Inhibition of connexin 43 hemichannels improves postoperative cognitive function in aged mice

Aims: Postoperative cognitive dysfunction (POCD) is a neurological disorder associated with neuroinflammation. Connexin 43 (Cx43), an essential component of gap junction, plays a crucial role in neuroinflammation. The present study was designed to investigate the role of Cx43 in the process of POCD. Methods: POCD model was established in aged mice with internal fixation of tibial fractures. Cognitive function was examined using the Morris water maze test. Hippocampus was collected for reverse transcription polymerase chain reaction (RT-PCR), western blotting, and immunofluorescence assays. Results: In the water maze test, mice undergoing surgery took longer time to reach target platform than the controls. IL-1β and TNF-α mRNA expressions in the hippocampus were significantly increased in surgery mice. Cx43 protein presence in the hippocampus was increased in the surgery group. Treatment of Gap26, a specific blocker of Cx43 hemichannel, reduced the Cx43 protein presence, decreased mRNA expressions of IL-1β and TNF-α, and improved cognitive score in the maze test. Conclusion: Internal fixation of tibial fractures in aged mice induces Cx43 hemichannels opening and enhances neuroinflammation in the hippocampus, leading to cognitive impairment. Administration of Gap26 reduces neuroinflammation in the hippocampus and improves postoperative cognitive function.