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HOE-140, an Antagonist of B2 Receptor, Protects Against Memory Deficits and Brain Damage Induced by Moderate Lateral Fluid Percussion Injury in Mice

HOE-140, an Antagonist of B2 Receptor, Protects Against Memory Deficits and Brain Damage Induced by Moderate Lateral Fluid Percussion Injury in Mice

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, etc.

Psychopharmacology (Berl). 2014 May;231(9):1935-48.

PMID: 24202114

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP138614309	HOE 140		138614-30-9	Price

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