Psychopharmacological Effects of Alkaloid Z77 under Conditions of Posthypoxic Encephalopathy and Mechanisms of Their Development

Abstract

Psychopharmacological effects of atisine-type diterpene alkaloid Z77 were studied under conditions of experimental posthypoxic encephalopathy. The preparation had a pronounced cerebroprotective effect consisting in normalization of orientation and exploratory behavior and conditioned activity in experimental animals. These changes were accompanied by significant increase in the number of neural stem cells in the paraventricular region of the brain and markedly enhanced production of neurotrophic growth factors by neural tissue microenvironment cells.

Halogenated (Cl-ion) songorine is a new original agonist of fibroblast growth factor receptors of neuronal-committed progenitors possessing neuroregenerative effect after cerebral ischemia and hypoxia in experimental animals

“…These changes were developed on the background of spontaneous mortality of animals which underwent hypoxia, reaching 22.4% on the 21st day of the experiment. The revealed behavioral disorders conformed fully to posthypoxic changes in CNS activity that were characteristic for this model, and reflected a marked degree of brain damage [1,6,15]. The administration of mSON after hypoxic exposure was accompanied by practically complete normalization of all studied parameters.…”

“…They also do not possess the necessary pharmacokinetic characteristics. Virtually they unable to penetrate through the blood-brain barrier, and their protein nature predetermines high immunogenicity and the only possible parenteral way of administration [7, [15][16][17][34][35][36][37]. Although the most appropriate in regenerative medicine is the oral use of medicines since they are expected to be used by long-lasting, repeatedly recurrent courses [1].…”

“…After incubation, the number of CFU-N (see above) was counted. While determination of the secretory function of neural tissue cells the effect of conditioned media of a 2-day culture of cells from the SVZ obtained in a similar way on the level of formation of CFU-N from PSA-NCAM + cells in the test systemcolony-stimulating activity (CSA) of supernatants was studied [15].…”

“…In all cases, there was a substantial increase in the coefficient of motion asymmetry, which is considered to be a reflection of "depletion" of the motor activity in experimental animals ( Table 3). The fact of a differently directed shift of horizontal activity in the first and second periods indirectly indicates a disorder of rather a cognitive function than research one of the central nervous system [15]. In addition, the modeling of encephalopathy was accompanied by the decrease in the level of reproduction of conditioned reflex of passive avoidance to 31% on the 14th and 21st days, while the values of this parameter in intact mice on the 14th and 21st days were 100% and 85%, respectively (Table 4).…”

“…In this case more physiological and perspective approach to solving the problems of regenerative medicine, including treatment of central nervous system diseases, is considered to be pharmacological stimulation of endogenous SC functions by imitation of the activity of natural regulatory systems [7]. During development of "Pharmacological strategy of regenerative medicine" at the Goldberg Research Institute of Pharmacology and Regenerative Medicine the principal possibility and high effectiveness of this approach to the therapy of a number of diseases, including pathological conditions of the central nervous system, were demonstrated in the experiment [1, 6, 7, [14][15][16][17][18][19].…”