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

Guangyan Xu, Tianjia Li, Yuguang Huang, Guangyan Xu, Tianjia Li, Yuguang Huang

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).

Keywords: hippocampus; intraoperative hypothermia; postoperative cognitive dysfunction; synaptic plasticity; synaptic plasticity-related protein.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Study design to evaluate the effects of intraoperative hypothermia on postoperative cognitive function in rats. (A) Schematic timeline of the experimental procedure; (B) representative image of Y-maze apparatus; (C) representative graph of the MWM apparatus.
Figure 2
Figure 2
The effects of intraoperative hypothermia on the spatial working memory of rats measured by the Y-maze spontaneous alternation. (A) Representative mobile trajectories of rats among different groups; (B) the number of total arm entries of rats from different groups; (C) the total distance moved during 8 min free exploration in the Y-maze; (D) the spontaneous alternation percentage in different groups. Data are expressed as mean ± SEM. * p < 0.05, n = 9–10.
Figure 3
Figure 3
The effects of intraoperative hypothermia on spatial learning and memory of rats were determined by the MWM. (A) The representative swimming trajectories of rats from each group on the last day of training trials; (B) the representative swimming paths of rats from each group in the probe test; (C) the average swimming speeds of rats in different groups on successive MWM training days; (D) the average escape latencies to find the hidden platform across three trials on four consecutive training days; (E) the time spent in the target quadrant in the probe test; (F) the number of platform crossings during the probe test. Data are expressed as mean ± SEM. * p < 0.05, ** p < 0.01 and *** p < 0.001, n = 9–10.
Figure 4
Figure 4
Morphological changes of hippocampal neurons in rats among groups were observed under bright-field illumination using a fluorescence microscopy imaging system. (A–C) Representative images of HE staining in hippocampal slices; (D) quantitative analysis of injured neurons with neuronal pyknosis and necrosis in the hippocampal DG region. The white arrow indicates a disorderly nucleus, neuronal pyknosis and necrosis. Magnification: ×40; scale bar: 50 µm. Data are expressed as mean ± SEM. * p < 0.05, n = 4.
Figure 5
Figure 5
Expression levels of hippocampal synaptic plasticity-related proteins in rats and the effects of intraoperative hypothermia. (A) The visualisation of protein bands of CREB, p-CREB (S133), Arc, AMPAR1, p-AMPAR1 (S831), and β-actin; (B) quantitative analysis of CREB expression levels normalised to β-actin band intensities; (C) quantitative analysis of p-CREB (S133) expression levels normalised to CREB band intensities; (D) quantitative analysis of Arc expression levels normalised to β-actin band intensities; (E) quantitative analysis of AMPAR1 expression levels normalised to β-actin band intensities; (F) quantitative analysis of p-AMPAR1 (S831) expression levels normalised to AMPAR1 band intensities. Data are expressed as mean ± SEM. * p < 0.05, ** p < 0.01 and *** p < 0.001, n = 3–4.

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