title: HOE-140, an antagonist of B2 receptor, protects against memory deficits and brain damage induced by moderate lateral fluid percussion injury in mice.
abstract: BACKGROUND
  There are evidences indicating the role of kinins in pathophysiology of traumatic brain injury, but little is known about their action on memory deficits.
  
  
  OBJECTIVE
  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.
authors.affiliation: Laboratório de Bioquímica do Exercício, Departamento de Métodos e Técnicas Desportivas, Centro de Educação Física e Desportos, Universidade Federal de Santa Maria (UFSM), 97105-900, Santa Maria, RS, Brasil.
authors.forename: Ana Paula Oliveira
authors.initials: AP
authors.lastname: Ferreira
authors.forename: Fernanda Silva
authors.initials: FS
authors.lastname: Rodrigues
authors.forename: Iuri Domingues
authors.initials: ID
authors.lastname: Della-Pace
authors.forename: Bibiana Castagna
authors.initials: BC
authors.lastname: Mota
authors.forename: Sara Marchesan
authors.initials: SM
authors.lastname: Oliveira
authors.forename: Camila
authors.initials: C
authors.lastname: de Campos Velho Gewehr
authors.forename: Franciane
authors.initials: F
authors.lastname: Bobinski
authors.forename: Clarissa Vasconcelos
authors.initials: CV
authors.lastname: de Oliveira
authors.forename: Juliana Sperotto
authors.initials: JS
authors.lastname: Brum
authors.forename: Mauro Schneider
authors.initials: MS
authors.lastname: Oliveira
authors.forename: Ana Flavia
authors.initials: AF
authors.lastname: Furian
authors.forename: Claudio Severo Lombardo
authors.initials: CS
authors.lastname: de Barros
authors.forename: Adair Roberto Soares
authors.initials: AR
authors.lastname: dos Santos
authors.forename: Juliano
authors.initials: J
authors.lastname: Ferreira
authors.forename: Michele Rechia
authors.initials: MR
authors.lastname: Fighera
authors.forename: Luiz Fernando Freire
authors.initials: LF
authors.lastname: Royes
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D065169:Bradykinin B1 Receptor Antagonists / Q000494:pharmacology; D065094:Bradykinin B2 Receptor Antagonists / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D001930:Brain Injuries / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D019255:NADPH Oxidases / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
chemical_list: D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D018696:Neuroprotective Agents; C051090:bradykinin, Leu(8)-des-Arg(9)-; C065679:icatibant; D019255:NADPH Oxidases; D001920:Bradykinin