Effects of a compound from the group of substituted thiadiazines with hypothermia inducing properties on brain metabolism in rats, a study in vivo and in vitro / Shevelev O. B.,Illarionova N. B.,Petrovski D. V.,Sarapultsev A. P.,Chupakhin O. N.,Moshkin M. P. // PLOS ONE. - 2017. - V. 12, l. 7.

ISSN/EISSN:

1932-6203 / нет данных

Type:

Article

Abstract:

The aim of the present study was to examine how administration of a compound of 1,3,4-thiadiazine class 2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobromide (L-17) with hypothermia inducing properties affects the brain metabolism. The mechanism by which L-17 induces hypothermia is unknown; it may involve hypothalamic central thermoregulation as well as act via inhibition of energy metabolism. We tested the hypothesis that L-17 may induce hypothermia by directly inhibiting energy metabolism. The study in vivo was carried out on Sprague-Dawley adult rats. Two doses of L-17 were administered (190 mg/kg and 760 mg/kg). Brain metabolites were analyzed in control and treated groups using magnetic resonance spectroscopy, along with blood flow rate measurements in carotid arteries and body temperature measurements. Further in vitro studies on primary cultures from rat hippocampus were carried out to perform a mitochondria function test of L-17 preincubation (100 mu M, 30 min). Analysis of brain metabolites showed no significant changes in 190 mg/kg treated group along with a significant reduction in body temperature by 1.5 degrees C. However, administration of L-17 in higher dose 760 mg/kg provoked changes in brain metabolites indicative of neurotoxicity as well as reduction in carotid arteries flow rate. In addition, a balance change of excitatory and inhibitory neurotransmitters was observed. The L-17 pre-incubation with cell primary cultures from rat brain showed no significant changes in mitochondrial function. The results obtained in the study indicate that acute administration of L-17 190 mg/kg in rats induces mild hypothermia with no adverse effects onto brain metabolism.

Author keywords:

MAGNETIC-RESONANCE; 1,3,4-THIADIAZINE DERIVATIVES; MODERATE HYPOTHERMIA; SPECTROSCOPY; MECHANISMS; PROTECTION; RECEPTORS; MARKER; INJURY

DOI:

10.1371/journal.pone.0180739

Web of Science ID:

ISI:000405272200089

Соавторы в МНС:

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Другие поля

Поле	Значение
Month	JUL 5
Publisher	PUBLIC LIBRARY SCIENCE
Address	1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
Language	English
Article-Number	e0180739
Keywords-Plus	MAGNETIC-RESONANCE; 1,3,4-THIADIAZINE DERIVATIVES; MODERATE HYPOTHERMIA; SPECTROSCOPY; MECHANISMS; PROTECTION; RECEPTORS; MARKER; INJURY
Research-Areas	Science \& Technology - Other Topics
Web-of-Science-Categories	Multidisciplinary Sciences
Author-Email	shevelev.oleg.nsk@gmail.com
ResearcherID-Numbers	Moshkin, Mikhail/N-7620-2014 Sarapultsev, Alexey/K-7220-2012
ORCID-Numbers	Sarapultsev, Alexey/0000-0003-3101-9655 Shevelev, Oleg/0000-0003-3200-958X
Funding-Acknowledgement	Russian Science Foundation {[}14-14-00221]
Funding-Text	The study was supported by the Russian Science Foundation (grant No 14-14-00221) http://www.rscf.ru/. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Number-of-Cited-References	35
Usage-Count-Last-180-days	1
Usage-Count-Since-2013	1
Journal-ISO	PLoS One
Doc-Delivery-Number	FA2LF