The subunit composition of postsynaptic non-NMDA-type glutamate receptors (GluRs) determines the function and trafficking of the receptor. Changes in GluR composition have been implicated in the homeostasis of neuronal excitability and synaptic plasticity underlying learning. Here, we imaged GluRs in vivo during the formation of new postsynaptic densities (PSDs) at Drosophila neuromuscular junctions coexpressing GluRIIA and GluRIIB subunits. GluR composition was independently regulated at directly neighboring PSDs on a submicron scale. Immature PSDs typically had large amounts of GluRIIA and small amounts of GluRIIB. During subsequent PSD maturation, however, the GluRIIA/GluRIIB composition changed and became more balanced. Reducing presynaptic glutamate release increased GluRIIA, but decreased GluRIIB incorporation. Moreover, the maturation of GluR composition correlated in a site-specific manner with the level of Bruchpilot, an active zone protein that is essential for mature glutamate release. Thus, we show that an activity-dependent, site-specific control of GluR composition can contribute to match pre- and postsynaptic assembly.
• Collateral flow visibility on CTA strongly depends on the acquisition phase • tMIP offers the best visualisation of the extent of collaterals • Outcome prediction may be better with tMIP than with earlier phases.• Total extent of collaterals seems more important than their filling speed • If triggered too early, CTA may underestimate collateral flow.
BackgroundThe Dystrophin-glycoprotein complex (DGC) comprises dystrophin, dystroglycan, sarcoglycan, dystrobrevin and syntrophin subunits. In muscle fibers, it is thought to provide an essential mechanical link between the intracellular cytoskeleton and the extracellular matrix and to protect the sarcolemma during muscle contraction. Mutations affecting the DGC cause muscular dystrophies. Most members of the DGC are also concentrated at the neuromuscular junction (NMJ), where their deficiency is often associated with NMJ structural defects. Hence, synaptic dysfunction may also intervene in the pathology of dystrophic muscles. Dystroglycan is a central component of the DGC because it establishes a link between the extracellular matrix and Dystrophin. In this study, we focused on the synaptic role of Dystroglycan (Dg) in Drosophila.Methodology/Principal FindingsWe show that Dg was concentrated postsynaptically at the glutamatergic NMJ, where, like in vertebrates, it controls the concentration of synaptic Laminin and Dystrophin homologues. We also found that synaptic Dg controlled the amount of postsynaptic 4.1 protein Coracle and alpha-Spectrin, as well as the relative subunit composition of glutamate receptors. In addition, both Dystrophin and Coracle were required for normal Dg concentration at the synapse. In electrophysiological recordings, loss of postsynaptic Dg did not affect postsynaptic response, but, surprisingly, led to a decrease in glutamate release from the presynaptic site.Conclusion/SignificanceAltogether, our study illustrates a conservation of DGC composition and interactions between Drosophila and vertebrates at the synapse, highlights new proteins associated with this complex and suggests an unsuspected trans-synaptic function of Dg.
Background and Purpose-Patient selection is crucial in the endovascular treatment of acute ischemic stroke patients.Baseline computed tomographic (CT) images, evaluated with the Alberta Stroke Program Early CT Scale (ASPECTS), are considered significant predictors of outcome. In this study, we evaluated CT images and perfusion parameters, analyzed with ASPECTS, as final outcome predictors after endovascular stroke treatment. Methods-We analyzed a cohort of patients with acute ischemic stroke and endovascular treatment. Patients with an occlusion of the M1 segment and multimodal CT imaging were included. CT perfusion data were reconstructed using commercial software. Two experienced neuroradiologists separately reviewed and scored CT and CT perfusion images with the ASPECTS score. Parameters were compared between patients with poor and with favorable follow-up outcome.Significantly different variables were further analyzed by forward stepwise logistic regression. Results-Fifty-one patients were included in our study. Baseline characteristics did not differ between patients with favorable and poor outcomes. No significant difference in recanalization status, the various times, or CT ASPECTS was demonstrated between these 2 groups. Significant differences were demonstrated for age (P=0.0049), cerebral blood volume ASPECTS (P=0.0007), and between cerebral blood volume and cerebral blood flow ASPECTS (P=0.0045).Cerebral blood volume ASPECTS >7 demonstrated the highest sensitivity and specificity for favorable outcome with 84% and 79%, respectively. Conclusions-CT perfusion parameters, evaluated with ASPECTS, are optimal predictors of outcome and are more sensitive and specific than CT ASPECTS in the prediction of favorable outcome. Use of these parameters in treatment decisions could reduce futile recanalizations. (Stroke. 2013;44:2188-2193.)
BACKGROUND AND PURPOSE:As part of a multicenter cooperation (Aneurysm-Like Synthetic bodies for Testing Endovascular devices in 3D Reality) with focus on implementation of additive manufacturing in neuroradiologic practice, we systematically assessed the technical feasibility and accuracy of several additive manufacturing techniques. We evaluated the method of fused deposition modeling for the production of aneurysm models replicating patient-specific anatomy.
Background and Purpose-Multimodal CT imaging consisting of nonenhanced CT, CT angiography (CTA), and whole-brain volume perfusion CT is increasingly used for acute stroke imaging. In these patients, presence of vessel occlusion is an important factor governing treatment decisions and possible endovascular therapy. The goal of this study was to assess the value and diagnostic accuracy of angiographic thin-slice volume perfusion CT reconstructions for the detection of intracranial large vessel occlusion in patients with stroke. Methods-Fifty-eight patients with acute stroke received nonenhanced CT, CTA, and volume perfusion CT. All images were obtained on a 128-slice multidetector CT scanner. CT angiographic axial and coronal maximum-intensity projections of the head were reconstructed from conventional CTA and from the peak arterial scan of the volume perfusion CT data set (4-dimensional CTA). Images were assessed for the presence of intracranial vessel occlusion. The distribution of ischemic lesions was analyzed on perfusion parameter maps. Results-On CTA, 30 patients (52%) had a total of 33 occluded intracranial artery segments. Twenty-eight occlusions were identified on 4-dimensional CTA, resulting in an 85% sensitivity with a positive predictive value of 97%. When combined with an analysis of the perfusion parameter maps, sensitivity of 4-dimensional CTA increased to 94% with a positive predictive value of 100%. Conclusions-In acute stroke, angiographic volume perfusion CT reconstructions may be a feasible option to detect intracranial arterial occlusion and evaluate patients for endovascular therapy. Sensitivity for detection of intracranial arterial occlusion can be increased by simultaneous assessment of perfusion parameter maps. Future studies should assess whether time-resolved 4-dimensional CTA may offer additional diagnostically relevant information compared with single-phase CTA. (Stroke. 2012;43:97-102.)
BACKGROUND AND PURPOSE:In patients with acute stroke, the location and extent of intravascular thrombi correlate with clinical and imaging outcomes and have been used to predict the success of intravenous thrombolysis. We hypothesized that 4D-CTA reconstructed from whole-brain CTP more closely outlines intracranial thrombi than conventional single-phase CTA.
Purpose:To optimize contrast-to-noise and spatial resolution of a FLASH-based magnetization transfer (MT) protocol for visualization of substructures in human thalamus. Materials and Methods:Healthy adults were examined at 3 Tesla with a three-dimensional (3D) spoiled gradient-echo sequence. The signal-to-noise ratio (SNR) was increased by averaging eight bipolar echo acquisitions (mean echo time ϭ 12.3 ms; bandwidth ϭ 370 Hz/pixel). Three isotropic datasets with different weighting (proton density: flip angle/repetition time ϭ 7°/30 ms; T 1 : 20°/30 ms and MT: 10°/48 ms, Gaussian MT prepulse) yielded maps of T 1 , signal amplitude, MT ratio and MT saturation for comparison to MP-RAGE images. Measuring time was 23 min using partial k-space acquisition. First, the SNR of MT saturation maps in thalamus was optimized by means of the excitation flip angle. Then, noise and partial volume effects were traded off by means of the resolution. Finally, the contrast within the thalamus and to adjacent structures was compared between different maps. Results:The optimized MT saturation maps at 0.95 mm isotropic resolution provided the highest contrast. It was most prominent between structures of high axonal content (internal medullary lamina, ventral nuclei) and those containing predominantly neuronal somata (pulvinar, mediodorsal thalamus, geniculate bodies). Conclusion:Semiquantitative MT saturation maps provide an enhanced intra-thalamic contrast. The borders and nuclear groups of the thalamus are reliably delineated; individual assignment of singular nuclei seems feasible.
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