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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Acknowledgments
The presente study was supported by Conselho Nacional de Desenvolvimento Científico (CNPq) and by Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES; Brazil). Ferreira J is the recipient of CNPq fellowships, grant numbers 301552/2007-0. Royes L.F.F is recipient of CNPq/FAPERGS fellowships, grant numbers 11/2082-4. The funding sources had no involvement in study design, in the collection, analysis, interpretation of data, and in the writing of the report. We also attest that all the experimentswere performed in compliance with Brazilian (law no. 6638 of 1979—Standards for the Practice Teaching-scientific Animal use) law currently in force, and that experiments were previously approved by the Committee on the Use and Care of Laboratory Animals of the Federal University of the Santa Maria (process number: 113/2010).
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Ferreira, A.P.O., Rodrigues, F.S., Della-Pace, I.D. et al. HOE-140, an antagonist of B2 receptor, protects against memory deficits and brain damage induced by moderate lateral fluid percussion injury in mice. Psychopharmacology 231, 1935–1948 (2014). https://doi.org/10.1007/s00213-013-3336-x
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DOI: https://doi.org/10.1007/s00213-013-3336-x