Pericyte loss impairs the blood–brain barrier and cognitive function in aged mice after anesthesia/surgery

Abstract

Aims: This study was designed to investigate the role of pericytes in the pathogenesis of perioperative neurocognitive disorder (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 blood–brain barrier (BBB) disruption and neuroinflammation was detected using transmission electron microscope and 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: Aged mice did not experience age-related cognitive decline and BBB disruption compared with 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, destroyed the structure of the BBB, exacerbated IgG and albumin accumulation in the hippocampus, and enhanced the activation of microglia and astrocytes in the hippocampus of aged mice. However, these negative effects did not occur in young mice. Conclusion: 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.

Keywords

• Anesthesia/surgery
• Blood–brain barrier
• Neuroinflammation
• Pericyte
• Perioperative neurocognitive disorder