Effects of Hydrogen-Rich Saline on Hepatectomy-Induced Postoperative Cognitive Dysfunction in Old Mice

Abstract

This study aims to investigate the protective effects and underlying mechanisms of hydrogen-rich saline on the cognitive functions of elder mice with partial hepatectomy-induced postoperative cognitive dysfunction (POCD). Ninety-six old male Kunming mice were randomly divided into 4 groups (n = 24 each): control group (group C), hydrogen-rich saline group (group H), POCD group (group P), and POCD + hydrogen-rich saline group (group PH). Cognitive function was subsequently assessed using Morris water-maze (MWM) test. TNF-α and IL-1β levels were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, along with NF-κB activity determined by ELISA. The morphology of hippocampal tissues were further observed by HE staining. Learning and memory abilities of mice were significantly impaired at day 10 and day 14 post-surgery, as partial hepatectomy significantly prolonged the escape latency, decreased time at the original platform quadrant and frequency of crossing in group P when compared to group C (p < 0.05). The surgery also increased the contents of TNF-α, IL-1β, and NF-κB activity at all time points after surgery (p < 0.05). The introduction of hydrogen-rich saline (group PH) partially rescued spatial memory and learning as it shortened escape latency and increased time and crossing frequency of original platform compared to group P (p < 0.05). Moreover, such treatment also decreased TNF-α and IL-1β levels and NF-κB activity (p < 0.05). In addition, cell necrosis in the hippocampus induced by hepatectomy was also rescued by hydrogen-rich saline. Hydrogen-rich saline can alleviate POCD via inhibiting NF-κB activity in the hippocampus and reducing inflammatory response.

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Acknowledgments

This work was supported by grants from the Shengjing Hospital of China Medical University Foundation (Funding NO. 2014sj08) and National Natural Science Foundation (Funding NO. 81473285).

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Correspondence to Ping Zhao.

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Animal experiments were performed in accordance with Guidelines for the Care and Use of Laboratory Animals stipulated by the Ethics Committee of the Shengjing Hospital Affiliated of China Medical University.

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ESM 1

Fig. S1 Representative swimming traces of mice during MWM test in each group at day 8, day 10, and day 14 after surgery; group C, control group without surgery; group H, hydrogen-rich saline treated without surgery; group P, hepatectomy only; group PH, surgery plus hydrogen-rich saline treatment from day 8 to day 14 post-surgery. (TIF 997 kb)

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Tian, Y., Guo, S., Zhang, Y. et al. Effects of Hydrogen-Rich Saline on Hepatectomy-Induced Postoperative Cognitive Dysfunction in Old Mice. Mol Neurobiol 54, 2579–2584 (2017). https://doi.org/10.1007/s12035-016-9825-2

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Keywords

  • Hydrogen-rich saline
  • POCD
  • NF-κB
  • Inflammatory response