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

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Systems Biology of Free Radicals and Antioxidants

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 disorder s due to chronic 3-VO, thus, may participate in vascular cognitive impairment and neuronal degeneration.

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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 permission Journal 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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Correspondence to Gjumrakch Aliev .

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Aliev, G. et al. (2009). The Three-Vessel Occlusion as a Model of Vascular Dementia – Oxidative Stress and Mitochondrial Failure as an Indicator of Brain Hypoperfusion. In: Laher, I. (eds) Systems Biology of Free Radicals and Antioxidants. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30018-9_205

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