It has been established that voltage-gated proton channels (VSOP/Hv1), encoded by Hvcn1, support reactive oxygen species (ROS) production in phagocytic activities of neutrophils (El Chemaly et al. ) and antibody production in B lymphocytes (Capasso et al. ). VSOP/Hv1 is a potential therapeutic target for brain ischemia, since Hvcn1 deficiency reduces microglial ROS production and protects brain from neuronal damage (Wu et al. ). In the present study, we report that VSOP/Hv1 has paradoxical suppressive role in ROS production in microglia. Extracellular ROS production was lower in neutrophils of Hvcn1 mice than WT mice as reported. In contrast, it was drastically enhanced in isolated Hvcn1 microglia as compared with cells from WT mice. Actin dynamics was altered in Hvcn1 microglia and intracellular distribution of cytosolic NADPH oxidase subunit, p67, was changed. When expression levels of oxidative stress responsive antioxidant genes were compared between WT and Hvcn1 in cerebral cortex at different ages of animals, they were slightly decreased in Hvcn1 mice at younger stage (1 day, 5 days, 3 weeks old), but drastically increased at aged stage (6 months old), suggesting that the regulation of microglial ROS production by VSOP/Hv1 is age-dependent. We also performed brain ischemic stroke experiments and found that the neuroprotective effect of VSOP/Hv1deficiency on infarct volume depended on the age of animals. Taken together, regulation of ROS production by VSOP/Hv1 is more complex than previously thought and significance of VSOP/Hv1 in microglial ROS production depends on age.

Ischemic preconditioning (IPC), a procedure consisting of transient ischemia and subsequent reperfusion, provides ischemic tolerance against prolonged ischemia in the brain. Although the blood flow changes mediated by IPC are primarily perceived by vascular endothelial cells, the role of these cells in ischemic tolerance has not been fully clarified. In this study, we found that the P2X4 receptor, which is abundantly expressed in vascular endothelial cells, is required for ischemic tolerance following middle artery occlusion (MCAO) in mice. Mechanistically, the P2X4 receptor was stimulated by fluid shear stress, which mimics reperfusion, thus promoting the increased expression of osteopontin, a neuroprotective molecule. Furthermore, we found that the intracerebroventricular administration of osteopontin was sufficient to exert a neuroprotective effect mediated by preconditioning-stimulated P2X4 receptor activation. These results demonstrate a novel mechanism whereby vascular endothelial cells are involved in ischemic tolerance.

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This study presents a computational mechanical model of coil placement in cerebral aneurysms with using realistic coil properties. The mechanical behavior of the coil is expressed by solving a variational problem including the kinetic and elastic energies of the coil and geometric constraints due to the multiple contacts. The coil is discretized as a set of beam elements obeying Timoshenko beam theory, in which these elastic properties are determined based on the actual shape and material property of the coil. Numerical examples of the coil placement are presented for four cases with different coil properties in terms of the elastic property (hard and soft) and reference configurations (helical loop and complex loop) within the realistic range. These results exhibit the effects of the coil properties on not only the transition of the coil configuration during the placement process but also the contact force of the coil against the aneurysm wall which has a fatal risk of bleeding in the operation. The proposed computational model will assist surgeons to select the appropriate coil and coil deployment protocol to achieve the sufficient treatment effectiveness with minimizing the risk of bleeding in the view of the mechanical sense.

One of the second-generation tyrosine kinase inhibitors (TKIs), nilotinib, is increasingly used for imatinib-resistant or intolerant chronic myeloid leukemia (CML). Nilotinib is considered well tolerated with few side effects including hyperglycemia, hyperbilirubinemia and elevated levels of pancreatic enzymes. However, there is growing evidence that nilotinib accelerates atherosclerosis and causes peripheral arterial occlusive disease such as stroke, transient ischemic attack (TIA) and cardiovascular diseases. Herein, we report a case of a 74-year-old male CML patient with intracranial stenosis of the internal carotid artery developed during treatment with nilotinib successfully cured by the intracranial stent, Wingspan.

BACKGROUND AND PURPOSE: Ticagrelor is a novel P2Y12 antagonist, and little is known about its efficacy and safety in the endovascular treatment of aneurysms. This study evaluated the efficacy and safety of ticagrelor versus clopidogrel for stent-assisted coiling or flow-diversion treatment in patients with unruptured cerebral aneurysms. MATERIALS AND METHODS:From November 2003 to February 2019, two hundred one patients (mean age, 57.5 years; 156 women) with 233 unruptured aneurysms underwent stent-assisted coiling or flow-diversion treatment. All patients received antiplatelet therapy of aspirin plus clopidogrel (clopidogrel group, 121 patients with 140 aneurysms) or aspirin plus ticagrelor (ticagrelor group, 80 patients with 93 aneurysms). The clinical and radiologic data in each group were retrospectively reviewed and compared.RESULTS: Two hundred thirty-six procedures were performed, including stent-assisted coiling (n ¼ 101) and flow diversion (n ¼ 135). At 90 days, the primary outcome-a composite of any stroke and death-occurred in 9.9% of the clopidogrel group and 8.6% of the ticagrelor group (P ¼ .822). Ischemic stroke occurred in 10 (7.0%) of the clopidogrel group and 7 (7.5%) of the ticagrelor group (P . .999). Disabling stroke occurred in 4 (2.8%) in the clopidogrel group and in 4 (4.3%) in the ticagrelor group (P ¼ .716). Ninety-day death occurred in 3 (2.1%) in the clopidogrel group and 1 (1.1%) in the ticagrelor group (P . .999). Any bleeding at 90 days occurred in 13 (9.2%) in the clopidogrel group and 6 (6.5%) in the ticagrelor group (P ¼ .479).

One of the most crucial yet challenging issues for glioma patient care is visualizing non-contrast-enhancing tumor regions. In this study, to test the hypothesis that quantitative magnetic resonance relaxometry reflects glioma tumor load within tissue and that it can be an imaging surrogate for visualizing non-contrast-enhancing tumors, we investigated the correlation between T1- and T2-weighted relaxation times, apparent diffusion coefficient (ADC) on magnetic resonance imaging, and 11C-methionine (MET) on positron emission tomography (PET). Moreover, we compared the T1- and T2-relaxation times and ADC with tumor cell density (TCD) findings obtained via stereotactic image-guided tissue sampling. Regions that presented a T1-relaxation time of >1850 ms but <3200 ms or a T2-relaxation time of >115 ms but <225 ms under 3 T indicated a high MET uptake. In addition, the stereotactic tissue sampling findings confirmed that the T1-relaxation time of 1850–3200 ms significantly indicated a higher TCD (p = 0.04). However, ADC was unable to show a significant correlation with MET uptake or with TCD. Finally, synthetically synthesized tumor load images from the T1- and T2-relaxation maps were able to visualize MET uptake presented on PET.