Psychopharmacological Effects of JNK Inhibitor in Posthypoxic Encephalopathy and Mechanisms of Their Development

Abstract

Psychopharmacological effects of JNK inhibitor were studied using a mouse model of posthypoxic encephalopathy. The preparation exhibited a pronounced cerebroprotective effect manifested in normalization of orientation and exploratory behavior and conditioned responses in posthypoxic mice. These effects were accompanied by marked elevation of neural stem cell content in the paraventricular region of the brain.

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

“…The animals were removed from the experiment (sacrificed) using CO2 cameras, except for the groups of rats used for histological examination (these animals were killed by decapitation). The cerebral ischemia [16] was induced in rats under ether anesthesia by complete ligation of the left carotid artery and restriction of blood flow in the right carotid artery by 50% by means of partial ligation of artery under the control of electromagnetic flow meter MFV-1100 (Nihon Kohden, Japan). Sham-operated animals were experienced similar surgery but without coronary artery ligation and were used as control animals.…”

“…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].…”

“…Alkaloids, which possess a stimulating effect on the functions of progenitor cells of various classes, were identified [16,18,19]. Mechanisms of action of these substances are both a direct effect on the receptor apparatus of progenitor cells, and their influence on the elements of the microenvironment of tissues.…”

Neuroprotective properties of the C-Jun N-terminal kinase (JNK) inhibitor in hypoxic hypoxia

“…Выявленная динамика двигательной активности соответствовала полученным нами ранее результатам о формировании нарушений ориентировочно-исследовательского поведения животных при постгипоксической ýнцефалопатии, связанной с расстройствами когнитивной, а не локомоторной функции ЦНС [10,11]. Подтверждением ýтого являлось резкое снижение уровня воспроизведения УРПИ у мышей, подвергшихся гипоксии (табл.…”

“…Гольдберга, Томский НИМЦ РАН, проведен цикл работ по выявлению роли JNK (c-Jun N-terminal kinases, c-Jun N-концевая киназа) в жизнедеятельности родоначальных клеток различных классов. На модели постгипоксической ýнцефалопатии обнаружено терапевтическое действие ингибитора данной сигнальной молекулы (при его введении после моделирования патологического состояния), связанное с активацией резидентных нейральных стволовых клеток (СК) субвентрикулярной зоны головного мозга ýкспериментальных животных [10]. В то же время представляется актуальным изучение возможности профилактического использования указанного модификатора активности JNK для предупреждения развития патологии мозга после кислородной недостаточности.…”