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The Choice of General Anesthetics May Not Affect Neuroinflammation and Impairment of Learning and Memory After Surgery in Elderly Rats

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Abstract

Postoperative cognitive dysfunction (POCD) often occurs in elderly patients and may involve neuroinflammation. This study was to determine whether anesthetic choice (intravenous vs. volatile anesthetics) affects cognitive impairment and neuroinflammation in elderly rat. Total 54 twenty-month old male Fischer 344 rats were assigned randomly to control, right carotid exposure under propofol-buprenorphine or isoflurane-buprenorphine anesthesia groups. They were tested by Barnes maze and fear conditioning from 6 days after the surgery. Their brains were harvested 24 h after the surgery for quantifying interleukin (IL) 1β, tumor necrosis factor (TNF)α and ionized calcium binding adaptor molecule 1 (Iba-1). We showed that the heart rates and mean arterial blood pressure were similar during surgery under propofol-buprenorphine or isoflurane-buprenorphine anesthesia. There was no difference in the surgery-induced increase of the plasma IL-1β and TNFα levels under these two types of anesthesia. Rats subjected to surgery took longer than control rats to identify the target hole 8 days after the completion of training sessions in Barnes maze [32 ± 23 s for control, 118 ± 64 s for propofol group (P < 0.05 vs. control), 107 ± 64 s for isoflurane group (P < 0.05 vs. control)] and had less freezing behavior in the fear conditioning test. Surgery and anesthesia increased IL-1β and Iba-1 but did not affect tau phosphorylated at S199/202 and S396 in the cerebral cortex and hippocampus. Our results suggest that surgery under general anesthesia induces neuroinflammation and cognitive impairment. Anesthetic choice may not be a significant modifiable factor for these effects.

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Abbreviations

ACTH:

Adrenocorticotropic hormone

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

Iba-1:

Ionized calcium binding adaptor molecule 1

IL:

Interleukin

MAP:

Mean arterial blood pressure

POCD:

Postoperative cognitive dysfunction

TNFα:

Tumor necrosis factor α

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Grant Support

This study was supported by grants (R01 GM065211 and R01 GM098308 to Z Zuo) from the National Institutes of Health, Bethesda, MD, by a grant from the International Anesthesia Research Society (2007 Frontiers in Anesthesia Research Award to Z Zuo), Cleveland, OH, by a Grant-in-Aid from the American Heart Association Mid-Atlantic Affiliate (10GRNT3900019 to Z Zuo), Baltimore, MD, and the Robert M. Epstein Professorship endowment, University of Virginia, Charlottesville, VA.

Disclosure/Conflict of Interest

The authors declare no other financial supports for this study except for those grants stated above from funding agencies for non-profit. The authors also declare no conflict of interest in the content of this study.

Authors’ Contribution

ZZ conceived the concept of the project. JZ, HT, WJ and ZZ designed the experiments. JZ and HT performed experiments with the help of Jackie Washington, a technician in Dr. Zuo’s laboratory. JZ and HT performed initial data analysis. ZZ did the final data analysis. JZ drafted the Methods section. ZZ revised the Methods section and wrote the other parts of the manuscript.

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    Authors and Affiliations

    1. Department of Anesthesiology, University of Virginia, Charlottesville, VA, USA

      Junfeng Zhang, Hongying Tan & Zhiyi Zuo

    2. Department of Anesthesiology, Shanghai 6th People’s Hospital, Shanghai Jiaotong University, 600 Yishan Road, Shanghai, 200233, China

      Junfeng Zhang & Wei Jiang

    3. Department of Anesthesiology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, China

      Hongying Tan

    4. Department of Anesthesiology, University of Virginia Health System, 1 Hospital Drive, PO Box 800710, Charlottesville, VA, 22908-0710, USA

      Zhiyi Zuo

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    1. Junfeng Zhang
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    Correspondence to Wei Jiang or Zhiyi Zuo.

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    Junfeng Zhang and Hongying Tan contributed equally to this study.

    The research work was performed in, and should be attributed to, the Department of Anesthesiology, University of Virginia, Charlottesville, VA 22908, U.S.A.

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    Zhang, J., Tan, H., Jiang, W. et al. The Choice of General Anesthetics May Not Affect Neuroinflammation and Impairment of Learning and Memory After Surgery in Elderly Rats. J Neuroimmune Pharmacol 10, 179–189 (2015). https://doi.org/10.1007/s11481-014-9580-y

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