Abstract
Background: The pathophysiological mechanisms underlying postoperative cognitive dysfunction (POCD) remain unclear over the years. Neuroinflammation caused by surgery has been recognized as an important element in the development of POCD. Many studies also suggest that the vagus nerve plays an important role in transmitting peripheral injury signals to the central nervous system (CNS) and the resultant neuroinflammation. Previously, we have demonstrated that brain mast cells (BMCs), as the “first responders”, play a vital role in neuroinflammation and POCD. However, how the vagus nerve communicates with BMCs in POCD has not yet been clarified.Methods: In the current study, we highlighted the role of the vagus nerve as a conduction highway in surgery-induced neuroinflammation for the first time. In our model, we tested if mice underwent unilateral cervical vagotomy (VGX) had less neuroinflammation compared to the shams after laparotomy (LP) at an early stage. To further investigate the roles of mast cells and glutamate in the process, we employed KitW-sh mice and primary bone marrow-derived MCs to verify the glutamate-NR2B axis on MCs once again.Results: Our results demonstrated that there were higher levels of glutamate and BMCs activation as early as 4 h after LP. Meanwhile, vagotomy could partially block the increases and reduce neuroinflammation caused by peripheral inflammation during the acute phase. Excitingly, inhibition of NR2B receptor and knockout of mast cells can attenuateneuroinflammation induced by glutamate.Conclusion: Taken together, our findings indicate that the vagus is a high-speed pathway in the transmission of peripheral inflammation to the CNS. Activation of BMCs triggered a neuroinflammatory cascade. Inhibition of NR2B receptor on BMCs can reduce glutamate-induced BMCs activation, neuroinflammation, and memory impairment, suggesting a novel treatment strategy for POCD.
Highlights
Postoperative cognitive dysfunction (POCD) is characterized by a decline in cognitive performance, memory, and learning following surgery, in aged patients (Yan et al, 2012)
We studied the effects of cervical vagotomy on the activation of microglia, impairment of hippocampal memory, and increases in inflammatory cytokine levels observed in mice followed by laparotomy 2 h later
We examined the expression levels of PSD95 and occludin using western blotting and found that they were significantly lower at 24 h in the sham + laparotomy (sham+LP) group than in the Cervical vagotomy (VGX)+LP group (Figure 3B)
Summary
Postoperative cognitive dysfunction (POCD) is characterized by a decline in cognitive performance, memory, and learning following surgery, in aged patients (Yan et al, 2012). Previous studies have shown that the incidence of POCD in aged patients undergoing non-cardiac surgery was 25.8% and 9.9% at 1 week and 3 months respectively. In patients undergoing cardiac surgery, the incidence of POCD was as high as 39% at 3 months (Steinmetz et al, 2009; Kok et al, 2014). Neuroinflammation caused by surgery has been recognized as an important element in the development of POCD. Many studies suggest that the vagus nerve plays an important role in transmitting peripheral injury signals to the central nervous system (CNS) and the resultant neuroinflammation. We have demonstrated that brain mast cells (BMCs), as the “first responders”, play a vital role in neuroinflammation and POCD. How the vagus nerve communicates with BMCs in POCD has not yet been clarified
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
