Sepsis impairs the propagation of cortical spreading depression in rats and this effect is prevented by antioxidant extract

ABSTRACT

Sepsis is a clinical syndrome with high morbidity and mortality. It is characterized by acute inflammatory response and oxidative stress, which is implicated in cerebral dysfunction. Murici (Byrsonimacrassifolia (L.) Kunth) is a fruit rich in antioxidant compounds, which could be an alternative to prevent damage to tissues induced by sepsis. Here, we evaluated the effects of sepsis on the propagation of cortical spreading depression (CSD) and oxidative stress, and tested the action of murici antioxidant extract in prevention against the effect of sepsis. Male Wistar rats (90-210 days, n = 40) were previously supplemented, orogastrically, with murici extract (150 mg/kg/day or 300 mg/kg/day), or an equivalent volume of the vehicle solution, for fifteen days. Then the animals were subjected to experimental sepsis through cecal ligation and perforation (CLP). Subsequently, CSD recordings were obtained and brain oxidative stress was evaluated. Sepsis decelerated CSD and increased the malondialdehyde (MDA) levels in the brain cortex of the animals. In contrast, septic rats that had been previously supplemented with murici antioxidant extract in doses of 150 and 300 mg/kg/day showed an increase in CSD propagation velocity, low levels of MDA and GSH/GSSG ratio and an increase of superoxide dismutase (SOD) activity, regardless of the dose tested. Our results demonstrate that sepsis affects brain excitability and that this effect can be prevented by murici antioxidant extract. The effects of sepsis and/or murici extract on CSD may be due to the oxidative state of the brain.

KEYWORDS:

• Sepsis
• cortical spreading depression
• murici
• oxidative stress

Acknowledgements

The authors thank the Brazilian agency CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) for financial support and CETENE (Centro de Tecnologias Estratégicas do Nordeste) for help in obtaining the extracts. The English text of this paper was revised by Sidney Pratt, Canadian, MAT (The Johns Hopkins University), RSAdip - TESL (Cambridge University).

M.S.B.S.: execution of the experiments, data analysis and writing of the manuscript; D.V.S.A. and H.M.C.M.: help in the execution of the experiments; D.A.G. and E.C.L.: help in sepsis procedures; A.A.S.: designing of the experiments, data analysis and help in the writing of the manuscript.

Ethics approval

All experimental procedures were previously approved by the Institutional Ethics Committee for Animal Research of our University (Approval protocol no. 23076.020868/2014-51), whose norms comply with those established by the National Institutes of Health Guide for Care and Use of Laboratory Animals (Bethesda, MD, USA).

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco [FACEPE, APQ-0484- 2.07/15]. Pro-reitoria de Pesquisa da Universidade Federal de Pernambuco [PROPESQ/UFPE, 23076.048111/2014-22].