RESUMEN
Glucose hypometabolism in cortical structures after functional disconnection is frequently reported in patients with white matter diseases such as subcortical stroke. However, the molecular and cellular mechanisms have been poorly elucidated. Here we show, in an animal model of internal capsular infarct, that GABA-synthesizing reactive astrocytes in distant cortical areas cause glucose hypometabolism via tonic inhibition of neighboring neurons. We find that reversal of aberrant astrocytic GABA synthesis, by pharmacological inhibition and astrocyte-specific gene silencing of MAO-B, reverses the reduction in cortical glucose metabolism. Moreover, induction of aberrant astrocytic GABA synthesis by cortical injection of putrescine or adenovirus recapitulates cortical hypometabolism. Furthermore, MAO-B inhibition causes a remarkable recovery from post-stroke motor deficits when combined with a rehabilitation regimen. Collectively, our data indicate that cortical glucose hypometabolism in subcortical stroke is caused by aberrant astrocytic GABA and MAO-B inhibition and that attenuating cortical hypometabolism can be a therapeutic approach in subcortical stroke.
Asunto(s)
Astrocitos/metabolismo , Corteza Cerebral/metabolismo , Corteza Cerebral/fisiopatología , Recuperación de la Función , Accidente Cerebrovascular/metabolismo , Accidente Cerebrovascular/fisiopatología , Ácido gamma-Aminobutírico/metabolismo , Animales , Astrocitos/efectos de los fármacos , Astrocitos/patología , Corteza Cerebral/ultraestructura , Glucosa/metabolismo , Masculino , Modelos Biológicos , Monoaminooxidasa/metabolismo , Inhibidores de la Monoaminooxidasa/farmacología , Actividad Motora/efectos de los fármacos , Células Piramidales/metabolismo , Ratas Sprague-Dawley , Recuperación de la Función/efectos de los fármacosRESUMEN
In this paper, we propose an Au-polypyrrole (Ppy) nanorod gas sensor for the detection of volatile organic compound (VOC) gases. This gas sensor operates on the principle of localized surface plasmon resonance (LSPR). The Au-Ppy nanorods used in this experiment were synthesized using an anodic aluminum oxide template by the electrochemical deposition method. Using field emission scanning electron microscopy, we confirmed that the Au-Ppy nanorod arrays were successfully fabricated with a uniform size. By depositing gold, the Au-Ppy nanorods exhibited both optical and LSPR interference. The gas sensing properties of the fabricated nanorods were tested for VOCs such as acetic acid, benzene, and toluene with a short response time (~1 min). Moreover, the proposed VOC gas sensing system was tested with three types of VOC gases over a wide concentration range from 10 to 100 ppm. Highest sensitivity was observed for acetic acid gas, which had a linear relation with the gas concentration, indicating that the system can be used as a gas sensor.