RESUMEN

Isoflurane-induced neurocognitive impairment in the developing rodent brain is well documented, and regular physical exercise has been demonstrated to be a viable intervention for some types of neurocognitive impairment. This study was designed to investigate the potential protective effect of swimming exercise on both neurocognitive impairment caused by repeated neonatal exposure to isoflurane and the underlying molecular mechanism. Mice received 0.75% isoflurane exposures for 4h on postnatal days 7, 8, and 9. From the third month after anesthesia, the mice were subjected to regular swimming exercise for 4weeks, followed by a contextual fear condition (CFC) trial. We found that repeated neonatal exposure to isoflurane reduced freezing behavior during CFC testing and deregulated hippocampal histone H4K12 acetylation. Conversely, mice subjected to regular swimming exercise showed enhanced hippocampal H3K9, H4K5, and H4K12 acetylation levels, increased numbers of c-Fos-positive cells 1h after CFC training, and less isoflurane-induced memory impairment. We also observed increases in histone acetylation and of cAMP-response element-binding protein (CREB)-binding protein (CBP) during the swimming exercise program. The results suggest that neonatal isoflurane exposure-induced memory impairment was associated with dysregulation of H4K12 acetylation, which may lead to less hippocampal activation following learning tasks. Swimming exercise was associated with enhanced hippocampal histone acetylation and CBP expression. Exercise most likely ameliorated isoflurane-induced memory impairment by enhancing hippocampal histone acetylation and activating more neuron cells during memory formation.

Asunto(s)

Anestésicos/toxicidad , Trastornos del Conocimiento/terapia , Terapia por Ejercicio , Hipocampo/metabolismo , Histonas/metabolismo , Isoflurano/toxicidad , Natación/fisiología , Acetilación/efectos de los fármacos , Animales , Animales Recién Nacidos , Glucemia/efectos de los fármacos , Trastornos del Conocimiento/inducido químicamente , Trastornos del Conocimiento/patología , Trastornos del Conocimiento/rehabilitación , Modelos Animales de Enfermedad , Conducta Exploratoria/efectos de los fármacos , Masculino , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Fosfoproteínas/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Factores de Tiempo , Regulación hacia Arriba/efectos de los fármacos

RESUMEN

Integrin α4ß7 controls lymphocyte trafficking into the gut and has essential roles in inflammatory bowel disease (IBD). The α4ß7-blocking antibody vedolizumab is approved for IBD treatment; however, high dose of vedolizumab aggravates colitis in a small percentage of patients. Herein, we show that integrin ß7 deficiency results in colonic regulatory T (Treg) cell depletion and exacerbates dextran sulfate sodium (DSS) colitis by evoking aberrant innate immunity. In DSS-treated ß7-deficient mice, the loss of colonic Treg cells induces excessive macrophage infiltration in the colon via upregulation of colonic epithelial intercellular adhesion molecule 1 and increases proinflammatory cytokine expression, thereby exacerbating DSS-induced colitis. Moreover, reconstitution of the colonic Treg cell population in ß7-deficient mice suppresses aberrant innate immune response in the colon and attenuates DSS colitis. Thus, integrin α4ß7 is essential for suppression of DSS colitis as it regulates the colonic Treg cell population and innate immunity.

Asunto(s)

Colitis/inmunología , Inmunidad Innata , Inmunidad Mucosa , Integrinas/inmunología , Mucosa Intestinal/inmunología , Linfocitos T Reguladores/inmunología , Animales , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Neutralizantes/farmacología , Movimiento Celular , Colitis/inducido químicamente , Colitis/genética , Colitis/patología , Colon/inmunología , Colon/patología , Sulfato de Dextran , Células Epiteliales/inmunología , Células Epiteliales/patología , Femenino , Regulación de la Expresión Génica , Integrinas/antagonistas & inhibidores , Integrinas/deficiencia , Integrinas/genética , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/inmunología , Mucosa Intestinal/patología , Recuento de Linfocitos , Macrófagos/inmunología , Macrófagos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Transducción de Señal , Linfocitos T Reguladores/patología

RESUMEN

The generation of acoustic waves by a line-focused laser pulse in an optically absorptive cylinder is studied experimentally and theoretically. Experiments are performed on a 5 mm diameter NG5 colored glass rod using Nd:yttrium aluminum garnet laser, which delivers 5 ns pulses. The numerical simulation is based on the semi-analytical model of a radially distributed thermoelastic source, which takes into account penetration of laser energy into the bulk of the sample. Good agreement between the experimental and calculated wave forms is observed. Comparison of these wave forms with an auxiliary simulation, which assumes the model of a dipole source located at the cylinder surface, reveals the effect of optical penetration on the shape of the wave form and also on the relative amplitude of bulk and surface waves.

RESUMEN

A point source-point receiver technique, based on laser generation and laser detection of acoustic waves, allows determination of mechanical properties of an anisotropic cylinder. The nature of the material and the geometry of the sample give a dispersive behaviour to the diffracted waves and make the acoustic signature difficult to interpret. To overpass the intricacies, wave fronts (conical waves in the volume and helical waves on the surface) are synthesized from signals provided by scanning the primitive line of the cylinder with a laser point source. In order to distinguish between direct bulk conical waves and other contributions in the acoustic response, some considerations on line surface waves and on reflected bulk conical waves are supplied. The identification of the stiffness tensor components, based on the inversion of the bulk waves phase velocities, is applied to signals simulated for a composite material.