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Background and purpose: Stroke is a major cause of neonatal morbidity, often with delayed diagnosis and with no accepted therapeutic options. The purpose of this study is to investigate the efficacy of delayed initiation of multiple dose erythropoietin (EPO) therapy in improving histological and behavioral outcomes after early transient ischemic stroke. Methods: 32 postnatal day 10 (P10) Sprague-Dawley rats underwent sham surgery or transient middle cerebral artery occlusion (tMCAO) for 3 h, resulting in injury involving the striatum and parieto-temporal cortex. EPO (1000 U/kg per dose × 3 doses) or vehicle was administered intraperitoneally starting one week after tMCAO (at P17, P20, and P23). At four weeks after tMCAO, sensorimotor function was assessed in these four groups (6 vehicle-sham, 6 EPO-sham, 10 vehicle-tMCAO and 10 EPO-tMCAO) with forepaw preference in cylinder rearing trials. Brains were then harvested for hemispheric volume and Western blot analysis. Results: EPO-tMCAO animals had significant improvement in forepaw symmetry in cylinder rearing trials compared to vehicle-tMCAO animals, and did not differ from sham animals. There was also significant preservation of hemispheric brain volume in EPO-tMCAO compared to vehicle-tMCAO animals. No differences in ongoing cell death at P17 or P24 were noted by spectrin cleavage in either EPO-tMCAO or vehicle-tMCAO groups. Conclusions: These results suggest that delayed EPO therapy improves both behavioral and histological outcomes at one month following transient neonatal stroke, and may provide a late treatment alternative for early brain injury.

In recent years, growth factor therapy has emerged as a potential treatment for ischemic brain injury. The efficacy of therapies that either directly introduce or stimulate local production of growth factors and their receptors in damaged brain tissue has been tested in a multitude of models for different Central Nervous System (CNS) diseases. These growth factors include erythropoietin (EPO), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and insulin-like growth factor (IGF-1), among others. Despite the promise shown in animal models, the particular growth factors that should be used to maximize both brain protection and repair, and the therapeutic critical period, are not well defined. We will review current pre-clinical and clinical evidence for growth factor therapies in treating different causes of brain injury, as well as issues to be addressed prior to application in humans.

As the resident macrophages of the brain and spinal cord, microglia are crucial for the phagocytosis of infectious agents, apoptotic cells and synapses. During brain injury or infection, bone-marrow derived macrophages invade neural tissue, making it difficult to distinguish between invading macrophages and resident microglia. In addition to circulation-derived monocytes, other non-microglial central nervous system (CNS) macrophage subtypes include border-associated meningeal, perivascular and choroid plexus macrophages. Using immunofluorescent labeling, flow cytometry and Cre-dependent ribosomal immunoprecipitations, we describe P2ry12-CreER, a new tool for the genetic targeting of microglia. We use this new tool to track microglia during embryonic development and in the context of ischemic injury and neuroinflammation. Because of the specificity and robustness of microglial recombination with P2ry12-CreER, we believe that this new mouse line will be particularly useful for future studies of microglial function in development and disease.

Introducción: La derivación porto-cava transitoria es un procedimiento quirúrgico cuyas ventajas en el trasplante hepático aun se discuten. Objetivos: Identificar la influencia de la derivación porto-cava transitoria en 11 variables intraoperatorias. Método: aleatoriamente 37 pacientes cirróticos enlistados para TH primario con preservación de la cava, ingresaron en dos posibles grupos: Sin derivación (SD) (n=18) sin derivación porto-cava transitoria y con n derivación (CD) (n=19) con DPT. Variables: índice cardiaco (IC), presión capilar pulmonar (PCP), presión venosa central (PVC), resistencia vascular sistémica (RVS) porcentaje de saturación de la hemoglobina en sangre venosa mezclada (SvO2), gasto urinario (GU) potasio sérico (KS), bicarbonato sérico (BS), transfusión de hematíes (UCH), tiempo quirúrgico (TQ) y ocurrencia del síndrome de reperfusión (SRP), medidos en momentos cruciales y contrastables. Para las variables demográficas y el SRP se utilizó la prueba Chi2 y para comparar medias, la prueba de Mann-Whitney. Significación: pResultados: No hubo diferencias significativas entre las variables demográficas ni en los valores basales. Treinta minutos después de haber cerrado la porta en SD o 15 minutos después de finalizar la derivación porto cava PT en CD, el IC, la PCP, la PVC, el GU, la SvO2 y el BS fueron significativamente menores en el grupo SD; (pConclusiones: En este estudio la DPT tuvo una influencia favorable al reducir los peligros y la morbilidad intraoperatoria del TH.

Introducción: La derivación porto-cava transitoria es un procedimiento quirúrgico cuyas ventajas en el trasplante hepático aun se discuten. Objetivos: Identificar la influencia de la derivación porto-cava transitoria en 11 variables intraoperatorias. Método: aleatoriamente 37 pacientes cirróticos enlistados para TH primario con preservación de la cava, ingresaron en dos posibles grupos: Sin derivación (SD) (n=18) sin derivación porto-cava transitoria y con n derivación (CD) (n=19) con DPT. Variables: índice cardiaco (IC), presión capilar pulmonar (PCP), presión venosa central (PVC), resistencia vascular sistémica (RVS) porcentaje de saturación de la hemoglobina en sangre venosa mezclada (SvO2), gasto urinario (GU) potasio sérico (KS), bicarbonato sérico (BS), transfusión de hematíes (UCH), tiempo quirúrgico (TQ) y ocurrencia del síndrome de reperfusión (SRP), medidos en momentos cruciales y contrastables. Para las variables demográficas y el SRP se utilizó la prueba Chi2 y para comparar medias, la prueba de Mann-Whitney. Significación: pResultados: No hubo diferencias significativas entre las variables demográficas ni en los valores basales. Treinta minutos después de haber cerrado la porta en SD o 15 minutos después de finalizar la derivación porto cava PT en CD, el IC, la PCP, la PVC, el GU, la SvO2 y el BS fueron significativamente menores en el grupo SD; (pConclusiones: En este estudio la DPT tuvo una influencia favorable al reducir los peligros y la morbilidad intraoperatoria del TH.