No abstract

Anxiolytic agent afobazole (10 mg/kg intraperitoneally) 24 h after ischemia restores impaired balance of excitatory and inhibitory amino acids in the striatum of mongrel rats, normalizes their content to control levels, and activates endogenous taurine-dependent system of neuroprotection.

ÒÐÎÏÎÊÑÈÍ -ÍÎÂÎÅ ÑÐÅÄÑÒÂÎ ÄËß ËÅ×ÅÍÈß ÌÈÃÐÅÍÈÔÃÁÍÓ "ÍÈÈ ôàðìàêîëîãèè èì. Â. Â. Çàêóñîâà", Ðîññèÿ, 125315, Ìîñêâà, Áàëòèéñêàÿ óë., 8 Ðàçðàáîòàíî íîâîå ïðîòèâîìèãðåíåâîå ñðåäñòâî -òðîïîêñèí (3-(3,4,5-òðèìåòîêñèáåí-çîèëîêñèèìèíî)-8-ìåòèë-8-àçàáèöèêëî[3,2,1]îêòàíà ãèäðîõëîðèä), êîòîðîå ïðåäóïðåae-äàåò èëè çíà÷èòåëüíî îñëàáëÿåò êîíñòðèêòîðíûå ðåàêöèè ìîçãîâûõ ñîñóäîâ, âûçâàííûå ñåðîòîíèíîì (5ÍÒ) èëè àãîíèñòîì 5HT 2B/2C -ðåöåïòîðîâ -ìåòà-õëîðôåíèëïèïåðàçèíîì (m-CPP) ó aeèâîòíûõ èíòàêòíûõ è â óñëîâèÿõ èøåìè÷åñêîãî ïîðàaeåíèÿ ìîçãà. Ïðåïàðàò ïðîÿâëÿåò àôôèííîñòü ê 5ÍÒ 2 òèïà ðåöåïòîðàì ìîçãà è îêàçûâàåò àíòèàãðåãàöèîííîå äåéñòâèå. Îí íå îáëàäàåò âûðàaeåííûìè íåéðîòðîïíûìè ñâîéñòâàìè è íå èçìåíÿåò ðåàê-öèè àðòåðèàëüíîãî äàâëåíèÿ íà íîðàäðåíàëèí, àöåòèëõîëèí è ãèñòàìèí. Ïèëîòíîå êëè-íè÷åñêîå èññëåäîâàíèå òðîïîêñèíà ñâèäåòåëüñòâóåò î åãî âûñîêîé ýôôåêòèâíîñòè ïðè ìåaeïðèñòóïíîì ëå÷åíèè ÷àñòûõ è òÿaeåëûõ ïðèñòóïîâ ìèãðåíè. Êëþ÷åâûå

Изучение влияния пикамилона (50 мг/кг внутривенно) на мозговое кровообращение крыс в условиях сочетанной сосудистой патологии мозга и сердца позволило установить, что в этих условиях препарат вызывает существенное увеличение мозгового кровотока (на 38 %). Менее выраженное увеличение кровотока (на 13 %) наблюдается после экспериментального инфаркта миокарда. Анализ механизма цереброваскулярного эффекта пикамилона в условиях глобальной преходящей ишемии головного мозга показал, что хлорные каналы ГАМКА-рецепторов участвуют в реализации сосудорасширяющего эффекта препарата. Вместе с тем, нимодипин при сочетанной сосудистой патологии мозга и сердца не только не увеличивает, но даже ухудшает церебральную гемодинамику. Следовательно, в условиях наиболее тяжелой сосудистой патологии, а именно сочетанной, ГАМКА-рецепторная система сосудов мозга играет более значимую роль в регуляции мозгового кровообращения по сравнению с медленными кальциевыми каналами.

Introduction: The aim of the study was to compare the neuroprotective and cerebrovascular effects of bioactive, endogenous lipid – N-arachidonoyl-GABA (AA-GABA) and GABA conjugate with prostaglandin E2 (PGE2-GABA) by evaluation of a morphological state of rat brain tissue and lipofuscin levels under the condition of permanent focal brain ischemia, as well as cerebral circulation under the condition of global transient ischemia. Materials and methods: The study has been implemented using the models of the left middle cerebral artery occlusion (MCAO) and global transient ischemia of the brain. A morphological examination of the brain tissue, a registration of local blood flow by laser flowmeter, and quantitative measurement of lipofuscin by fluorescence spectroscopy were used. Results and discussion: AA-GABA and the putative COX-2 metabolite PGE2-GABA showed significant neuroprotective and cerebrovascular effects in rat models of global and focal cerebral ischemia. In the MCAO model, AA-GABA and PGE2-GABA at a dose of 2 mg/kg/day administered i.p. for 6 or 12 days led to: 1) significant restoration of neurons and glial cells with intracellular regeneration of cytoplasmic and nuclear structures, 2) decrease in brain tissue edema; 3) attenuated thrombosis and stasis, and 4) absence of large necrotic foci in rat brain tissue. AA-GABA and PGE2-GABA at the same dose prevented excessive accumulation of lipofuscin in both brain hemispheres in rats with MCAO. All the studied compounds increase cerebral blood circulation in rats subjected to global transient ischemia. However, the cerebrovascular effect of PGE2-GABA was superior to the activity of AA-GABA and all other tested compounds. AA-GABA and PGE2-GABA, unlike PGE2 and nimodipine, increase the cerebral blood flow in rats with global transient brain ischemia and have no influence on the intact animals. Apparently, the GABAergic vascular system of the brain is involved in the mechanisms of the neuroprotective action of AA-GABA and PGE2-GABA. Conclusion: For the first time, we demonstrated the ability of AA-GABA and its putative metabolite COX-2 PGE2-GABA to improve cerebral circulation, attenuate structural damage and lipofuscin accumulation during cerebral ischemia. The natural origin of AA-GABA, which possesses neuroprotective and cerebrovascular activity, as well as anti-aggregatory activity, allows considering AA-GABA as one of the endogenous protective factors in ischemic brain lesions. Graphical abstract: