Skip to main content
SpringerLink
Log in

Effects of calpain on sevoflurane-induced aged rats hippocampal neuronal apoptosis

  • Original Article
  • Published:
Aging Clinical and Experimental Research Aims and scope Submit manuscript

Abstract

Background

Sevoflurane is one of the most commonly used volatile anesthetics and it has been shown to induce widespread apoptotic neurodegeneration in aged rat. Calpain is also activated during apoptosis in several types of cells. We hypothesized that calpain resulted in apoptosis under long time sevoflurane exposure, and it might play a role in the sevoflurane-induced memory impairment in aged rats.

Methods

Seventy-two 18-month-old male Sprague–Dawley rats were randomly divided into three groups (n = 24): Control group rats were exposed to simply humid 50 % O2 balanced by N2 for 3 h; While M group rats received calpain inhibitor 10 mg/kg via the tail vein intravenously at 30 min before the animals inhaled 3 % sevoflurane for 3 h, subsequently received MDL 28170 3.33 mg/kg/h for 3 h. Sev group rats were only exposed to 3 % sevoflurane for 3 h without calpain inhibitor. Morris Water Maze was used to test the ability of learning and memory. Cytosolic calcium concentration was measured by using flow cytometry. Annexin-V labeled with a fluorophore or biotin can identify apoptotic cells by binding to PS. The expression of calpain in the hippocampus of rats was tested by Western blots.

Results

The results showed that the M group had a shorter latency and had a larger number of times crossing over the previous platform site than that of the Sev group. Compared with Sev group, apoptosis rate and 76/80 kDa ratio of μ-calpain were significantly decreased in M group on the 1st day.

Conclusions

Sevoflurane might induce apoptosis through increasing [Ca2+]c and the activity of μ-calpain, which might be identified at least partially the molecular mechanism by which sevoflurane induces apoptosis.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Parikh SS, Chung F (1995) Postoperative delirium in the elderly. Anesth Analg 80:1223–1232

    CAS  PubMed  Google Scholar 

  2. Vacas S, Degos V, Feng X et al (2013) The neuroinflammatory response of postoperative cognitive decline. Br Med Bull 106:161–178

    Article  CAS  PubMed  Google Scholar 

  3. McLay RN, Freeman SM, Harlan RE et al (1997) Aging in the hippocampus: interrelated actions of neurotrophins and glucocorticoids. Neurosci Behav Rev 21:615–629

    Article  CAS  Google Scholar 

  4. Liu XS, Xue QS, Zeng QW et al (2010) Sevoflurane impairs memory consolidation in rats, possibly through inhibiting phosphorylation of glycogen synthase kinase-3beta in the hippocampus. Neurobiol Learn Mem 94:461–467

    Article  CAS  PubMed  Google Scholar 

  5. Culley DJ, Xie Z, Crosby G (2007) General anesthetic-induced neurotoxicity: an emerging problem for the young and old? Curr Opin Anaesthesiol 20:408–413

    Article  PubMed  Google Scholar 

  6. Hudson AE, Hemmings HC Jr (2011) Are anaesthetics toxic to the brain? Br J Anaesth 107:30–37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Perouansky M (2008) General anesthetics and long-term neurotoxicity. Handb Exp Pharmacol 182:143–157

  8. Alkire MT, Gruver R, Miller J et al (2008) Neuroimaging analysis of an anesthetic gas that blocks human emotional memory. Proc Natl Acad Sci USA 105:1722–1727

    Article  PubMed  PubMed Central  Google Scholar 

  9. Wiklund A, Granon S, Faure P et al (2009) Object memory in young and aged mice after sevoflurane anaesthesia. NeuroReport 20:1419–1423

    Article  CAS  PubMed  Google Scholar 

  10. Vanags DM, PormAres MI, Coppola S et al (1996) Protease involvement in fodrin cleavage and phosphatidyl- serine exposure in apoptosis. J Biol Chem 271:31075–31085

    Article  CAS  PubMed  Google Scholar 

  11. Zimmerman UJP, Schlaepfer WW (1991) Two stage autolysis of the catalytic subunit initiates activation of calpain. Biochim Biophys Acta 1078:192–198

    Article  CAS  PubMed  Google Scholar 

  12. Neumar RW, Hagle SM, DeGracia DJ et al (1996) Brain μ-calpain autolysis during global cerebral ischemia. J Neurochem 66:421–424

    Article  CAS  PubMed  Google Scholar 

  13. Ostwald K, Hayashi M, Nakamura M et al (1994) Subcellular distribution of calpain and calpastatin immunoreactivity and fodrin proteolysis in rabbit hippocampus after hypoxia and glucocorticoid treatment. J Neurochem 63:1069–1076

    Article  CAS  PubMed  Google Scholar 

  14. Markgraf CG, Velayo NL, Johnson MP et al (1998) Six-hour window of opportunity for calpain inhibition in focal cerebral ischemia in rats. Stroke 29:152–158

    Article  CAS  PubMed  Google Scholar 

  15. Ishida A, Trescher WH, Lange MS et al (2001) Prolonged suppression of brain nitric oxide synthase activity by 7-nitroindazole protects against cerebral hypoxic–ischemic injury in neonatal rat. Brain Dev 23:349–354

    Article  CAS  PubMed  Google Scholar 

  16. Satomoto M, Satoh Y, Terui K et al (2009) Neonatal exposure to sevoflurane induces abnormal social behaviors and deficits in fear conditioning in mice. Anesthesiology 110:628–637

    Article  CAS  PubMed  Google Scholar 

  17. Gupta S (2001) Molecular steps of death receptor and mitochondrial pathways of apoptosis. Life Sci 69:2957–2964

    Article  CAS  PubMed  Google Scholar 

  18. Chen G, Gong M, Yan M et al (2013) Sevoflurane induces endoplasmic reticulum stress mediated apoptosis inhippocampal neurons of aging rats. PLoS One 8:e57870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Matus S, Glimcher LH, Hetz C (2011) Protein folding stress in neurodegenerative diseases: a glimpse into the ER. Curr Opin Cell Biol 23:239–252

    Article  CAS  PubMed  Google Scholar 

  20. Wang QJ, Li KZ, Yao SL (2008) Effect of inhalational anesthetics on cytotoxicity and intracellular calcium differently in rat pheochromocytoma cells (PC 12). J Huazhong Univ Sci Technol [Med Sci] 28:104–109

  21. Nathb R, Raser KJ, Stafford D et al (1996) Nonerythroid alpha-spectrin breakdown by calpain and interleukin 1 betaconverting- enzyme-like protease(s) in apoptotic cells: contributory roles of both protease families in neuronal apoptosis. Biochem J 319:683–690

  22. O’Hanlon GM, Humphreys PD, Goldman RS et al (2003) Calpain inhibitors protect against axonal degeneration in a model of anti-ganglioside antibody-mediated motor nerve terminal injury. Brain 126:2497–2509

    Article  PubMed  Google Scholar 

  23. Hong SC, Goto Y, Lanzino G et al (1994) Neuroprotection with a calpain inhibitor in a model of focal cerebral ischemia. Stroke 25:663–669

    Article  CAS  PubMed  Google Scholar 

  24. Hiramatsu K, Kassell NF, Lee KS (1993) Improved posthypoxic recovery of synaptic transmission in gerbil neocortical slices treated with a calpain inhibitor. Stroke 24:1725–1728

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by departments Funding (National Natural Science Foundation and Hebei Province Science and Technology Support Project) and institutions involved and grants from The third hospital, Hebei Medical University.

Author information

Authors and Affiliations

  1. Department of Anesthesiology, The Third Hospital of Hebei Medical University, No. 139 ZiQiang Road, Shi Jiazhuang, 050051, China

    Xiang Liu, Xueyin Song, Tianbao Yuan, Jihua He, Xiuli Wang & Qiujun Wang

Authors
  1. Xiang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xueyin Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tianbao Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jihua He
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiuli Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qiujun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qiujun Wang.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Statement of human and animal rights

We solemnly declare there is no harm to animals of fundamental rights.

Informed consent

All institutional and national guidelines for the care and use of laboratory animals were followed.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, X., Song, X., Yuan, T. et al. Effects of calpain on sevoflurane-induced aged rats hippocampal neuronal apoptosis. Aging Clin Exp Res 28, 633–639 (2016). https://doi.org/10.1007/s40520-015-0466-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40520-015-0466-5

Keywords

Search

Navigation