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Repetitive synaptic stimulation can induce different forms of synaptic plasticity but may also limit the robustness of synaptic transmission by exhausting key resources. Little is known about how synaptic transmission is stabilized after high-frequency stimulation. In the present study, we observed that tetanic stimulation of the Drosophila neuromuscular junction (NMJ) decreases quantal content, release-ready vesicle pool size and synaptic vesicle density for minutes after stimulation. This was accompanied by a pronounced increase in quantal size. Interestingly, action potential-evoked synaptic transmission remained largely unchanged. EPSC amplitude fluctuation analysis confirmed the post-tetanic increase in quantal size and the decrease in quantal content, suggesting that the quantal size increase counteracts release depression to maintain evoked transmission. The magnitude of the post-tetanic quantal size increase and release depression correlated with stimulation frequency and duration, indicating activity-dependent stabilization of synaptic transmission. The post-tetanic quantal size increase persisted after genetic ablation of the glutamate receptor subunits GluRIIA or GluRIIB, and glutamate receptor calcium permeability, as well as blockade of postsynaptic calcium channels. By contrast, it was strongly attenuated by pharmacological or presynaptic genetic perturbation of the GTPase dynamin. Similar observations were made after inhibition of the H+-ATPase, suggesting that the quantal size increase is presynaptically driven. Additionally, dynamin and H+-ATPase perturbation resulted in a post-tetanic decrease in evoked amplitudes. Finally, we observed an increase in synaptic vesicle diameter after tetanic stimulation. Thus, a presynaptically-driven quantal size increase, likely mediated by larger synaptic vesicles, counterbalances post-tetanic release depression, thereby conferring robustness to synaptic transmission on the minute time scale. KEY POINTS: Many synapses transmit robustly after sustained activity despite the limitation of key resources, such as release-ready synaptic vesicles. We report robust synaptic transmission after sustained high-frequency stimulation of the Drosophila neuromuscular junction despite a reduction in release-ready vesicle number. An increased postsynaptic response to individual vesicles, likely driven by an increase in vesicle size due to endocytosis defects, stabilizes synaptic efficacy for minutes after sustained activity. Our study provides novel insights into the mechanisms governing synaptic stability after sustained neural activity.
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Mature astrocytes become activated upon non-specific tissue damage and contribute to glial scar formation. Proliferation and migration of adult reactive astrocytes after injury is considered very limited. However, the regenerative behavior of individual astrocytes following selective astroglial loss, as seen in astrocytopathies, such as neuromyelitis optica spectrum disorder, remains unexplored. Here, we performed longitudinal in vivo imaging of cortical astrocytes after focal astrocyte ablation in mice. We discovered that perilesional astrocytes develop a remarkable plasticity for efficient lesion repopulation. A subset of mature astrocytes transforms into reactive progenitor-like (REPL) astrocytes that not only undergo multiple asymmetric divisions but also remain in a multinucleated interstage. This regenerative response facilitates efficient migration of newly formed daughter cell nuclei towards unoccupied astrocyte territories. Our findings define the cellular principles of astrocyte plasticity upon focal lesion, unravelling the REPL phenotype as a fundamental regenerative strategy of mature astrocytes to restore astrocytic networks in the adult mammalian brain. Promoting this regenerative phenotype bears therapeutic potential for neurological conditions involving glial dysfunction.
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Aortitis is an infrequent cause of aortic root dilatation and aortic valve regurgitation. Valve-sparing procedures have been proposed, but there is not clear evidence of which is the treatment of choice. We report the case of a 38-year-old pregnant lady with a diagnosis of idiopathic aortitis associated with aortic root aneurysm and severe aortic valve regurgitation.
Assuntos
Carcinoma de Células Gigantes/patologia , Neoplasias Renais/patologia , Artéria Pulmonar/patologia , Neoplasias Vasculares/patologia , Carcinoma de Células Gigantes/cirurgia , Constrição Patológica/patologia , Ecocardiografia Transesofagiana , Humanos , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Tomografia Computadorizada por Raios X , Neoplasias Vasculares/cirurgiaRESUMO
The U-Clip (Coalescent Surgical, Sunnydale, CA USA) allows the surgeon to create an interrupted anastomosis in the same amount of time that is required for a continuous anastomosis with the elimination of knotting. Its use is indicated especially in minimally invasive surgery. We describe a case of a patient in which the proximal anastomosis was performed by interrupted suture with Coalescent U-Clip anastomotic device. Six months later, he presented with stenosis of the anastomosis, and intravascular ultrasound showed anastomotic neointimal hyperplasia.
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INTRODUCTION: In order to improve the prognosis, repair of severe mitral regurgitation should be undertaken at the same time as aortic valve replacement in patients with severe aortic valve stenosis. However, mitral regurgitation may be secondary to pressure overload or ventricular dysfunction and improve after surgery. AIM: To assess the incidence of non-severe functional mitral regurgitation before and after isolated aortic valve replacement and determine its influence on the postoperative course. METHODS: The clinical and surgical characteristics were compared in a cohort of 577 consecutive patients who underwent isolated aortic valve replacement. RESULTS: The mean age was 68.4+/-9.2 years (44% women). Non-severe functional mitral valve regurgitation was detected prior to surgery in 26.5% of the patients. These patients were older (p=0.009), more often had ventricular dysfunction (p=0.005) and pulmonary hypertension (0.002), and had been admitted more frequently for heart failure (0.002), with fewer of them conserving sinus rhythm (p<0.001). Additionally, the pre-surgery existence of mitral regurgitation was associated with greater morbidity and mortality (10.5% vs 5.6%; p=0.025). The mitral regurgitation disappeared or improved prior to hospital discharge in 56.2% and 15.6%, respectively. Independent factors predicting this improvement were the presence of coronary lesions (OR 3.7, p=0.038), and the absence of diabetes (OR 0.28, p=0.011) and pulmonary hypertension (0.33, p=0.046). CONCLUSIONS: The presence of intermediate degree mitral regurgitation in patients undergoing isolated aortic valve replacement increases morbidity and mortality. However, a high percentage of those who do survive experience disappearance or improvement of the mitral regurgitation.