RESUMEN
Cerebral ischemic stroke is one of the leading causes of death and disability worldwide, and the only available drug treatment is limited to a short window following the ischemic event. Gastrodin is the major bioactive constituent extracted from thetuberGastrodia elata, and is currently used to treat dizziness in the clinic. "Early" application of gastrodin (before modeling or immediately after ischemic injury) has shown antioxidative and neuroprotective effects in a transient focal brain ischemia model in rodents; however, it is not known whether the delayed administration of gastrodin after permanent focal cerebral ischemia ameliorates neural injury and increases neurogenesis. In this study, we performed a permanent middle cerebral artery occlusion (MCAO) model for the study of cerebral ischemic stroke in adult male mice to examine the effects of gastrodin. Gastrodin treatment that was started "late" (one day after the ischemic injury) significantly improved neural function, reduced infarct volume and apoptosis, and increased the number of DCX/BrdU double-positive cells in permanent MCAO mice. Moreover, gastrodin treatment markedly preserved the Wnt/ß-Catenin signaling pathway, which could promote neurogenesis and provide neuroprotection brain injury. Our findings suggest that gastrodin treatment following ischemic injury can induce neuroprotection, promote neurogenesis and restored the Wnt /ß-Catenin signaling pathway.
Asunto(s)
Alcoholes Bencílicos/farmacología , Isquemia Encefálica/tratamiento farmacológico , Glucósidos/farmacología , Animales , Apoptosis/efectos de los fármacos , Alcoholes Bencílicos/metabolismo , Encéfalo/metabolismo , Isquemia Encefálica/fisiopatología , Modelos Animales de Enfermedad , Proteína Doblecortina , Glucósidos/metabolismo , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Isquemia/tratamiento farmacológico , Masculino , Ratones , Ratones Endogámicos C57BL , Neurogénesis/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/fisiopatología , Vía de Señalización Wnt/efectos de los fármacos , beta Catenina/metabolismoRESUMEN
Neurogenesis correlates closely with the recovery of neural function after brain ischemia but the critical proteins and signaling pathways involved remain unclear. The phosphatase WIP1 has been shown to regulate neurogenesis in models of aging. However, it is not known if WIP1 affects neurogenesis and functional recovery after brain ischemia. To explore these questions, we performed permanent middle cerebral artery occlusion (MCAO) in mice and performed BrdU labeling, neurobehavioral testing, western blotting, and immunofluorescence staining. We found that ischemia induced WIP1 expression in the area bordering the injury. Compared to wild-type mice, the knockout of the Wip1 gene inhibited neurological functional recovery, reduced the expression of doublecortin, and inactivated the Wnt/ß-Catenin signaling pathway in cerebral ischemia in mice. Pharmacological activation of the Wnt/ß-Catenin signaling pathway compensated for the Wip1 knockout-induced deficit in neuroblast formation in animals with MCAO. These findings indicate that WIP1 is essential for neurogenesis after brain injury by activating the Wnt/ß-Catenin signaling pathway.
Asunto(s)
Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Neurogénesis/genética , Proteína Fosfatasa 2C/deficiencia , Vía de Señalización Wnt/genética , beta Catenina/metabolismo , Animales , Infarto Encefálico/etiología , Bromodesoxiuridina/metabolismo , Modelos Animales de Enfermedad , Proteínas de Dominio Doblecortina , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Regulación de la Expresión Génica/genética , Etiquetado Corte-Fin in Situ , Indoles/farmacología , Indoles/uso terapéutico , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Masculino , Maleimidas/farmacología , Maleimidas/uso terapéutico , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas Asociadas a Microtúbulos/metabolismo , Neurogénesis/efectos de los fármacos , Neuropéptidos/metabolismo , Proteína Fosfatasa 2C/genética , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Vía de Señalización Wnt/efectos de los fármacosRESUMEN
To investigate the possible biochemical metabolisms for excess phosphate uptake in a sequencing batch reactor (SBR) with single-stage oxic process, which was reported using glucose as the sole carbon source previously, glucose and acetate were fed to two SBRs as the sole carbon source, respectively. The changes of polyhydroxyalkanoates (PHAs), glycogen and the removal of phosphorus were compared between two SBRs. It was observed that the phosphorus removal efficiency was 91.8-94.4% with glucose, and 23.3-28.5% with acetate, although the former showed much lower accumulations/transformations of PHAs. Instead, the former showed a much higher transformation of glycogen. The facts suggested that glycogen could replace PHAs to supply energy for phosphate uptake under the single-stage oxic condition. Furthermore, the possible biochemical metabolisms were proposed to describe the relation between phosphate uptake and energy storages formations under such a single-stage oxic process. Such a process may serve as a prototype for the development of alternative biological and chemical options for phosphate removal from wastewaters.