Effect of Adenosine Receptor Agonist and Ascorbic Acid on Ultrastructure of Hippocampal CA1 Neurons after Ischemia-Reperfusion Injury

Document Type : Original Article (s)

Authors

1 Assistant Professor, Department of Anatomy, School of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

2 Associate Professor, Cellular and Molecular Research Center AND Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

3 Assistant Professor, Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran

4 Associate Professor, Department of Anatomy, School of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

Abstract

Background: In brain ischemia, blood and oxygen supply decrease and after reperfusion, free radicals and reactive oxygen species (ROS) cause severe damage. As hippocampal injury after ischemia-reperfusion causes some complications, in this study we analyzed the effect of adenosine receptor agonist (N6-cyclopentyladenosine or CPA) and ascorbic acid on ultrastructure of hippocampal CA1 neurons after ischemia-reperfusion.Methods: 35 male rats in 5 groups were used. Ischemia-reperfusion performed by occlusion of common carotids for 15 minutes. CPA and ascorbic acids were intraperitoneally injected for 7 days after ischemia, and 2 weeks before and for 7 days after ischemia, respectively. After 20 days, brain samples were isolated, prepared, and assayed using transmission electron microscopy (TEM).Findings: Ultrastructure assay of hippocampal CA1 neurons after ischemia-reperfusion with transmission electron microscopy showed recovery of intracellular organelles particularly mitochondria of treated groups. In combination therapy, these improvements were better.Conclusion: Intraperitoneal injection of CPA and ascorbic acid after ischemia-reperfusion can reduce neural damage in CA1 region of hippocampus.

Keywords

References

  1. Lee JM, Grabb MC, Zipfel GJ, Choi DW. Brain tissue responses to ischemia. J Clin Invest 2000; 106(6): 723-31.
  2. Dawson TM, Dawson VL, Snyder SH. A novel neuronal messenger molecule in brain: the free radical, nitric oxide. Ann Neurol 1992; 32(3): 297-311.
  3. Camarata PJ, Heros RC, Latchaw RE. "Brain attack": the rationale for treating stroke as a medical emergency. Neurosurgery 1994; 34(1): 144-57.
  4. Eichenbaum H. Hippocampus: cognitive processes and neural representations that underlie declarative memory. Neuron 2004; 44(1): 109-20.
  5. Buttner-Ennever J. The rat brain in stereotaxic coordinates. J Anat 1997; 191(Pt 2): 315–7.
  6. Taupin P. The hippocampus: Neurotransmission and plasticity in the nervous System. New York, NY: Nova Biomedical Books; 2008.
  7. Vollert C, Forkuo GS, Bond RA, Eriksen JL. Chronic treatment with DCPCX, an adenosine A(1) antagonist, worsens long-term memory. Neurosci Lett 2013; 548: 296-300.
  8. Johansson B, Halldner L, Dunwiddie TV, Masino SA, Poelchen W, Gimenez-Llort L, et al. Hyperalgesia, anxiety, and decreased hypoxic neuroprotection in mice lacking the adenosine A1 receptor. Proc Natl Acad Sci USA 2001; 98(16): 9407-12.
  9. Modlinger PS, Welch WJ. Adenosine A1 receptor antagonists and the kidney. Curr Opin Nephrol Hypertens 2003; 12(5): 497-502.
  10. Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Ischemia/Reperfusion. Compr Physiol 2016; 7(1): 113-70.
  11. Sai K, Yang D, Yamamoto H, Fujikawa H, Yamamoto S, Nagata T, et al. A(1) adenosine receptor signal and AMPK involving caspase-9/-3 activation are responsible for adenosine-induced RCR-1 astrocytoma cell death. Neurotoxicology 2006; 27(4): 458-67.
  12. Zamani M, Soleimani M, Golab F, Mohamadzadeh F, Mehdizadeh M, Katebi M. NeuroProtective effects of adenosine receptor agonist coadministration with ascorbic acid on CA1 hippocampus in a mouse model of ischemia reperfusion injury. Metab Brain Dis 2013; 28(3): 367-74.
  13. Wilson MK, Baguley BC, Wall C, Jameson MB, Findlay MP. Review of high-dose intravenous vitamin C as an anticancer agent. Asia Pac J Clin Oncol 2014; 10(1): 22-37.
  14. Hossein Hassanshahi G, Hassanshahi J, Zamani M, Hakimizadeh E, Soleimani M. Comparison of therapeutic effects of vitamin c and coq10 in reducing of damaged cells in mice hippocampus following ischemia-reperfusion. J Mazandaran Univ Med Sci. 2012; 22 (94): 2-13. [In Persian].
  15. Melani A, Pugliese AM, Pedata F. Adenosine receptors in cerebral ischemia. Int Rev Neurobiol 2014; 119: 309-48.
  16. Shugalei I. Features of vitamin C metabolism and the functional status of the liver in alcoholism and alcoholic delirium in the stage of detoxification therapy. Zh Nevropatol Psikhiatr Im S S Korsakova 1987; 87(2): 240-3. [In Russian].
  17. Stafford A. Potentiation of adenosine and the adenine nucleotides by dipyridamole. Br J Pharmacol Chemother 1966; 28(2): 218-27.
  18. Zarch AV, Toroudi HP, Soleimani M, Bakhtiarian A, Katebi M, Djahanguiri B. Neuroprotective effects of diazoxide and its antagonism by glibenclamide in pyramidal neurons of rat hippocampus subjected to ischemia-reperfusion-induced injury. Int J Neurosci 2009; 119(9): 1346-61.
  19. Schmidt W, Reymann KG. Proliferating cells differentiate into neurons in the hippocampal CA1 region of gerbils after global cerebral ischemia. Neurosci Lett 2002; 334(3): 153-6.
  20. Niwano Y, Saito K, Yoshizaki F, Kohno M, Ozawa T. Extensive screening for herbal extracts with potent antioxidant properties. J Clin Biochem Nutr 2011; 48(1): 78-84.
  21. Miura S, Ishida-Nakajima W, Ishida A, Kawamura M, Ohmura A, Oguma R, et al. Ascorbic acid protects the newborn rat brain from hypoxic-ischemia. Brain Dev 2009; 31(4): 307-17.
  22. Frei B, England L, Ames BN. Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci USA 1989; 86(16): 6377-81.
  23. Cotter MA, Love A, Watt MJ, Cameron NE, Dines KC. Effects of natural free radical scavengers on peripheral nerve and neurovascular function in diabetic rats. Diabetologia 1995; 38(11): 1285-94.
  24. O'Neill MJ, Hicks CA, Ward MA, Osborne DJ, Wishart G, Mathews KS, et al. LY393615, a novel neuronal Ca(2+) and Na(+) channel blocker with neuroprotective effects in models of in vitro and in vivo cerebral ischemia. Brain Res 2001; 888(1): 138-49.
  25. Joshi VK, Sharma SK. Comparative fermentation behaviour, physico-chemical and sensory characteristics of plum wine as effected by type of preservative. Chemie, Mikrobiologie, Technologie der Lebensmittel 1995; 17(3-4): 65-73.
  26. Zamani M, Katebi M, Mehdizadeh M, Kafami L, Soleimani M. Combination therapy with A1 receptor agonist and vitamin C improved working memory in a mouse model of global ischemia-reperfusion. Basic Clin Neurosci 2013; 4(2): 111-6.
Journal of Isfahan Medical School
Volume 35, Issue 439 - Serial Number 439
May and June 2017
Pages 862-869

Files

History

  • Receive Date: 16 May 2017
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics