HOE-140, an antagonist of [B.sub.2] receptor, protects against memory deficits and brain damage induced by moderate lateral fluid percussion injury in mice

• Published in: Psychopharmacology 2014-05, Vol.231 (9), p.1935
• Main Authors: Ferreira, Ana Paula Oliveira, Rodrigues, Fernanda Silva, Della-Pace, Iuri Domingues, Mota, Bibiana Castagna, Oliveira, Sara Marchesan, de Campos Velho Gewehr, Camila, Bobinski, Franciane, de Oliveira, Clarissa Vasconcelos, Brum, Juliana Sperotto, Oliveira, Mauro Schneider, Furian, Ana Flavia, de Barros, Claudio Severo Lombardo, Santos, Adair Roberto Soares dos, Ferreira, Juliano, Fighera, Michele Rechia, Royes, Luiz Fernando Freire
• Format: Article
• Language: English
• Subjects: Brain; Central nervous system agents; Complications and side effects; Dosage and administration; Genetic aspects; Injuries; Kinins; Physiological aspects
• ISSN: 0033-3158
• DOI: 10.1007/s00213-013-3336-x

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 [B.sub.1]([B.sub.1]R) and [B.sub.2]([B.sub.2]R) on the behavioral, biochemical, and histologic features elicited by moderate lateral fluid percussion injury (mLFPI) in mice. Methods The role of kinin [B.sub.1] and [B.sub.2] receptors in brain damage, neuromotor, and cognitive deficits induced by mLFPI, was evaluated by means of subcutaneous injection of [B.sub.2]R antagonist (HOE-140; 1 or 10 nmol/kg) or [B.sub.1]R-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-1|3, tumor necrosis factor-a, 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.sup.+] [K.sup.+] 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 [B.sub.2] receptor in memory deficits and brain damage caused by mLFPI in mice. Keywords Traumatic brain injury * Bradykinin * Inflammation * Object recognition task * Oxidative stress