A Mouse Model of Hepatic Ischemia-Reperfusion Injury Demonstrates Potentially Reversible Effects on Hippocampal Neurons and Postoperative Cognitive Function
Weiwei Wu, Yan Wu, Gao Cheng, Chi Zhang, Hongxian Wang, Yuanhai Li
Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China (mainland)
Med Sci Monit 2019; 25:1526-1536
This study aimed to investigate cognitive function, hippocampal neuronal changes, and the expression of inflammatory cytokines in a mouse model of hepatic ischemia-reperfusion injury.
MATERIAL AND METHODS: Sixty mice were divided into the sham group, which underwent surgery without vascular occlusion; the I/R1 group, with occlusion of the left hepatic artery and portal vein for 20 min, and reperfusion for 30 min; and the I/R2 group, with occlusion of the left hepatic artery and portal vein for 40 min, and reperfusion for 30 min. At postoperative day 4 and 11, ten mice from each group underwent the Morris water maze (MWM) task. Hippocampal tissues were stained for Nissl bodies. Expression of nuclear factor-κB (NF-κB) and choline acetyltransferase (ChAT) were quantified by immunohistochemistry. Serum tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured by enzyme-linked immunosorbent assay (ELISA).
RESULTS: Groups I/R1 and I/R2 showed a significantly increased latency in the MWM test between days 5–9, compared with the sham group (P<0.05), with no difference by day 11; the I/R2 group had an initial lower crossing frequency (P<0.05), with no difference by day 18. The I/R2 group showed reduced numbers of Nissl bodies in hippocampal neurons. The I/R1 and I/R2 groups had increased expression of NF-κB, TNF-α, and IL-1β and decreased ChAT. No differences between the groups were found in levels of NF-κB, TNF-α, IL-1β, or ChAT by day 18.
CONCLUSIONS: A mouse model of hepatic ischemia-reperfusion injury showed transient and reversible cognitive dysfunction, changes in hippocampal neurons, and expression of inflammatory cytokines.
Keywords: Cognitive Science, Hippocampus, Reperfusion