Positive Pharmacological Modulation of Hsp70 in Recovery of Brain Energy Metabolism in Various Models of Cerebral Ischemia

Abstract

The aim of this research was to analyze the neuroprotective action of drugs via an evidence-based approach to analyzing the expression of endogenous neuroprotection factors in various experimental models of cerebral ischemia in Wistar white rats (intracerebral hemorrhage, carotid artery occlusion, prenatal hypoxia) to further substantiate their use in the treatment of CNS damage. The experimental studies were carried out in accordance with the “Regulations on the Use of Animals in Biomedical Research” and the European Convention on the Protection of Animals Used for Scientific and Other Purposes. The experiment was approved by the Bioethics Committee of Zaporizhzhia State Medical University. In studies, it was found that pharmacotherapy of emerging mitochondrial disorders with modulators of HSP70 expression—Cerebrocurin (composition: neuropeptides, S-100 proteins, reelin, factor nerve growth (NGF)), Glutoredoxin, Tamoxifen, (S)-2,6-diaminohexanoic acid, 3-methyl-1,2,4-triazolyl-5-thioacetate significantly (p p p < 0.05) decrease in ultrastructural disorders of mitochondria. The energy-tropic and mitoprotective effects of the studied drugs are associated with their ability to protect mitochondrial proteins from oxidative damage by increasing the concentration of HSP70, prolong the lifespan of HSF-1a, and activate alternative energy generation pathways.

Keywords

• CNS
• ischemia
• endogenous neuroprotection
• HSP70