1,720,978 research outputs found
MICROGLIAL CELL ACTIVATION BY LIPOPOLYSACCHARIDE DOES NOT INDUCE NEUROTOXICITY IN ORGANOTYPIC HIPPOCAMPAL SLICE CULTURES
No full textMICROGLIAL CELL ACTIVATION BY LIPOPOLYSACCHARIDE DOES NOT INDUCE NEUROTOXICITY IN ORGANOTYPIC HIPPOCAMPAL SLICE CULTURES
No full textFREE RADICAL DEPENDENT NEUROVASCULAR DE-COUPLING IN AN IN VITRO MODEL OF STATUS EPILEPTICUS
No full text
FREE RADICAL DEPENDENT NEUROVASCULAR DE-COUPLING IN AN IN VITRO MODEL OF STATUS EPILEPTICUS
No full textTLR4-activated microglia require IFN-gamma to induce severe neuronal dysfunction and death in situ
No full textMicroglia (tissue-resident macrophages) represent the main cell type of the innate immune system in the CNS; however, the mechanisms that control the activation of microglia are widely unknown. We systematically explored microglial activation and functional microglia-neuron interactions in organotypic hippocampal slice cultures, i.e., postnatal cortical tissue that lacks adaptive immunity. We applied electrophysiological recordings of local field potential and extracellular K+ concentration, immunohistochemistry, design-based stereology, morphometry, Sholl analysis, and biochemical analyses. We show that chronic activation with either bacterial lipopolysaccharide through Toll-like receptor 4 (TLR4) or leukocyte cytokine IFN-gamma induces reactive phenotypes in microglia associated with morphological changes, population expansion, CD11b and CD68 up-regulation, and proinflammatory cytokine (IL-1 beta, TNF-alpha, IL-6) and nitric oxide (NO) release. Notably, these reactive phenotypes only moderately alter intrinsic neuronal excitability and gamma oscillations (30-100 Hz), which emerge from precise synaptic communication of glutamatergic pyramidal cells and fast-spiking, parvalbumin-positive GABAergic interneurons, in local hippocampal networks. Short-term synaptic plasticity and extracellular potassium homeostasis during neural excitation, also reflecting astrocyte function, are unaffected. In contrast, the coactivation of TLR4 and IFN-gamma receptors results in neuronal dysfunction and death, caused mainly by enhanced microglial inducible nitric oxide synthase (iNOS) expression and NO release, because iNOS inhibition is neuroprotective. Thus, activation of TLR4 in microglia in situ requires concomitant IFN-gamma receptor signaling from peripheral immune cells, such as T helper type 1 and natural killer cells, to unleash neurotoxicity and inflammation-induced neurodegeneration. Our findings provide crucial mechanistic insight into the complex process of microglia activation, with relevance to several neurologic and psychiatric disorders.German Research Foundation [SFB/TRR43, FOR1336
Restoration of Bi-Contrast MRI Data for Intensity Uniformity with Bayesian Coring of Co-Occurrence Statistics
No full textThe reconstruction of MRI data assumes a uniform radio-frequency field. However, in practice, the radio-frequency field is inhomogeneous and leads to anatomically inconsequential intensity non-uniformities across an image. An anatomic region can be imaged with multiple contrasts reconstructed independently and be suffering from different non-uniformities. These artifacts can complicate the further automated analysis of the images. A method is presented for the joint intensity uniformity restoration of two such images. The effect of the intensity distortion on the auto-co-occurrence statistics of each image as well as on the joint-co-occurrence statistics of the two images is modeled and used for their non-stationary restoration followed by their back-projection to the images. Several constraints that ensure a stable restoration are also imposed. Moreover, the method considers the inevitable differences between the signal regions of the two images. The method has been evaluated extensively with BrainWeb phantom brain data as well as with brain anatomic data from the Human Connectome Project (HCP) and with data of Parkinson’s disease patients. The performance of the proposed method has been compared with that of the N4ITK tool. The proposed method increases tissues contrast at least 4 . 62 times more than the N4ITK tool for the BrainWeb images. The dynamic range with the N4ITK method for the same images is increased by up to +29.77%, whereas, for the proposed method, it has a corresponding limited decrease of - 1 . 15 % , as expected. The validation has demonstrated the accuracy and stability of the proposed method and hence its ability to reduce the requirements for additional calibration scans
Evaluation of an optimized metal artifact reduction algorithm for flat-detector angiography compared to DSA imaging in follow-up after neurovascular procedures
No full textShifts in excitatory/inhibitory balance by juvenile stress: A role for neuron–astrocyte interaction in the dentate gyrus
No full textChildhood trauma is a well-described risk factor for the development of stress-related psychopathology such as posttraumatic stress disorder or depression later in life. Childhood adversity can be modeled in rodents by juvenile stress (JS) protocols, resulting in impaired coping with stressful challenges in adulthood. In the current study, we investigated the long-lasting impact of JS on the expression of molecular factors for glutamate and gamma-aminobutyric acid (GABA) uptake and turnover in sublayers of the dentate gyrus (DG) using laser microdissection and quantitative real-time polymerase chain reaction. We observed reduced mRNA expression levels after JS for factors mediating astrocytic glutamate and GABA uptake and degradation. These alterations were prominently observed in the dorsal but not ventral DG granule cell layer, indicating a lasting change in astrocytic GABA and glutamate metabolism that may affect dorsal DG network activity. Indeed, we observed increased inhibition and a lack of facilitation in response to paired-pulse stimulation at short interstimulus intervals in the dorsal DG after JS, while no alterations were evident in basal synaptic transmission or forms of long-term plasticity. The shift in paired-pulse response was mimicked by pharmacologically blocking the astrocytic GABA transporter GAT-3 in naive animals. Accordingly, reduced expression levels of GAT-3 were confirmed at the protein level in the dorsal granule cell layer of rats stressed in juvenility. Together, these data demonstrate a lasting shift in the excitatory/inhibitory balance of dorsal DG network activity by JS that appears to be mediated by decreased GABA uptake into astrocytes
Computed tomography perfusion-based selection of endovascularly treated acute ischaemic stroke patients – Are there lessons to be learned from the pre-evidence era?
No full textIntroduction Some of the latest groundbreaking trials suggest that noncontrast cranial computed tomography and computed tomography-angiography are sufficient tools for patient selection within six hours of symptom onset. Before endovascular stroke therapy became the standard of care, patient selection was one of the most useful tools to avoid futile reperfusions. We report the outcomes of endovascularly treated stroke patients selected with a perfusion-based paradigm and discuss the implications in the current era of endovascular treatment. Material and methods After an interdisciplinary meeting in September 2012 we agreed to select thrombectomy candidates primarily based on computed tomography perfusion with a cerebral blood volume Alberta Stroke Program Early Computed Tomography Scale (CBV-ASPECTS) of <7 being a strong indicator of futile reperfusion. In this study, we retrospectively screened all patients with an M1 thrombosis in our neurointerventional database between September 2012 and December 2014. Results In 39 patients with a mean age of 69 years and a median admission National Institute of Health Stroke Scale of 17 the successful reperfusion rate was 74% and the favourable outcome rate at 90 days was 56%. Compared to previously published data from our database 2007–2011, we found that a two-point increase in median CBV-ASPECTS was associated with a significant increase in favourable outcomes. Conclusion Computed tomography perfusion imaging as an additional selection criterion significantly increased the rate of favourable clinical outcome in patients treated with mechanical thrombectomy. Although computed tomography perfusion has lost impact within the six-hour period, we still use it in cases beyond six hours as a means to broaden the therapeutic window. </jats:sec
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