Affiliations: [a]
Department of Anesthesiology, University of Virginia, Charlottesville, VA, USA
| [b]
Department of Anesthesiology, Fujian Medical University Union Hospital, Fuzhou, China
| [c]
Department of Anesthesiology, First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China
| [d]
Department of Anesthesiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Correspondence:
[*]
Correspondence to: Dr. Zhiyi Zuo, MD, PhD, Department of Anesthesiology, University of Virginia Health System, 1 Hospital Drive, PO Box 800710, Charlottesville, VA 22908-0710, USA. Tel.: +1 434 924 2283; Fax: +1 434 924 2105; E-mail: zz3c@virginia.edu.
Abstract: Background:Perioperative, modifiable factors contributing to perioperative neurocognitive disorders (PND) have not been clearly defined. Objective:To determine the contribution of anesthesia lengths and the degrees of surgical trauma to PND and neuroinflammation, a critical process for PND. Methods:Three-month-old C57BL/6J mice were subjected to 2 h or 6 h isoflurane anesthesia plus a 5 min or 15 min left common carotid artery exposure (surgery) in a factorial design (two factors: anesthesia with two levels and surgery with three levels). Their learning and memory were tested by Barnes maze and novel object recognition paradigms. Blood, spleen, and hippocampus were harvested for measuring interleukin (IL)-6 and IL-1β. Eighteen-month-old C57BL/6J mice (old mice) were subjected to 6 h isoflurane anesthesia or 2 h isoflurane anesthesia plus 15 min surgery and then had learning and memory tested. Results:Three-month-old mice with 15 min surgery (long surgery) under 2 h or 6 h anesthesia performed poorly in the learning and memory tests compared with controls. Anesthesia alone or anesthesia plus 5 min surgery did not affect mouse performance in these tests. Similarly, only mice with long surgery but not mice with other experimental conditions had increased IL-6 and IL-1β in the blood, spleen, and hippocampus and decreased spleen weights. Splenocytes were found in the hippocampus after surgery. Similarly, old mice with long surgery but not the mice with isoflurane anesthesia alone had poor performance in the Barnes maze and novel object recognition tests. Conclusion:Surgical trauma, but not anesthesia, contributes to the development of PND and neuroinflammation. Splenocytes may modulate these processes.
Keywords: Inflammatory cytokines, mice, postoperative cognitive dysfunction, spleen, surgery
