HOE-140, an antagonist of B2 receptor,protects against memory deficits and brain damage induced by moderate lateral fluid percussion injury in mice |
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Authors: | Ana Paula Oliveira Ferreira Fernanda Silva Rodrigues Iuri Domingues Della-Pace Bibiana Castagna Mota Sara Marchesan Oliveira Camila de Campos Velho Gewehr Franciane Bobinski Clarissa Vasconcelos de Oliveira Juliana Sperotto Brum Mauro Schneider Oliveira Ana Flavia Furian Claudio Severo Lombardo de Barros Adair Roberto Soares dos Santos Juliano Ferreira Michele Rechia Fighera Luiz Fernando Freire Royes |
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Affiliation: | 1. Laboratório de Bioquímica do Exercício, Departamento de Métodos e Técnicas Desportivas, Centro de Educa??o Física e Desportos, Universidade Federal de Santa Maria (UFSM), 97105-900, Santa Maria, RS, Brasil 2. Programa de Pós—Gradua??o em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil 3. Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianólpolis, SC, Brasil 4. Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil 5. Departamento de Patologia, Centro de Ciências Rurais, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil 6. Departamento de Ciência e Tecnologia de Alimentos, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil 7. Departamento de Neuropsiquiatria, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil
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Abstract: | Rationale There are evidences indicating the role of kinins in pathophysiology of traumatic brain injury, but little is known about their action on memory deficits. Objectives Our aim was to establish the role of bradykinin receptors B1 (B1R) and B2 (B2R) on the behavioral, biochemical, and histologic features elicited by moderate lateral fluid percussion injury (mLFPI) in mice. Methods The role of kinin B1 and B2 receptors in brain damage, neuromotor, and cognitive deficits induced by mLFPI, was evaluated by means of subcutaneous injection of B2R antagonist (HOE-140; 1 or 10 nmol/kg) or B1R antagonist (des-Arg9-[Leu8]-bradykinin (DAL-Bk; 1 or 10 nmol/kg) 30 min and 24 h after brain injury. Brain damage was evaluated in the cortex, being considered as lesion volume, inflammatory, and oxidative damage. The open field and elevated plus maze tests were performed to exclude the nonspecific effects on object recognition memory test. Results Our data revealed that HOE-140 (10 nmol/kg) protected against memory impairment. This treatment attenuated the brain edema, interleukin-1β, tumor necrosis factor-α, and nitric oxide metabolites content elicited by mLFPI. Accordingly, HOE-140 administration protected against the increase of nicotinamide adenine dinucleotide phosphate oxidase activity, thiobarbituric-acid-reactive species, protein carbonylation generation, and Na+ K+ ATPase inhibition induced by trauma. Histologic analysis showed that HOE-140 reduced lesion volume when analyzed 7 days after brain injury. Conclusions This study suggests the involvement of the B2 receptor in memory deficits and brain damage caused by mLFPI in mice. |
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