RESUMO
Vision loss is a devastating consequence of systemic hypoxia, but the cellular mechanisms are unclear. We investigated the impact of acute hypoxia in the retina and optic nerve. We induced systemic hypoxia (10% O2) in 6-8w mice for 48 h and performed in vivo imaging using optical coherence tomography (OCT) at baseline and after 48 h to analyze structural changes in the retina and optic nerve. We analyzed glial cellular and molecular changes by histology and immunofluorescence and the impact of pretreatment with 4-phenylbutyric acid (4-PBA) in oligodendroglia survival. After 48 h hypoxia, we found no change in ganglion cell complex thickness and no loss of retinal ganglion cells. Despite this, there was significantly increased expression of CCAAT-enhancer-binding protein homologous protein (CHOP), a marker of endoplasmic reticulum stress, in the retina and optic nerve. In addition, hypoxia induced obvious increase of GFAP expression in the anterior optic nerve, where it co-localized with CHOP, and significant loss of Olig2+ oligodendrocytes. Pretreatment with 4-PBA, which has been shown to reduce endoplasmic reticulum stress, rescued total Olig2+ oligodendrocytes and increased the pool of mature (CC-1+) but not of immature (PDGFRa+) oligodendrocytes. Consistent with a selective vulnerability of the retina and optic nerve in hypoxia, the most striking changes in the 48 h murine model of hypoxia were in glial cells in the optic nerve, including increased CHOP expression in the astrocytes and loss of oligodendrocytes. Our data support a model where glial dysfunction is among the earliest events in systemic hypoxia - suggesting that glia may be a novel target in treatment of hypoxia.
Assuntos
Hipóxia/complicações , Neuroglia/patologia , Doenças do Nervo Óptico/diagnóstico , Nervo Óptico/patologia , Animais , Sobrevivência Celular , Modelos Animais de Doenças , Feminino , Hipóxia/diagnóstico , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Endogâmicos C57BL , Doenças do Nervo Óptico/etiologia , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica/métodosRESUMO
OBJECTIVES: While many U.S. emergency departments (ED) have a "pediatric ED," there are, to our knowledge, no accepted criteria for this type of ED. We investigated the prevalence, distribution, staffing, and characteristics of self-reported pediatric areas in U.S. general EDs. METHODS: We conducted a survey of all 5,273 U.S. EDs to characterize emergency care in 2015. We then surveyed 130 of the 426 general EDs who reported having a pediatric area. Data collection for the second survey included confirmation of a pediatric area and information on that area's structure and staffing. RESULTS: The national survey (85% response) showed 10% of general EDs reported a pediatric area. Only 16% of all U.S. EDs had a pediatric emergency care coordinator (PECC). EDs with larger visit volumes, or in the Northeast or South, were more likely to have a pediatric area. Nine states had no general EDs with pediatric areas. Among general EDs with a pediatric area, 75% had a PECC and 74% had a board-certified or board-eligible pediatric emergency medicine (PEM) physician on staff. Ninety-three percent had designated pediatric beds. Rarely (3%) was the pediatric area just a separate waiting area within a general ED, without any PECC or PEM physician present. CONCLUSIONS: We found that 10% of U.S. general EDs had a pediatric area and that this prevalence varies nationwide. Moreover, only 16% of U.S. EDs had a PECC. Further studies on the impact of ED structure and staffing on pediatric care and patient outcomes are urgently needed. As a long-term objective, a standardized definition of a pediatric ED would not only help quality improvement efforts but also help families make more informed choices about where to bring their children to receive care.