Tomohiko Ozaki

The P2X4 receptor is required for neuroprotection via ischemic preconditioning

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.

Brachial–Ankle Pulse Wave Velocity as a Predictor of Silent Cerebral Embolism after Carotid Artery Stenting

BACKGROUND In neuroendovascular therapy, the effect of arterial stiffness on postprocedural cerebral thromboembolism is unknown. In this observational study, we examined the relationship between cerebral thromboembolism after carotid artery stenting and arterial stiffness. METHODS From April 2015 to February 2017, we enrolled consecutive patients undergoing scheduled carotid artery stenting in our institution. In all patients, preprocedural brachial-ankle pulse wave velocity was used to assess arterial stiffness, whereas the number of new cerebral ischemic lesions on diffusion-weighted magnetic resonance imaging was assessed after treatment. We also analyzed patient data and details of procedures in patients with carotid artery stenting. RESULTS Twenty-one patients completed the study. The mean brachial-ankle pulse wave velocity was 1879 cm/s. There was no association of cerebral thromboembolisms with age, unstable plaque, protection device, or type of stent. However, the brachial-ankle pulse wave velocity was an independent predictor of cerebral thromboembolisms (P = .0017). CONCLUSIONS Brachial-ankle pulse wave velocity is predictive of silent cerebral embolisms on diffusion-weighted magnetic resonance imaging after carotid artery stenting.

Unconventional role of voltage-gated proton channels (VSOP/Hv1) in regulation of microglial ROS production

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.

Endovascular and Surgical Treatment of Spinal Dural Arteriovenous Fistulas: Assessment of Post-treatment Clinical Outcome

Spinal dural arteriovenous fistulas (DAVFs) are the most commonly encountered vascular malformation of the spinal cord and a treatable cause of progressive para- or tetraplegia. It is an elusive pathology that tends to be under-diagnosed, due to lack of awareness among clinicians, and affects males more commonly than females, typically between the fifth and eighth decades. Early diagnosis and treatment may significantly improve outcome and prevent permanent disability and even mortality. The purpose of our retrospective, single-center study was to determine the long-term clinical and radiographic outcome of patients who have received endovascular or surgical treatment of a spinal DAVF. In particular, during a 6-year period (2009–2014) 14 patients with a spinal DAVF were treated at our department either surgically (n = 4) or endovascularly (n = 10) with detachable coils and/or glue. There was no recurrence in the follow-up period (mean: 36 months, range 3–60 months) after complete occlusion with the endovascular treatment (n = 9; 90%), while only one patient (10%) had residual flow both post-treatment and at 3-month follow-up. All four surgically treated patients (100%) had no signs of residual DAVF on follow-up magnetic resonance angiography (MRA) and/or angiography (mean follow-up period of 9 months). Since improvement or stabilization of symptoms may be seen even in patients with delayed diagnosis and substantial neurological deficits, either endovascular or surgical treatment is always justified.

Transarterial Sinus Embolization for a Dural Arteriovenous Fistula in a Sinus of the Lesser Sphenoid Wing: A Case Report

Dural arteriovenous fistula (DAVF) in a sinus of the lesser sphenoid wing (SLSW) is rarely reported. Here, we report a case of an isolated SLSW DAVF treated by coils placed into the sinus through the feeding artery. A 68-year-old man was admitted to our hospital with headache. Magnetic resonance images and an angiogram showed a varix in the right middle cranial fossa. A DAVF, consisting of three main feeders and the isolated SLSW, was diagnosed based on the angiogram findings. Retrograde leptomeningeal venous drainage to the deep middle cerebral vein was observed. Given the remarkable extent of cortical venous ectasia together with the presence of headache and right abducens nerve paralysis, endovascular treatment was initiated. A transvenous approach through the right inferior petrosal sinus was not feasible because of difficulty associated with inserting the microcatheter into the SLSW. Thus, we tried a transarterial approach and were able to advance the microcatheter beyond the fistula into the isolated SLSW, through the artery of the foramen rotundum. The isolated sinus and feeding arteries were embolized with coils. The postoperative angiogram showed the total occlusion of the SLSW DAVF. This case demonstrates the feasibility of transarterial sinus packing for an isolated SLSW DAVF.

Intracranial stenting for nilotinib treatment-associated cerebrovascular stenosis in chronic myeloid leukemia

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.

Direct aspiration first pass technique for a middle cerebral artery occlusion with a hidden aneurysm.

Hidden aneurysms within occluded vessels present a challenge for interventionists because vessel perforation can lead to life-threatening complications. We present a case of middle cerebral artery ischemic stroke, refractory to thrombolysis. A direct aspiration first pass technique (ADAPT) was employed for revascularization. Following thrombectomy, an aneurysm of the occluded vessel was revealed. Despite this, the patient recovered without hemorrhagic complication. ADAPT permits the minimal insertion of endovascular devices and might be a safe procedure when hidden aneurysms are suspected.

Coil and Single Stent Placement for Ruptured Dissecting Aneurysm of Middle Cerebral Artery: a case report.

BACKGROUND Ruptured dissecting aneurysms located at the middle cerebral artery (MCA) are rare, and their standard treatment has not been defined. Furthermore, lenticulostriate artery involvement in the dissecting segment makes treatment extremely difficult, and no previous reports have described successful treatment for such conditions. CASE DESCRIPTION We herein report the case of a 74-year-old woman who presented with sudden severe headache from subarachnoid hemorrhage due to dissection in the proximal M1 segment of left MCA involving lenticulostriate arteries. Digital subtraction angiography on day 6 showed that the dissecting aneurysm had enlarged despite strict blood pressure control. On day 8, the patient was treated successfully with a self-expanding closed cell stent and coil embolization, preserving blood flow in the lenticulostriate arteries as well as the MCA. CONCLUSIONS Follow-up digital subtraction angiography performed 5 weeks after endovascular therapy showed healing of the dissecting lesion, and the patient was discharged neurologically intact.

Enlargement of papillary glioneuronal tumor in an adult after a follow-up period of 10 years: a case report

Abstract Papillary glioneuronal tumor (PGNT) is a rare brain tumor grouped under mixed glioneuronal tumors according to the World Health Organization Classification of the Central Nervous System. The natural history of this pathology is not yet well documented. We report a case of PGNT that increased in size after a follow-up period of 10 years. An enlarged cyst wall and nodule showed a low intensity signal on T2*-weighted, suggesting hemorrhage during the clinical course. Characteristic pathological findings along with absence of BRAFV600E mutation identified the tumor as PGNT. The tumor characteristics of PGNT are discussed based on the presented case, with reference to the existing literature.

Voxel-Based Lesion Mapping of Cryptogenic Stroke in Patients with Advanced Cancer: A Detailed Magnetic Resonance Imaging Analysis of Distribution Pattern

BACKGROUND Ischemic stroke is one form of cancer-associated thrombosis that can greatly worsen a patients performance status. The present investigation aimed to elucidate the characteristic distribution pattern(s) of cryptogenic stroke lesions using a voxel-based lesion-mapping technique and examine the differences in clinical manifestations between cryptogenic and conventional strokes in patients with advanced cancer. METHODS Data from 43 patients with advanced cancer who developed acute ischemic stroke were retrospectively collected. Stroke etiology was grouped into either cryptogenic or conventional stroke etiology according to the ASCO stroke score. Clinical data were reviewed, and voxel-based lesion mapping using diffusion-weighted imaging (DWI) was performed to visualize the cross-patient spatial distribution of the lesions. RESULTS Of the 43 patients, 25 were classified as having cryptogenic stroke etiology and 18 were classified as having conventional stroke etiology. Median survival time of patients from stroke onset was 96 days for cryptogenic stroke etiology and 570 days for conventional stroke etiology (P = .01). D-dimer of patients was significantly higher in cryptogenic stoke etiology than in conventional stroke etiology (P = .006). Voxel-based lesion mapping showed that DWI hyperintense lesions accumulated at cortical and internal watershed areas of the cerebrum and at the vascular border zone of the superior cerebellar and posterior inferior cerebellar arteries at the cerebellum. CONCLUSIONS Voxel-based lesion mapping for cryptogenic stroke in patients with advanced cancer showed that lesions accumulated at vascular border zones within the brain both at the cerebrum and at the cerebellum, but not at perforating arterial territories.