in the hippocampus of old mice. However, these negative effects did not occur in young mice. Conclusions: Our study showed that the loss of pericytes led to increased BBB permeability and neuroinflammation after anesthesia/surgery in aged mice, ultimately resulting in cognitive dysfunction.