Pharmacologicalmodification of thegabaergicsystem as a potentialvariant of cerebral protection in acute cerebral ischemia
DOI:
https://doi.org/10.15587/2313-8416.2015.51994Keywords:
derivatives of gamma-aminobutyric acid, acute cerebral ischemia, cerebral protectionAbstract
The aim is to study the possible impact of some derivatives of gamma-aminobutyric acid (GABA), piracetam, picamilon and Krebs cycle intermediates - succinate (as sodium salt) on the pathobiochemical changes in the central nervous system, that occur under experimental playing of acute ischemic tissue damage of the cerebrum.
Research methods: The study was conducted in 96 rats Wistar, who were on a standardized vivarium diet. Cerebral ischemia was caused by bond of the unilateral common carotid artery. All drugs were administered intraperitoneally once daily for 4 days after modeling of an acute cerebral ischemia after which animals were withdrawn from experiment. In the brain tissues concentrations of pyruvic, izocitric, dairy and apple acids were determined. The activity of antioxidant enzymes: catalase and superoxide dysmutaza. In addition, the brain tissues the contents of lipid peroxidation products were evaluated – diene conjugates and malonic dialdehyde. Level of brain energy production was judged by the content of the adenylic nucleotide and also phosphocreatine . The degree of destruction of the brain cells was assessed by activity of the enzyme lactate dehydrogenase in the blood and brain fraction of the creatine phosphokinase.
Research results: As a result of studies, on the 4th day of ischemia a significant carbohydrate metabolism is detected, which is reflected in the sharp strengthening of anaerobic glycolysis and reduced activity of the Krebs cycle reactions, as evidenced by a significant increase in quantity of lactate and decrease in quantity of malate, isocitrate and pyruvate.
A sharp strengthening of anaerobic glycolysis results in the accumulation of oxidized products and intermediates especially the latter product – lactic acid. Metabolic acidosis develops against the background of energy failure, which leads to activation of lipid peroxidation reactions. Courses appointment of the cyclic derivatives of GABA piracetam, especially Picamilon, resulted in significantly greater improvement in metabolic parameters compared with sodium succinate may to some extent explained by the higher bioavailability of these agents cells. The impact of these drugs on the nodal points of disturbed metabolism was almost equal and different in antioxidant activity. As to normalization of lipid peroxidation reactions Picamilon was most active.
Conclusions: Thus, as a result of the research the following conclusions may be done.
1. Bilateral bond of the common carotid artery, accompanied by severe biochemical changes in the brain tissues, that is largely similar to clinical manifestations of acute ischemic stroke.
2. Course appointment of GABA derivatives in the acute period of ischemic lesions of the tissues in varyious degrees improves metabolic status of the ischemic brain and detect different degrees of manifestation of cerebral protective action.
3. The activity of various GABA derivatives in respect to the different links of pathogenesis of ischemic stroke is not the same, that leads to insufficient sustainable improvement of impaired metabolism when used alone, in the long run may be justification for finding effective combinations of cerebral protective means with different mechanism of action.
4. Among the studied drugs, the most active and balanced action was presented by Picamilon drug
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