RESUMO
Although numerous inflammation pathways have been implicated in Alzheimer's disease, the involvement of the kallikrein-kinin system is still under investigation. We anatomically localized and quantified the density of kinin B(1) and B(2) receptors binding sites in the rat brain after the infusion of amyloid-beta (Abeta) peptide in the right lateral brain ventricle for 5 weeks. The conditioned avoidance test showed a significant reduction of memory consolidation in rats infused with Abeta (68.6+/-20.9%, P<0.05) when compared to control group (90.8+/-4.1%; infused with vehicle). Autoradiographic studies performed in brain samples of both groups using [(125)I]HPP-[des-Arg(10)]-Hoe-140 (150pM, 90min, 25 degrees C) showed a significant increase in density of B(1) receptor binding sites in the ventral hippocampal commissure (1.23+/-0.07fmol/mg), fimbria (1.31+/-0.05fmol/mg), CA1 and CA3 hippocampal areas (1.05+/-0.03 and 1.24+/-0.02fmol/mg, respectively), habenular nuclei (1.30+/-0.04fmol/mg), optical tract (1.30+/-0.05fmol/mg) and internal capsule (1.26+/-0.05fmol/mg) in Abeta group. For B(2) receptors ([(125)I]HPP-Hoe-140, 200pM, 90min, 25 degrees C), a significant increase in density of binding sites was observed in optical tract (2.04+/-0.08fmol/mg), basal nucleus of Meynert (1.84+/-0.18fmol/mg), lateral septal nucleus - dorsal and intermediary portions (1.66+/-0.29fmol/mg), internal capsule (1.74+/-0.19fmol/mg) and habenular nuclei (1.68+/-0.11fmol/mg). In control group, none of these nuclei showed [(125)I]HPP-Hoe-140 labeling. This significant increase in densities of kinin B(1) and B(2) receptors in animals submitted to Abeta infusion was observed mainly in brain regions related to cognitive behavior, suggesting the involvement of the kallikrein-kinin system in Alzheimer's disease in vivo.
Assuntos
Peptídeos beta-Amiloides/administração & dosagem , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Fragmentos de Peptídeos/administração & dosagem , Receptor B1 da Bradicinina/metabolismo , Receptor B2 da Bradicinina/metabolismo , Animais , Sítios de Ligação/efeitos dos fármacos , Infusões Parenterais , Masculino , Ligação Proteica/efeitos dos fármacos , Ratos , Ratos Wistar , Distribuição TecidualRESUMO
There are controversies about the fate of penetrating diaphragmatic injuries not diagnosed and treated. The objective was to evaluate the evolution of untreated diaphragmatic injury on an experimental model. Fifty-six rats suffered diaphragmatic injuries. Two groups were submitted to sternotomy and laparotomy--A (at 11-60 days) and B (at 120-160 days)--and all animals underwent diaphragm anatomopathologic analysis. The macroscopic results revealed diaphragmatic hernia in five animals (8.9%). Our results showed that histologic response was not the factor for this occurrence. We conclude that spontaneous healing of diaphragmatic injury occurs naturally.