Recurrent Hypoglicemia Affects S100B Plasma Concentration And S100b Hippocampal Expression In Rats

E. Mazukina(1), junior researcher, E. Shekunova(1), PhD, senior researcher, V. Kashkin(1, 2), PhD, senior researcher, N. Faustova(1), PhD, senior researcher, M. Makarova(1), Dr. Med. Sci., deputy director, V. Makarov(1), Dr. Med. Sci., professor, director 1-Research-and-manufacturing company «Houm of Pharmacy» Russia, 188663, Leningradskiy region, Vsevolozhskiy district, Kuzmolovskiy, st. Zavodskaya, 3. b. 245; 2-Valdman Institute of Pharmacology, Pavlov First St. Petersburg State Medical University, 6–8, Lev Tolstoy str., Saint Petersburg, 197022, Russia E-mail: mazukina.ev@doclinika.ru

Abstract

A significant decrease in blood glucose levels leads to the development of delayed cognitive impairment, caused by hypoglycemia damage of brain neurons. It has been shown that both moderate and severe recurrent hypoglycemia resulted in neuronal damage in several areas of the brain, including the neocortex and hippocampus in rats. In this experiment moderate hypoglycemia was induced by daily insulin aspart subcutaneous administration (15 U/kg, for 5 days), 60 minutes later blood glucose level was increased by intraperitoneal injection of glucose solution. Cognitive deficits were assessed in the Morris Water Maze test on the 35th day after the pathology induction. Considering the greatest susceptibility of the hippocampal neurons to the negative effect of hypoglycemia, to assess the degree of expression of the S100b protein in the CA1 region of the hippocampus was carried out using immunohistochemical analysis. In addition, the S100b level changes in serum was estimated The episodes of moderate insulin induced hypoglycemia (blood glucose level – 2,1 mmol/l) lasted up to 60 minutes. Cognitive functions estimation revealed that the animals with pathology did not “patrol” the quadrant where the platform was previously (during training) located. These animals spent less time in the target quadrant compared to control animals (t-test, p<0,05). Evaluation of the blood plasma S100b concentration showed that immediately after the pathology induction and up to the 35th day of the experiment in animals undergoing episodes of hypoglycemia, the protein level was significantly increased compared with the control group. An increase in blood protein concentration correlated with an increase in expression of S100b protein in the CA1 zone of the hippocampus by the 35th day of the experiment. The results suggest that the change in S100b concentration is an important diagnostic biochemical marker of brain damage, which can be assessed repeatedly during experiment and can be used for estimation of new medicines efficiency.

References

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