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

*Corresponding author for this work

Research output: Chapter in Book or Report/Conference proceedingChapterpeer-review

7 Citations (Scopus)

Abstract

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

Original languageEnglish
Title of host publicationSystems Biology of Free Radicals and Antioxidants
PublisherSpringer-Verlag Berlin Heidelberg
Pages2023-2032
Number of pages10
ISBN (Electronic)9783642300189
ISBN (Print)3642300170, 9783642300172
DOIs
Publication statusPublished - 1 May 2012
Externally publishedYes

Keywords

  • <sup>31</sup>P NMR NMR
  • Brain 3-VO hypoperfusion
  • Creatine kinase
  • Mitochondria
  • Oxidative phosphorylation

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