Skip to main content
Log in

Ulinastatin Alleviates Neuroinflammation but Fails to Improve Cognitive Function in Aged Rats Following Partial Hepatectomy

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Postoperative cognitive dysfunction (POCD) is very common complication of surgery in aged individuals. Accumulated evidence suggests that neuroinflammation may be the underlying cause of POCD. The aim of the present study was to investigate the effects of ulinastatin (UTI) on neuroinflammation and on learning and memory of aged rats after anesthesia and surgery. Our results showed that anesthetic isoflurane increased the hippocampal mRNA level of IL-1β, while surgery of partial hepatectomy increased the hippocampal mRNA levels of IL-1β, TNF-α, and IL-6 as well as impaired rats’ spatial memory at day 7 post-surgery. UTI (10,000 U/kg, i.v.) decreased the anesthesia- and surgery-induced increases in mRNA levels of all three cytokines, but did not improve the rats’ impaired working memory. In conclusion, moderate and temporary suppression of UTI-induced inflammatory cytokines in hippocampus is not sufficient to alleviate the impairment of working memory.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Dijkstra JB, Houx PJ, Jolles J (1999) Cognition after major surgery in the elderly: test performance and complaints. Br J Anaesth 82:867–874

    Article  PubMed  CAS  Google Scholar 

  2. Steinmetz J, Christensen KB, Lund T, Lohse N, Rasmussen LS (2009) Long-term consequences of postoperative cognitive dysfunction. Anesthesiology 110:548–555

    Article  PubMed  Google Scholar 

  3. Rosczyk HA, Sparkman NL, Johnson RW (2008) Neuroinflammation and cognitive function in aged mice following minor surgery. Exp Gerontol 43:840–846

    Article  PubMed  CAS  Google Scholar 

  4. Newman S, Stygall J, Hirani S, Shaefi S, Maze M (2007) Postoperative cognitive dysfunction after noncardiac surgery: a systematic review. Anesthesiology 106:572–590

    Article  PubMed  Google Scholar 

  5. Canet J, Raeder J, Rasmussen LS, Enlund M, Kuipers HM, Hanning CD, Jolles J, Korttila K, Siersma VD, Dodds C, Abildstrom H, Sneyd JR, Vila P, Johnson T, Munoz Corsini L, Silverstein JH, Nielsen IK, Moller JT (2003) Cognitive dysfunction after minor surgery in the elderly. Acta Anaesthesiol Scand 47:1204–1210

    Article  PubMed  CAS  Google Scholar 

  6. Terrando N, Eriksson LI, Kyu Ryu J, Yang T, Monaco C, Feldmann M, Jonsson Fagerlund M, Charo IF, Akassoglou K, Maze M (2011) Resolving postoperative neuroinflammation and cognitive decline. Ann Neurol 70:986–995

    Article  PubMed  CAS  Google Scholar 

  7. Cibelli M, Fidalgo AR, Terrando N, Ma D, Monaco C, Feldmann M, Takata M, Lever IJ, Nanchahal J, Fanselow MS, Maze M (2010) Role of interleukin-1beta in postoperative cognitive dysfunction. Ann Neuro 168:360–368

    Article  Google Scholar 

  8. Terrando N, Monaco C, Ma D, Foxwell BM, Feldmann M, Maze M (2010) Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci USA 107:20518–20522

    Article  PubMed  CAS  Google Scholar 

  9. Cao XZ, Ma H, Wang JK, Liu F, Wu BY, Tian AY, Wang LL, Tan WF (2010) Postoperative cognitive deficits and neuroinflammation in the hippocampus triggered by surgical trauma are exacerbated in aged rats. Prog Neuropsychopharmacol Biol Psychiatry 34:1426–1432

    Article  PubMed  CAS  Google Scholar 

  10. Fang Y, Xu P, Gu C, Wang Y, Fu XJ, Yu WR, Yao M (2011) Ulinastatin improves pulmonary function in severe burn-induced acute lung injury by attenuating inflammatory response. J Trauma 71:1297–1304

    Article  PubMed  Google Scholar 

  11. Park KH, Lee KH, Kim H, Hwang SO (2010) The anti-inflammatory effects of ulinastatin in trauma patients with hemorrhagic shock. J Korean Med Sci 25:128–134

    Article  PubMed  CAS  Google Scholar 

  12. Tsujino T, Komatsu Y, Isayama H, Hirano K, Sasahira N, Yamamoto N, Toda N, Ito Y, Nakai Y, Tada M, Matsumura M, Yoshida H, Kawabe T, Shiratori Y, Omata M (2005) Ulinastatin for pancreatitis after endoscopic retrograde cholangiopancreatography: a randomized, controlled trial. Clin Gastroenterol Hepatol 3:376–383

    Article  PubMed  CAS  Google Scholar 

  13. Yano T, Anraku S, Nakayama R, Ushijima K (2003) Neuroprotective effect of urinary trypsin inhibitor against focal cerebral ischemia-reperfusion injury in rats. Anesthesiology 98:465–473

    Article  PubMed  CAS  Google Scholar 

  14. Iwama H, Ohmori S, Tsutsumi T (2000) Detectable concentrations of urinary trypsin inhibitor in cerebrospinal fluid. J Neurosurg Anesthesiol 12:29–32

    Article  PubMed  CAS  Google Scholar 

  15. Kamer AR, Galoyan SM, Haile M, Kline R, Boutajangout A, Li YS, Bekker A (2012) Meloxicam improves object recognition memory and modulates glial activation after splenectomy in mice. Eur J Anaesthesiol 29:332–337

    Article  PubMed  CAS  Google Scholar 

  16. He HJ, Wang Y, Le Y, Duan KM, Yan XB, Liao Q, Liao Y, Tong JB, Terrando N, Ouyang W (2012) Surgery upregulates high mobility group box-1 and disrupts the blood-brain barrier causing cognitive dysfunction in aged rats. CNS Neurosci Ther 18:994–1002

    Article  PubMed  CAS  Google Scholar 

  17. Wuri G, Wang DX, Zhou Y, Zhu SN (2011) Effects of surgical stress on long-term memory function in mice of different ages. Acta Anaesthesiol Scand 55:474–485

    Article  PubMed  CAS  Google Scholar 

  18. Peng M, Wang YL, Wang FF, Chen C, Wang CY (2012) The cyclooxygenase-2 inhibitor parecoxib inhibits surgery-induced proinflammatory cytokine expression in the hippocampus in aged rats. J Surg Res 178:e1–e8

    Article  PubMed  CAS  Google Scholar 

  19. Tanaka H, Hashizume K, Enosawa S, Suzuki S (2003) Successful transplantation of a 20 % partial liver graft in rats: a technical innovation. J Surg Res 110:409–412

    Article  PubMed  Google Scholar 

  20. Vorhees CV, Williams MT (2006) Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc 1:848–858

    Article  PubMed  Google Scholar 

  21. Boost KA, Hofstetter C, Flondor M, Betz C, Homann M, Pfeilschifter J, Muehl H, Zwissler B (2006) Desflurane differentially affects the release of proinflammatory cytokines in plasma and bronchoalveolar fluid of endotoxemic rats. Int J Mol Med 17:1139–1144

    PubMed  CAS  Google Scholar 

  22. Carlson NG, Wieggel WA, Chen J (1999) Inflammatory cytokines IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha impart neuroprotection to an excitotoxin through distinct pathways. J Immunol 163:3963–3968

    PubMed  CAS  Google Scholar 

  23. Bingyang J, Jinping L, Mingzheng L, Guyan W, Zhengyi F (2007) Effects of urinary protease inhibitor on inflammatory response during on-pump coronary revascularisation. J Cardiovasc Surg (Torino) 48:497–503

    CAS  Google Scholar 

  24. Steinman L (2010) Modulation of postoperative cognitive decline via blockade of inflammatory cytokines outside the brain. Proc Natl Acad Sci USA 107:20595–20596

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

The Author(s) declare(s) that they have no conflicts of interest to disclose.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Pan Ning-ling.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, M., Yong-zhe, L., Ya-qun, M. et al. Ulinastatin Alleviates Neuroinflammation but Fails to Improve Cognitive Function in Aged Rats Following Partial Hepatectomy. Neurochem Res 38, 1070–1077 (2013). https://doi.org/10.1007/s11064-013-1018-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-013-1018-z

Keywords

Navigation