RESUMEN
Microelectrode implants are an important tool in neuroscience research and in developing brainâ»machine interfaces. Data from rodents have consistently shown that astrocytes are recruited to the area surrounding implants, forming a glial scar that increases electrode impedance and reduces chronic utility. However, studies in non-human primates are scarce, with none to date in marmosets. We used glial fibrillary acidic protein (GFAP) immunostaining to characterize the acute and chronic response of the marmoset brain to microelectrodes. By using densitometry, we showed that marmoset astrocytes surround brain implants and that a glial scar is formed over time, with significant increase in the chronic condition relative to the acute condition animal.
RESUMEN
Hepatic stellate cells (HSC) play a key role in liver fibrogenesis. Activation of PPARγ and inhibition of fibrogenic molecules are potential strategies to block HSC activation and differentiation. Aware that the process of hepatic fibrosis involves inflammatory mediators, various anti-inflammatory substances have been studied in an attempt to revert fibrosis. The purpose of this study was to investigate the in vitro effects of fructose-1,6-bisphosphate (FBP) on HSC phenotype reversion. The results demonstrated that FBP induced quiescent phenotype in GRX cells via PPARγ activation. Significant decrease in type I collagen mRNA expression was observed in the first 24h of treatment. These events preceded the reduction of TGF-ß1 and total collagen secretion. Thus, FBP promoted downregulation of HSC activation by its antifibrotic action. These findings demonstrate that FBP may have potential as a novel therapeutic agent for the treatment of liver fibrosis.
Asunto(s)
Fructosadifosfatos/farmacología , Células Estrelladas Hepáticas/efectos de los fármacos , PPAR gamma/genética , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Colágeno/genética , Colágeno/metabolismo , Fibrosis/tratamiento farmacológico , Células Estrelladas Hepáticas/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Ratones , ARN Mensajero/metabolismo , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Hepatic stellate cells (HSC) play a key role in liver fibrogenesis. Activation of PPARγ and inhibition of fibrogenic molecules are potential strategies to block HSC activation and differentiation. A number of natural products have been suggested to have antifibrotic effects for the de-activation and de-differentiation of HSCs. The purpose of this study was to investigate the in vitro effects of capsaicin on HSC de-activation and de-differentiation. The results demonstrated that capsaicin induced quiescent phenotype in GRX via PPARγ activation. Significant decrease in COX-2 and type I collagen mRNA expression was observed in the first 24 h of treatment. These events preceded the reduction of TGF-ß1 and total collagen secretion. Thus, capsaicin promoted down-regulation of HSC activation by its antifibrotic and anti-inflammatory actions. These findings demonstrate that capsaicin may have potential as a novel therapeutic agent for the treatment of liver fibrosis.
Asunto(s)
Capsaicina/farmacología , Diferenciación Celular , Células Estrelladas Hepáticas/citología , Animales , Antiinflamatorios/farmacología , Células Cultivadas , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Regulación hacia Abajo , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , PPAR gamma/genética , PPAR gamma/metabolismo , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
The aim of this study was to test the hypothesis that the renin-angiotensin system (RAS) components, as well as the oxidative stress system, would respond to early environmental changes. Thus, we have evaluated the effects of neonatal handling on both brain and kidney RAS and oxidative stress. Pups were divided into two groups: nonhandled and handled. The procedure consisted of handling them for 1 min/day in the first 10 days of life. On days 1, 5, and 10, animals were killed by decapitation. Blood samples were collected and the brain and kidneys were removed. Renin, AT(1), and AT(2) mRNA expression were evaluated through RT-PCR. Angiotensin II (ANG II) serum concentration was also measured. An increased ANG II concentration, brain and kidney AT(2) mRNA expression were demonstrated. The kidney mRNA AT(1) expression was decreased. There was also a kidney lipid peroxidation increase and a brain superoxide dismutase and catalase decrease. In conclusion, handling in the neonatal period induces the activation of the angiotensinergic system, as well as modulates its mRNA receptor expression. The oxidative stress balance system seems not to be involved.
