Neuroprotective effects of thromboxane receptor antagonist SQ 29,548 after pilocarpine-induced status epilepticus in mice.

Autor: Mello FK; Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil., Freitas ML; Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil., Souto NS; Graduate Program in Food Science and Technology, Federal University of Santa Maria, Santa Maria, Brazil., Zorzi VN; Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria, Santa Maria, Brazil., Moreira MP; Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil., Neuberger B; Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil., Costa KG; Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil., Fighera MR; Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil; Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria, Santa Maria, Brazil., Royes LF; Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil; Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria, Santa Maria, Brazil., Furian AF; Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil; Graduate Program in Food Science and Technology, Federal University of Santa Maria, Santa Maria, Brazil., Oliveira MS; Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil. Electronic address: ms.oliveira@ufsm.br.
Jazyk: angličtina
Zdroj: Epilepsy research [Epilepsy Res] 2020 Feb; Vol. 160, pp. 106277. Date of Electronic Publication: 2020 Jan 16.
DOI: 10.1016/j.eplepsyres.2020.106277
Abstrakt: Thromboxane A 2 (TXA 2 ) is an important eicosanoid in the cardiovascular system, and increasing evidence suggests that TXA 2 receptors (TPs) and their ligands may constitute valuable tools for the development of neuroprotective drugs. However, the role of TPs on seizure-induced damage has not been investigated. Therefore, we evaluated the effects of SQ 29,548, a potent and selective TP antagonist-on neuromotor performance, neurodegeneration, reactive astrocytosis, and c-Fos protein immunoreactivity after pilocarpine-induced status epilepticus (SE) in mice. Adult C57BL/6 mice received intracerebroventricular SQ 29,548 injections 90 min and 24 h after pilocarpine-induced SE. We found that SQ 29,548 prevented the impairment of neuromotor performance (Neuroscore test) 48 h after pilocarpine-induced SE. Data analysis suggested the existence of two subgroups of SQ 29,548-treated post-SE animals. Eight out of 12 SQ 29,548-treated animals displayed Neuroscore values identical to those of vehicle-treated controls, and were considered SQ 29,548 responders. However, 4 out of 12 SQ 29,548-treated animals did not show any improvement in Neuroscore values, and were considered SQ 29,548 non-responders. Treatment with SQ 29,548 attenuated SE-induced increase in the number of FJC- or GFAP-positive cells in the hippocampus of SQ 29,548 responders. In addition, SQ 29,548 prevented the SE-elicited increase of c-Fos immunoreactivity in the hippocampus. In summary, our results suggest that the TP antagonist (SQ 29,548) improves neurological outcome after pilocarpine-induced SE in mice. The existence of SQ 29,548 responders and non-responders was suggested by results from the Neuroscore test. Additional studies are needed to understand the mechanisms underlying these findings, as well as the potential uses of TP antagonists in the treatment of seizure-induced damage.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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