Ischemic stroke prompts a strong inflammatory response, which is associated with exacerbated outcomes. In this study, we investigated mechanistic regulators of neutrophil extracellular trap (NET) formation in stroke and whether they contribute to stroke outcomes. NET-forming neutrophils were found throughout brain tissue of ischemic stroke patients, and elevated plasma NET biomarkers correlated with worse stroke outcomes. Additionally, we observed increased plasma and platelet surface–expressed high-mobility group box 1 (HMGB1) in stroke patients. Mechanistically, platelets were identified as the critical source of HMGB1 that caused NETs in the acute phase of stroke. Depletion of platelets or platelet-specific knockout of HMGB1 significantly reduced plasma HMGB1 and NET levels after stroke, and greatly improved stroke outcomes. We subsequently investigated the therapeutic potential of neonatal NET-inhibitory factor (nNIF) in stroke. Mice treated with nNIF had smaller brain infarcts, improved long-term neurological and motor function, and enhanced survival after stroke. nNIF specifically blocked NET formation without affecting neutrophil recruitment after stroke. Importantly, nNIF also improved stroke outcomes in diabetic and aged mice and was still effective when given 1 hour after stroke onset. These results support a pathological role for NETs in ischemic stroke and warrant further investigation of nNIF for stroke therapy.
Hydraulic conductivity (K) and specific storage (S(s)) are required parameters when designing transient groundwater flow models. The purpose of this study was to evaluate the ability of commonly used hydrogeologic characterization approaches to accurately delineate the distribution of hydraulic properties in a highly heterogeneous glaciofluvial deposit. The metric used to compare the various approaches was the prediction of drawdown responses from three separate pumping tests. The study was conducted at a field site, where a 15 m × 15 m area was instrumented with four 18-m deep Continuous Multichannel Tubing (CMT) wells. Each CMT well contained seven 17 cm × 1.9 cm monitoring ports equally spaced every 2 m down each CMT system. An 18-m deep pumping well with eight separate 1-m long screens spaced every 2 m was also placed in the center of the square pattern. In each of these boreholes, cores were collected and characterized using the Unified Soil Classification System, grain size analysis, and permeameter tests. To date, 471 K estimates have been obtained through permeameter analyses and 270 K estimates from empirical relationships. Geostatistical analysis of the small-scale K data yielded strongly heterogeneous K fields in three-dimensions. Additional K estimates were obtained through slug tests in 28 ports of the four CMT wells. Several pumping tests were conducted using the multiscreen and CMT wells to obtain larger scale estimates of both K and S(s). The various K and S(s) estimates were then quantitatively evaluated by simulating transient drawdown data from three pumping tests using a 3D forward numerical model constructed using HydroGeoSphere (Therrien et al. 2005). Results showed that, while drawdown predictions generally improved as more complexity was introduced into the model, the ability to make accurate drawdown predictions at all CMT ports was inconsistent.
BACKGROUND Endovascular surgery is the first-line treatment for indirect cavernous carotid fistulae (CCFs). This study compares multiple treatment techniques. OBJECTIVE To compare endovascular techniques for indirect CCF treatment. METHODS Retrospective analysis was performed of prospectively maintained records at 4 centers, identifying patients undergoing indirect CCF embolization. Demographics, symptoms, and lesion characteristics were recorded. Medical records were reviewed for changes in symptoms, delayed complications, and angiographically proven recurrence. Univariate and multivariate analyses were performed to identify impacts of the above characteristics on outcomes. RESULTS Sufficient records were available for 267 patients treated between January 1987 and December 2016. Obliteration was achieved in 86.5% patients, occurring in 86.9% of exclusively transvenous treatments and 79.5% of other treatments. Obliteration rates were highest following transvenous embolization using coils compared to all other materials (likelihood ratio [LR] 5.0, P = .024). Complications were less common with coil embolization compared to other materials (LR 0.070, P < .001). Embolization with liquid embolics resulted in higher complication rates (LR 10.2, P = .002), although risk was reduced when used in conjunction with coils. Angiographically confirmed recurrence was more common following embolization with polyvinyl alcohol (LR 9.9, P = .004) and when multiple embolic agents were used (LR 6.6, P = .018). Delayed development of symptoms following embolization was less common following embolization with coils (LR 0.20, P = .030) and more common following embolization with liquids (LR 6.5, P = .014). CONCLUSION To treat indirect CCFs, transvenous coil embolization is the safest and most effective technique. Liquid embolics are less effective and have more complications and should be carefully considered only in extenuating circumstances.
Accurate and timely diagnosis of intracranial vasculopathies is important due to significant risk of morbidity with delayed and/or incorrect diagnosis both from the disease process as well as inappropriate therapies. Conventional vascular imaging techniques for analysis of intracranial vascular disease provide limited information since they only identify changes to the vessel lumen. New advanced MR intracranial vessel wall imaging (IVW) techniques can allow direct characterisation of the vessel wall. These techniques can advance diagnostic accuracy and may potentially improve patient outcomes by better guided treatment decisions in comparison to previously available invasive and noninvasive techniques. While neuroradiological expertise is invaluable in accurate examination interpretation, clinician familiarity with the application and findings of the various vasculopathies on IVW can help guide diagnostic and therapeutic decision-making. This review article provides a brief overview of the technical aspects of IVW and discusses the IVW findings of various intracranial vasculopathies, differentiating characteristics and indications for when this technique can be beneficial in patient management.
Background and Purpose Although studies have evaluated the differential imaging of moyamoya disease and atherosclerosis, none have investigated the added value of vessel-wall MRI. The current study evaluates the added diagnostic value of vessel-wall MRI in differentiating moyamoya disease (MMD), atherosclerotic-moyamoya syndrome (A-MMS) and vasculitic-moyamoya syndrome (V-MMS) with a multi-contrast protocol. Methods We retrospectively reviewed the carotid artery territories of patients with clinically defined vasculopathies (MMD, atherosclerosis, vasculitis) and steno-occlusive intracranial carotid disease. Two neuroradiologists, blinded to clinical data reviewed the luminal imaging of each carotid, evaluating collateral extent and making a presumed diagnosis with diagnostic confidence. After three weeks, the two readers reviewed the luminal imaging+vessel-wall MRI for presence, pattern and intensity of post-contrast enhancement, T2 signal characteristics, pattern of involvement, presumed diagnosis and confidence. Results Ten A-MMS, three V-MMS and eight MMD cases with 38 affected carotid segments were included. There was significant improvement in diagnostic accuracy with luminal imaging+vessel-wall MRI as compared to luminal imaging (87% vs. 32%, p<.001). The most common vessel-wall MRI findings for MMD were non-enhancing, non-remodeling lesions without T2 heterogeneity; for A-MMS eccentric, remodeling, and T2 heterogeneous lesions with mild/moderate and homogeneous/heterogeneous enhancement; and for V-MMS concentric lesions with homogeneous, moderate enhancement. Inter-reader agreement was moderate to substantial for all vessel-wall MRI characteristics (κ=0.46-0.86) and fair for collateral grading (κ=0.35). There was 11% inter-reader agreement for diagnosis on luminal imaging as compared to 82% for luminal imaging+vessel-wall MRI (p<.001). Conclusion Vessel-wall MRI can significantly improve the differentiation of moyamoya vasculopathies when combined with traditional imaging techniques.
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