Microglia, the resident CNS macrophages, have been implicated in the pathogenesis of Rett Syndrome (RTT), an X-linked neurodevelopmental disorder. However, the mechanism by which microglia contribute to the disorder is unclear and recent data suggest that microglia do not play a causative role. Here, we use the retinogeniculate system to determine if and how microglia contribute to pathogenesis in a RTT mouse model, the Mecp2 null mouse (Mecp2tm1.1Bird/y). We demonstrate that microglia contribute to pathogenesis by excessively engulfing, thereby eliminating, presynaptic inputs at end stages of disease (≥P56 Mecp2 null mice) concomitant with synapse loss. Furthermore, loss or gain of Mecp2 expression specifically in microglia (Cx3cr1CreER;Mecp2fl/yor Cx3cr1CreER; Mecp2LSL/y) had little effect on excessive engulfment, synapse loss, or phenotypic abnormalities. Taken together, our data suggest that microglia contribute to end stages of disease by dismantling neural circuits rendered vulnerable by loss of Mecp2 in other CNS cell types.DOI: http://dx.doi.org/10.7554/eLife.15224.001

Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been shown to be a viable and effective treatment for patients suffering from refractory cardiogenic shock (rCS), which is associated with high mortality rates. Although ECMO therapy used as short-term mechanical circulatory support (MCS) has shown tremendous growth in its application over the past decade, the complication and mortality rates remain high. This retrospective study analyzes complications associated with VA-ECMO support, evaluates the use of defined protocols at a single center, and examines factors that may contribute to patient complication and mortality. Methods: This retrospective analysis included 184 patients who were supported with ECMO from September 2014 through March 2018 at Integris Baptist Medical Center (IBMC). Descriptive statistics were generated to analyze baseline characteristics, demographics, complications, and outcomes. Results: Acute myocardial infarct (AMI) was the primary etiology of this cohort (N=40; 22%). The mean age was 55±15 (median 56, range 15-84) years. All patients were inotrope and/or vasopressor dependent prior to ECMO initiation. Mean time on ECMO support was 7.8±7.9 days with median time of 6 days. Total patient days on support were 1,430. Most ECMO cannulations, 97 (52%) were performed within Integris Baptist Medical Center, with 48% done outside the hospital; 38% were performed outside of the hospital by the IBMC ECMO team, and 10.5% were performed by an outside team. Bleeding was noted to be the most common VA ECMO complication [N=41; 22.3%; 0.028 events per patient day (EPPD)]. Conclusions: A dedicated 24/7 ECMO service using a multidisciplinary team (MDT) and defined protocols in a single center is able to effectively reduce complications due to VA-ECMO support in the sickest of the sick VA-ECMO patients.

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