The Effects of Intraoperative Hypothermia on Postoperative Cognitive Function in the Rat Hippocampus and Its Possible Mechanisms.

Guangyan Xu,Yuguang Huang,Tianjia Li

doi:10.3390/brainsci12010096

Abstract

Intraoperative hypothermia is a common complication during operations and is associated with several adverse events. Postoperative cognitive dysfunction (POCD) and its adverse consequences have drawn increasing attention in recent years. There are currently no relevant studies investigating the correlation between intraoperative hypothermia and POCD. The aim of this study was to assess the effects of intraoperative hypothermia on postoperative cognitive function in rats undergoing exploratory laparotomies and to investigate the possible related mechanisms. We used the Y-maze and Morris Water Maze (MWM) tests to assess the rats’ postoperative spatial working memory, spatial learning, and memory. The morphological changes in hippocampal neurons were examined by haematoxylin-eosin (HE) staining and hippocampal synaptic plasticity-related protein expression. Activity-regulated cytoskeletal-associated protein (Arc), cyclic adenosine monophosphate-response element-binding protein (CREB), S133-phosphorylated CREB (p-CREB [S133]), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor 1 (AMPAR1), and S831-phosphorylated AMPAR1 (p-AMPAR1 [S831]) were evaluated by Western blotting. Our results suggest a correlation between intraoperative hypothermia and POCD in rats and that intraoperative hypothermia may lead to POCD regarding impairments in spatial working memory, spatial learning, and memory. POCD induced by intraoperative hypothermia might be due to hippocampal neurons damage and decreased expression of synaptic plasticity-related proteins Arc, p-CREB (S133), and p-AMPAR1 (S831).

Highlights

Intraoperative hypothermia is a common complication during operations; up to 25–70% of patients experience intraoperative hypothermia [1,2,3]
Our results show that intraoperative hypothermia can significantly inhibit hippocampal synaptic plasticity-related proteins, including Arc, p-cyclic adenosine monophosphate-response element-binding protein (CREB) (S133), and p-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor 1 (AMPAR1) (S831), indicating that intraoperative hypothermia impairs the postoperative cognitive function of rats by reducing the levels of hippocampal synaptic plasticity-related proteins
We found a correlation between intraoperative hypothermia and Postoperative cognitive dysfunction (POCD) in rats

Summary

Introduction

Numerous studies have revealed that intraoperative hypothermia is closely associated with several adverse events, including increased surgical blood loss and transfusion, shivering, morbid cardiac events, surgical site infection, delayed wound healing, and prolonged hospitalisation [4,5,6]. We published two independent observational studies, which revealed a high incidence of intraoperative hypothermia in China and identified its potential risk factors [2,7]. Postoperative cognitive dysfunction (POCD), a recognised clinical phenomenon characterised by impaired learning and memory, and decreased attention, has attracted increasing attention in recent years [9,10]. As one of the most common postoperative complications, POCD seriously affects patients’ postoperative rehabilitation, prolongs hospital stays, decreases long-term quality of life, and increases mortality, resulting in significant individual and societal burdens [11,12]. Many mechanisms, including apoptosis [13], neuroinflammation and oxidative stress [11,14,15], autophagy [16], and synaptic plasticity dysfunction [16,17] are involved in POCD, the exact molecular mechanism remains unknown

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