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27 February 2019 : Laboratory Research

A Mouse Model of Hepatic Ischemia-Reperfusion Injury Demonstrates Potentially Reversible Effects on Hippocampal Neurons and Postoperative Cognitive Function

Weiwei Wu12BD, Yan Wu3EG, Gao Cheng2DF, Chi Zhang4AE, Hongxian Wang1BF, Yuanhai Li1AC*

DOI: 10.12659/MSM.912658

Med Sci Monit 2019; 25:1526-1536

Abstract

BACKGROUND: 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

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750