The Three-Vessel Occlusion as a Model of Vascular Dementia – Oxidative Stress and Mitochondrial Failure as an Indicator of Brain Hypoperfusion

  • Gjumrakch Aliev
  • Jaromir Horecký
  • Olga Vančová
  • Ghulam Md Ashraf
  • Iftekhar Hassan
  • Valentin Bragin
  • Ilya Bragin
  • Elena Shevtsova
  • Sergey G. Klochkov
  • Elena A. Kosenko
  • Ramon Cacabelos
  • Sergey O. Bachurin
  • Valery V. Benberin
  • Yury G. Kaminsky
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Abstract

Brain energy disorders and oxidative stress due to chronic hypoperfusion are considered to be major risk factors in the pathogenesis of dementia. The aim of our study was to evaluate changes of brain creatine kinase (BB-CK) reaction and mitochondrial respiratory chain function in male Wistar rats exposed to chronic cerebral hypoperfusion. Three-vessel occlusion (3-VO) was accomplished without thoracotomy using a minimally invasive surgical approach for the occlusion of the brachiocephalic trunk and the left common carotid artery (CCA). The forward rate constant of creatine kinase (kfor) was measured in vivo by saturation transfer of 31P magnetic resonance spectroscopy (MRS) at 2 and 10 weeks of permanent 3-VO. The function of the mitochondrial respiratory chain in vitro was assessed polarographically at 10 weeks after 3-VO. As compared to the controls, the significant 42 % reduction of kfor at 2 respiration. 10 weeks indicated disorders in brain energy metabolism, which is in agreement with the 12 % decrease of the oxidative phosphorylation coefficient (ADP:O) and with the 14 % decrease of the oxidative phosphorylation rate (OPR) measured in isolated mitochondria obtained from the hippocampal tissue. Oxidative modification of the creatine kinase system (inactivation of enzymes) and metabolic disorders due to chronic 3-VO, thus, may participate in vascular cognitive impairment and neuronal degeneration.

Keywords

31P NMR Brain 3-VO hypoperfusion Creatine kinase Mitochondria Oxidative phosphorylation 

Notes

Acknowledgments

This project is supported by Slovak Research and Development Agency (project APVV-21-022004) and GALLY International Biomedical Research Consulting LLC., San Antonio, Texas, USA. We are very grateful to Ms. Galina Alieva for her editorial works.

Conflict of Interest

Authors declared no conflict of interest.

Disclosure

Part of information included in this chapter has been previously published (Horecký, J., Baciak, L., Kašparová, S., Pacheco, G., Aliev, G. and Vancová, O. Minimally invasive surgical approach for three-vessel occlusion as a model of vascular dementia in the rat-brain bioenergetics assay. J Neurol Sci. 2009; 283(1–2):178–181. doi: 10.1016/j.jns.2009.02.348. Epub 2009 Mar 9). Reprinted with permissionJournal of the Neurological Sciences: Horecký, J., Baciak, L., Kašparová, S., Pacheco, G., Aliev, G. and Vancová, O. Minimally invasive surgical approach for three-vessel occlusion as a model of vascular dementia in the rat-brain. This article represents an update of current knowledge regarding the implication of oxidative stress and mitochondrial failure as an indicator of brain hypoperfusion in the context of the three-vessel occlusion as a model for the vascular dementia.

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Copyright information

© Elsevier 2009

Authors and Affiliations

  • Gjumrakch Aliev
    • 1
    • 2
  • Jaromir Horecký
    • 3
  • Olga Vančová
    • 4
  • Ghulam Md Ashraf
    • 5
  • Iftekhar Hassan
    • 6
  • Valentin Bragin
    • 7
  • Ilya Bragin
    • 8
  • Elena Shevtsova
    • 9
  • Sergey G. Klochkov
    • 9
  • Elena A. Kosenko
    • 10
  • Ramon Cacabelos
    • 12
  • Sergey O. Bachurin
    • 9
  • Valery V. Benberin
    • 11
  • Yury G. Kaminsky
    • 10
  1. 1.GALLY International Biomedical Research Consulting LLCSan AntonioUSA
  2. 2.School of Health Science and Healthcare AdministrationUniversity of AtlantaAtlantaUSA
  3. 3.Surgical Pathophysiology and Tissue Engineering CenterSlovak Medical UniversityBratislavaSlovak Republic
  4. 4.Pharmacobiochemical LaboratoryComenius University School of MedicineBratislavaSlovak Republic
  5. 5.King Fahd Medical Research CenterKing Abdulaziz UniversityJeddahKingdom of Saudi Arabia
  6. 6.Department of Biochemistry, Faculty of Life SciencesAligarh Muslim UniversityAligarhIndia
  7. 7.Stress Relief and Memory Training CenterBrooklynUSA
  8. 8.Upstate Medical UniversitySyracuseUSA
  9. 9.Institute of Physiologically Active CompoundsRussian Academy of SciencesChernogolovka, Moscow RegionRussian Federation
  10. 10.Institute of Theoretical and Experimental BiophysicsRussian Academy of SciencesPushchino Moscow RegionRussian Federation
  11. 11.Medical Center of the Administration of the President of the Republic of KazakhstanAstanaKazakhstan
  12. 12.EuroEspes Biomedical Research Center, Institute for CNS Disorders and Genomic MedicineCamilo José Cela UniversityBergondo La CoruñaSpain

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