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Comparative Study of the Intensity of Nitric Oxide Production and Copper Content in Hippocampus of Rats After Modeling of Hemorrhagic Stroke and Brain Injury

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Abstract

A comparative experimental analysis of intensity of nitric oxide (NO) production and the copper content in the tissues of hippocampus of male Wistar rats after modeling of hemorrhagic stroke and brain injury was conducted using EPR spectroscopy. Modeling of hemorrhagic stroke was carried out by microinjection of 500 nl of autologous blood into the brain to a depth of 5.0 mm (hippocampus) on the left side. Brain injury was performed by removing a piece of nerve tissue from 5.0 mm depth on the left side of hippocampus. It was registered a significant decrease in the NO content in hippocampus by 36 ± 17% on the 3rd day after modeling of hemorrhagic stroke together with decrease by an average of 24 ± 14% of the copper content. There were no significant changes in the NO level in hippocampus found neither on the 3rd day nor on the 7th day after brain injury modeling. There was also no change in copper content. Thus, it was experimentally demonstrated that modeling of brain injury, in contrast to hypoxia induced by hemorrhagic stroke, was not accompanied with significant changes in NO production in hippocampus of rat.

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References

  1. H.A. Beydoun, C. Butt, M.A. Beydoun, S. Hossain, S.M. Eid, A.B. Zonderman, Cross-sectional study of major procedure codes among hospitalized patients with traumatic brain injury by level of injury severity in the 2004 to 2014 Nationwide Inpatient Sample. Medicine (Baltimore) 100(6), e24438 (2021). https://doi.org/10.1097/MD.0000000000024438

    Article  Google Scholar 

  2. S.T. Dawodu, Traumatic Brain Injury (TBI) Definition, Epidemiology, Pathophysiology (Medscape, New York, 2015)

    Google Scholar 

  3. M. Galgano, G. Toshkezi, X. Qiu, T. Russell, L. Chin, L.-R. Zhao, Traumatic brain injury: current treatment strategies and future endeavors. Cell Transpl. 26(7), 1118–1130 (2017). https://doi.org/10.1177/0963689717714102

    Article  Google Scholar 

  4. J.P. Bolanos, A. Almeida, Roles of nitric oxide in brain hypoxia-ischemia. Biochim. Biophys. Acta 1411, 415–436 (1999)

    Article  Google Scholar 

  5. H.M. Bramlett, W.D. Dietrich, Pathophysiology of cerebral ischemia and brain trauma: similarities and differences. J. Cereb. Blood Flow Metab. 24(2), 133–150 (2004). https://doi.org/10.1097/01.WCB.0000111614.19196.04

    Article  Google Scholar 

  6. J. Serrano, A.P. Fernández, R. Martínez-Murillo, D. Alonso, J. Rodrigo, E. Salas, M. Mourelle, A. Martínez, The nitric oxide donor LA 419 decreases ischemic brain damage. Int. J. Mol. Med. 19(2), 229–236 (2007). https://doi.org/10.3892/ijmm.19.2.229

    Article  Google Scholar 

  7. P. Pacher, J.S. Beckman, L. Liaudet, Nitric oxide and peroxynitrite in health and disease. Physiol. Rev 87, 315–427 (2007). https://doi.org/10.1152/physrev.00029.2006

    Article  Google Scholar 

  8. V. Calabrese, C. Mancuso, M. Calvani, E. Rizzarelli, D.A. Butterfield, A.M.G. Stella, Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity. Nat. Rev. Neurosci. 8, 767–775 (2007). https://doi.org/10.1038/nrn2214

    Article  Google Scholar 

  9. Kh.L. Gainutdinov, S.A. Gavrilova, V.S. Iyudin, A.V. Golubeva, M.P. Davydova, G.G. Jafarova, V.V. Andrianov, V.B. Koshelev, EPR study of the intensity of the nitric oxide production in rat brain after ischemic stroke. Appl. Magn. Reson. 40, 267–278 (2011)

    Article  Google Scholar 

  10. P.S. Garry, M. Ezra, M.J. Rowland, J. Westbrook, K.T. Pattinson, The role of the nitric oxide pathway in brain injury and its treatment from bench to bedside. Exp. Neurol. 263, 235–243 (2015). https://doi.org/10.1016/j.expneurol.2014.10.017

    Article  Google Scholar 

  11. M.I. Remizova, N.I. Kochetygov, K.A. Gerbout, V.L. Lakomkin, A.A. Timoshin, E.N. Burgova, A.F. Vanin, Effect of dinitrosyl iron complexes with glutathione on hemorrhagic shock followed by saline treatment. Eur. J. Pharmacol. 662(1–3), 40–46 (2011). https://doi.org/10.1016/j.ejphar.2011.04.046

    Article  Google Scholar 

  12. M.A. Salykina, E.G. Sorokina, I.A. Krasilnikova, V.P. Reutov, V.G. Pinelis, Effects of selective inhibitors of neuronal and inducible NO-synthase on ATP content and survival of cultured rat cerebellar neurons during hyperstimulation of glutamate receptors. Bull. Exp. Biol. Med 155(1), 40–43 (2013). https://doi.org/10.1007/s10517-013-2075-7

    Article  Google Scholar 

  13. M. Godinez-Rubi, A.E. Rojas-Mayorquin, D. Ortuno-Sahagun, Nitric oxide donors as neuroprotective agents after an ischemic stroke-related inflammatory reaction. Oxid. Med. Cell. Longev. 2013, 1 (2013)

    Article  Google Scholar 

  14. E.B. Manukhina, H.F. Downey, R.T. Mallet, Role of nitric oxide in cardiovascular adaptation to intermittent hypoxia. Exp. Biol. Med. 231, 343–365 (2006)

    Article  Google Scholar 

  15. V.P. Reutov, V.E. Okhotin, A.V. Shuklin, E.G. Sorokina, N.S. Kosicin, V.N. Gurin, Nitric oxide and the cycle in the myocardium: molecular, biochemical and physiological aspects. Uspehi fiziologicheskih nauk 38, 39–58 (2007). (In Russ.)

    Google Scholar 

  16. L. Artinian, L. Zhongm, H. Yangm, V. Rehderm, Nitric oxide as intracellular modulator: internal production of NO increases neuronal excitability via modulation of several ionic conductances. Eur. J. Neurosci. 36, 3333–3343 (2012)

    Article  Google Scholar 

  17. P.M. Balaban, M.V. Roshchin, AKh. Timoshenko, Kh.L. Gainutdinov, TKh. Bogodvid, L.N. Muranova, A.B. Zuzina, T.A. Korshunova, Nitric oxide is necessary for labilization of a consolidated context memory during reconsolidation in terrestrial snails. Eur. J. Neurosci. 40, 2963–2970 (2014). https://doi.org/10.1111/ejn.12642

    Article  Google Scholar 

  18. A.F. Vanin, Dinitrosyl iron complexes with thiol-containing ligands as a “working form” of endogenous nitric oxide. Nitric Oxide 54, 15–29 (2016). https://doi.org/10.1016/j.niox.2016.01.006

    Article  Google Scholar 

  19. A.F. Vanin, A. Huisman, E.E. Van Faassen, Iron dithiocarbamate as spin trap for nitric oxide detection: methods in enzymology. Pitfalls Successes 359, 27–42 (2003). https://doi.org/10.1016/S0076-6879(02)59169-2

    Article  Google Scholar 

  20. J.R. Steinert, T. Chernova, I.D. Forsythe, Nitric oxide signaling in brain function, dysfunction, and dementia. Neuroscientist 16, 435–452 (2010). https://doi.org/10.1177/1073858410366481

    Article  Google Scholar 

  21. K. Maiese, The dynamics of cellular injury: transformation into neuronal and vascular protection. Histol. Histopathol. 16(2), 633–644 (2001). https://doi.org/10.14670/HH-16.633

    Article  Google Scholar 

  22. Z.-N. Guo, A. Shao, L.-S. Tong, W. Sun, J. Liu, Y. Yang, The role of nitric oxide and sympathetic control in cerebral autoregulation in the setting of subarachnoid hemorrhage and traumatic brain injury. Mol. Neurobiol. 53(6), 3606–3615 (2016). https://doi.org/10.1007/s12035-015-9308-x

    Article  Google Scholar 

  23. G.A. Donnan, M. Fisher, M. Macieod, S.M. Davis, Stroke. Lancet 371, 1612–1623 (2008)

    Article  Google Scholar 

  24. Z.Q. Chen, R.T. Mou, D.X. Feng, Z. Wang, G. Chen, The role of nitric oxide in stroke. Med. Gas Res. 7(3), 194–203 (2017). https://doi.org/10.4103/2045-9912.215750

    Article  Google Scholar 

  25. V.P. Reutov, N.V. Samosudova, E.G. Sorokina, A model of glutamate neurotoxicity and mechanisms of the development of the typical pathological process. Biophysics 64(2), 233–250 (2019)

    Article  Google Scholar 

  26. N.A. Terpolilli, M.A. Moskowitz, N. Plesnila, Nitric oxide: considerations for the treatment of ischemic stroke. J. Cereb. Blood Flow Metab. 32, 1332–1346 (2012). https://doi.org/10.1038/jcbfm.2012.12

    Article  Google Scholar 

  27. L. Banci, I. Bertini, S. Ciofi-Baffoni, T. Kozyreva, K. Zovo, P. Palumaa, Affinity gradients drive copper to cellular destinations. Nature 465, 645–648 (2010)

    Article  ADS  Google Scholar 

  28. R.A. Festa, D.J. Thiele, Copper: an essential metal in biology. Curr. Biol. 21(21), R877–R883 (2011)

    Article  Google Scholar 

  29. T. Fukai, M. Ushio-Fukai, Superoxide dismutases: role in redox signaling, vascular function, and diseases. Antioxid. Redox Signal 15(6), 1583–1606 (2011)

    Article  Google Scholar 

  30. N. Hogg, Detection of nitric oxide by electron paramagnetic resonance spectroscopy. Free Radic. Biol. Med. 49, 122–129 (2010)

    Article  Google Scholar 

  31. E.E. van Faassen, M.P. Koeners, J.A. Joles, A.F. Vanin, Detection of basal NO production in rat tissues using iron–dithiocarbamate complexes. Nitric Oxide 18, 279–286 (2008)

    Article  Google Scholar 

  32. Y. Stukach, Stem cells migration to the brain through cranial nerves endings. EuroBiotech J. 1(1), 99–100 (2017)

    Article  Google Scholar 

  33. T. Bogodvid, S. Pashkevich, M. Dosina, A. Zamaro, Y. Tokalchik, G. Yafarova, V. Andrianov, A. Denisov, D. Loiko, K. Gainutdinov, V. Kulchitsky, Effect of intranasal administration of mesenchymal stem cells on the approximate motor activity of rats after simulation of ischemic stroke. Eur. J. Clin. Invest. 49(Suppl 1), 161 (2019). https://doi.org/10.1111/eci.13109

    Article  Google Scholar 

  34. Y. Shanko, A. Zamaro, Y. Takalchik, S. Koulchitsky, S. Pashkevich, E. Panahova, V. Navitskaya, M. Dosina, A. Denisov, S. Bushuk, V. Kulchitsky, Mechanisms of neural network structures recovery in brain trauma. Biomed. J. Sci. Tech. Res. (2018). https://doi.org/10.26717/BJSTR.2018.07.001567

    Article  Google Scholar 

  35. G. Paxinos, C. Watson, The Rat Brain in Stereotaxic Coordinates, 4th edn. (Academic Press, San Diego, 1998)

    Google Scholar 

  36. C. Csonka, T. Pali, P. Bencsik, A. Gorbe, P. Ferdinandy, T. Csont, Measurement of NO in biological samples. Br. J. Pharmacol. 172, 1620–1632 (2015). https://doi.org/10.1111/bph.12832

    Article  Google Scholar 

  37. S.V. Yurtaeva, V.N. Efimov, G.G. Yafarova, A.A. Eremeev, V.S. Iyudin, A.A. Rodionov, Kh.L. Gainutdinov, I.V. Yatsyk, EPR detection of iron storage in rat tissues after simulated microgravity model. Appl. Magn. Res. 47(6), 555–565 (2016)

    Article  Google Scholar 

  38. V.D. Mikoyan, L.N. Kubrina, V.A. Serezhenkov, R.A. Stukan, A.F. Vanin, Complexes of Fe2+ with diethyldithiocarbamate or N-methyl-D-glucamine dithiocarbamate as traps of nitric oxide in animal tissues. Biochim. Biophys. Acta 1336, 225–234 (1997). https://doi.org/10.1016/S0304-4165(97)00032-9

    Article  Google Scholar 

  39. A.I. Ismailova, O.I. Gnezdilov, L.N. Muranova, A.A. Obynochny, V.V. Andrianov, Kh.L. Gainutdinov, A.G. Nasyrova, R.R. Nigmatullina, F.F. Rahmatullina, A.L. Zefirov, ESR study of the nitric oxide production in tissues of animals under the external influence on the functioning of the cardiovascular and nervous systems. Appl. Magn. Reson 28, 421–430 (2005)

    Article  Google Scholar 

  40. V.V. Andrianov, S.G. Pashkevich, G.G. Yafarova, A.A. Denisov, V.S. Iyudin, TKh. Bogodvid, M.O. Dosina, V.A. Kulchitsky, Kh.L. Gainutdinov, Changes of nitric oxide content in the rat hippocampus, heart and liver in acute phase of ischemia. Appl. Magn. Reson. 47(9), 965–976 (2016)

    Article  Google Scholar 

  41. Kh.L. Gainutdinov, V.V. Andrianov, V.S. Iyudin, S.V. Yurtaeva, G.G. Jafarova, R.I. Faisullina, F.G. Sitdikov, EPR study of nitric oxide production in rat tissues under hypokinesia. Biophysics 58, 203–205 (2013)

    Article  Google Scholar 

  42. M.A. Jakubowska, J. Pyka, D. Michalczyk-Wetula, K. Baczyński, M. Cieśla, A. Susz, P.E. Ferdek, B.K. Płonka, L. Fiedor, P.M. Płonka, Electron paramagnetic resonance spectroscopy reveals alterations in the redox state of endogenous copper and iron complexes in photodynamic stress-induced ischemic mouse liver. Redox Biol. 34, 566 (2020)

    Article  Google Scholar 

  43. Y. Suzuki, S. Fujii, T. Tominaga, T. Yoshimoto, T. Yoshimura, H. Kamada, The origin of an EPR signal observed in dithiocarbamate-loaded tissues Copper(II)-dithiocarbamate complexes account for the narrow hyperfine lines. Biochim. Biophys. Acta 1335(3), 242–245 (1997). https://doi.org/10.1016/s0304-4165(97)00027-5

    Article  Google Scholar 

  44. Y. Shanko, V. Navitskaya, A. Zamaro, S. Krivenko, S. Koulchitsky, V. Kulchitsky, Application of stem cells perineural migration in patients with stroke. J. Neurol. Stroke 9(2), 111–112 (2019). https://doi.org/10.15406/jnsk.2019.09.00358

    Article  Google Scholar 

  45. Y. Shanko, V.V. Navitskaya, A. Zamaro, S. Krivenko, M. Zafranskaya, S. Pashkevich, S. Koulchitsky, Y.S. Takalchik, A. Denisov, V. Kulchitsky, Prospects of perineural administration of autologous mesenchymal stem cells of adipose tissue in patients with cerebral infarction. Biomed J. Sci. Tech. Res. 10(1), 1–3 (2018). https://doi.org/10.26717/BJSTR.2018.10.001884

    Article  Google Scholar 

  46. M.L. Hoff, A. Fabrizius, N.U. Czech-Damal, L.P. Folkow, T. Burmester, Transcriptome analysis identifies key metabolic changes in the hooded seal (Cystophora cristata) brain in response to hypoxia and reoxygenation. PLoS ONE 12(1), e0169366 (2017). https://doi.org/10.1371/journal.pone.0169366

    Article  Google Scholar 

  47. E.B. Manukhina, I.Y. Malyshev, B.V. Smirin, S.Y. Mashina, V.A. Saltykova, A.F. Vanin, Production and storage of nitric oxide in adaptation to hypoxia. Nitric Oxide 3, 393–401 (1999). https://doi.org/10.1006/niox.1999.0244

    Article  Google Scholar 

  48. K.P. Doyle, R.P. Simon, M.P. Stenzel-Poore, Mechanisms of ischemic brain damage. Neurophrmacology 55, 310–318 (2008)

    Article  Google Scholar 

  49. L.X. Liu, Y.J. Yang, Y.J. Jia, A model of hypoxic-ischemic brain damage in the neonatal rats. Bull. Hunan Med. Univ. 28(2), 133–136 (2003)

    Google Scholar 

  50. M. Ziaja, J. Pyka, A. Machowska, A. Maslanka, P.M. Plonka, Nitric oxide spin-trapping and NADPH-diaphorase activity in mature rat brain after injury. J. Neurotrauma. 24(12), 1845–1854 (2007)

    Article  Google Scholar 

  51. G. Inesi, Molecular features of copper binding proteins involved in copper homeostasis. IUBMB Life 69(4), 211–217 (2017)

    Article  Google Scholar 

  52. A.G. Dalecki, M. Haeili, S. Shah, A. Speer, M. Niederweis, O. Kutsch, F. Wolschendorf, Disulfiram and copper ions kill Mycobacterium tuberculosis in a synergistic manner. Antimicrob. Agents Chemother. 59(8), 4835–4844 (2015). https://doi.org/10.1128/AAC.00692-15

    Article  Google Scholar 

  53. V.V. Andrianov, G.G. Yafarova, S.G. Pashkevich, Y.P. Tokalchik, M.O. Dosina, A.S. Zamaro, TKh. Bogodvid, V.S. Iyudin, L.V. Bazan, A.A. Denisov, V.A. Kulchitsky, Kh.L. Gainutdinov, Changes of the nitric oxide and copper content in the olfactory bulbs of rats brain after modeling of brain stroke and intranasal administration of mesenchymal stem cells. Appl. Magn. Res. 51(4), 375–387 (2020)

    Article  Google Scholar 

  54. O.G. Deryagin, S.A. Gavrilova, Kh.L. Gainutdinov, A.V. Golubeva, V.V. Andrianov, G.G. Yafarova, S.V. Buravkov, V.B. Koshelev, Molecular bases of brain preconditioning. Front. Neurosci. 11, 427 (2017). https://doi.org/10.3389/fnins.2017.00427

    Article  Google Scholar 

  55. M.H.K. Ansari, P. Karimi, N. Shakib, S.M. Beyrami, The neuroprotective effect of sodium nitrite on ischemic stroke-induced mitochondrial dysfunction via down regulation of intrinsic apoptosis pathway. Crescent J. Medic. Biol. Sci. 5(1), 50–56 (2018)

    Google Scholar 

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Acknowledgements

The authors thank Abdulla Chihab and Dinara Silantyeva for help in preparation of this publication.

Funding

Ischemia modeling was carried out at the Brain Center, Institute of Physiology of the National Academy of Sciences of Belarus (Minsk, Belarus) and supported by the Belarusian Republican Foundation for Fundamental Research (Project # B18P-227). Measurement of EPR spectra of samples was carried out in Zavoisky Physical-Technical Institute, KazSC RAS within the framework of a state assignment Federal Research Center of KazSC RAS. The storage of samples and processing of results was carried out at Kazan Federal University (Kazan, Russia) in the framework of fulfilling the state assignment No. 0671-2020-0059.

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Andrianov, V.V., Kulchitsky, V.A., Yafarova, G.G. et al. Comparative Study of the Intensity of Nitric Oxide Production and Copper Content in Hippocampus of Rats After Modeling of Hemorrhagic Stroke and Brain Injury. Appl Magn Reson 52, 1657–1669 (2021). https://doi.org/10.1007/s00723-021-01423-1

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