Tomoya Kamide

RAGE mediates vascular injury and inflammation after global cerebral ischemia

The receptor for advanced glycation end products (RAGE) is a multi-ligand receptor involved in a diverse range of pathological conditions. To analyze the roles of RAGE and its decoy receptor, endogenous secretory RAGE (esRAGE), in the global cerebral ischemia, three different mouse cohorts, wild-type, RAGE⁻/⁻, and esRAGE transgenic (Tg) mice were subjected to bilateral common carotid artery occlusion (BCCAO). RT-PCR and immunohistochemical analysis revealed that expression of RAGE was induced in the vascular cells at 12 h, and then in the neurons and glia from 3 to 7 days in the hippocampus after BCCAO. The numbers of surviving neurons in the hippocampal CA1 region were significantly higher in RAGE⁻/⁻ and esRAGE Tg mice than those in wild-type mice in the periods between 24 h and 7 days after BCCAO. Lower levels of 3-nitrotyrosine (3-NT) and higher levels of endothelial nitric oxide synthase (eNOS), together with enlarged vascular areas were observed in RAGE⁻/⁻ and esRAGE Tg mice at 12 h after BCCAO. In the later periods, expressions of glia-derived inflammatory mediators TNFα and inducible nitric oxide synthase (iNOS) were reduced in RAGE⁻/⁻ and esRAGE Tg mice. These results suggest that RAGE may contribute to delayed neuronal death after global cerebral ischemia by enhancing vascular injury and deleterious glia-mediated inflammation.

Deletion of Atf6α impairs astroglial activation and enhances neuronal death following brain ischemia in mice.

To dissect the role of endoplasmic reticulum (ER) stress and unfolded protein response in brain ischemia, we investigated the relevance of activating transcription factor 6α (ATF6α), a master transcriptional factor in the unfolded protein response, after permanent middle cerebral artery occlusion (MCAO) in mice. Enhanced expression of glucose‐regulated protein78, a downstream molecular chaperone of ATF6α, was observed in both neurons and glia in the peri‐infarct region of wild‐type mice after MCAO. Analysis using wild‐type and Atf6α−/− mice revealed a larger infarct volume and increased cell death in the peri‐ischemic region of Atf6α−/− mice 5 days after MCAO. These phenotypes in Atf6α−/− mice were associated with reduced levels of astroglial activation/glial scar formation, and a spread of tissue damage into the non‐infarct area. Further analysis in mice and cultured astrocytes revealed that signal transducer and activator of transcription 3 (STAT3)‐glial fibrillary acidic protein signaling were diminished in Atf6α−/− astrocytes. A chemical chaperone, 4‐phenylbutyrate, restored STAT3‐glial fibrillary acidic protein signaling, while ER stressors, such as tunicamycin and thapsigargin, almost completely abolished signaling in cultured astrocytes. Furthermore, ER stress‐induced deactivation of STAT3 was mediated, at least in part, by the ER stress‐responsive tyrosine phosphatase, TC‐PTP/PTPN2. These results suggest that ER stress plays critical roles in determining the level of astroglial activation and neuronal survival after brain ischemia.

Arterial spin-labeling magnetic resonance imaging for diagnosis of early seizure after stroke

BACKGROUND AND PURPOSE Arterial spin labeling (ASL) is a non-invasive modality of magnetic resonance imaging (MRI) used to evaluate cerebral perfusion without a contrast agent. The usefulness of ASL for diagnosis in the acute phase of late seizure after stroke was evaluated. METHODS Twelve consecutive patients diagnosed with late seizure after stroke were enrolled in this study. MRI including ASL was performed for each patient at the time of the emergency department visit. Eight of the patients underwent electroencephalography (EEG). RESULTS All patients showed hyperperfusion around the stroke lesion on ASL. Only 6 patients showed high signal intensity along the cerebral cortex around the stroke lesion on diffusion-weighted imaging. The patients who underwent EEG showed slow activity, but paroxysmal discharges such as spikes or sharp waves were not observed. CONCLUSIONS ASL was able to reveal hyperperfusion and was of great diagnostic value in the peri-ictal phase of late seizure after stroke.

Radiation-induced cerebellar high-grade glioma accompanied by meningioma and cavernoma 29 years after the treatment of medulloblastoma: a case report

Here, we report the case of a patient with cerebellar high-grade glioma that developed after the patient underwent treatment for medulloblastoma. A 34-year-old man visited our hospital with complaints of dizziness and truncal ataxia. Magnetic resonance image showed a cerebellar tumor with multiple cavernomas and two lesions that were suspected to be meningiomas. The cerebellar tumor was surgically removed. According to pathological examination, the tumor was a high-grade glioma that was positive for methylated O-6-methylguanine-DNA methyltransferase promoter. In the past, he had received radiotherapy at the age of 5, after which he was operated for desmoplastic medulloblastoma in his right cerebellar hemisphere. Seven years after the initial therapy, cavernoma-induced intracerebral hemorrhage of the right temporal lobe was noted. To our knowledge, this is the first case of radiation-induced double intracranial tumors accompanied by symptomatic cavernoma.

Skull osteohypertrophy as a complication of bone wax

A 51-year-old woman with bone wax-induced osteohypertrophy presented with exophthalmos 9 years after a craniotomy for a right internal carotid bifurcation aneurysm. CT scans revealed thickening of the frontotemporal bone flap and surrounding bone, thickening of the upper and lateral orbital walls, and a limited intraorbital cavity. Intraoperative findings revealed residual bone wax under the bone flap, grayish-white discoloration of the flap, and degeneration of the temporal muscle. Pathological examination revealed granulation and osteogenesis due to a foreign body. To our knowledge, this is the first report of bone wax-induced hyperostosis leading to exophthalmos.

Intraparenchymal pneumocephalus caused by ethmoid sinus osteoma

We report a 57-year-old man with intraparenchymal pneumocephalus caused by ethmoid sinus osteoma. He had a history of severe allergic rhinitis, which caused him to frequently blow his nose, and he was referred to our hospital with headache and mild left hemiparesis. CT scans revealed a large volume of intraparenchymal air entrapped in the right frontal lobe related to an osteoma in the ethmoid sinus. The osteoma eroded the upper wall of the sinus and extended into the anterior cranial fossa. At operation, we observed that the osteoma had protruded intracranially through the skull base, disrupted the dura and extended into the frontal lobe. To our knowledge, this is the first report of a patient with intraparenchymal pneumocephalus caused by an ethmoid sinus osteoma.

Epithelioid glioblastoma changed to typical glioblastoma: the methylation status of MGMT promoter and 5-ALA fluorescence

A 55-year-old man was admitted to our hospital complaining of left hemiparesis. Magnetic resonance imaging (MRI) showed a smooth ring-like enhanced cystic tumor in the right parietal lobe. He underwent gross total resection of the tumor under neuronavigation and 5-aminolevulinic acid (5-ALA) fluorescence guiding method. Histopathological examination of the tumor showed small cells formed epithelioid solid nests with some focus of duct-like structure. On the basis of the MRI and operative and histological findings, this tumor was diagnosed as a metastatic poorly differentiated carcinoma, although the primary cancer could not be detected by metastatic work-ups. Afterward, this tumor recurred repeatedly. Histopathological examination of specimen from the fourth surgery indicated that the tumor was a glioblastoma (GBM). In the review of the histology and immunohistochemistry of the first tumor, atypical fibrillary cells were seen between solid nests and positive for glial fibrillary acidic protein, therefore the tumor was retrospectively diagnosed as epithelioid GBM. We assessed whether the changes in histopathology were accompanied by changes in the methylation status of O6-methylguanine methyltransferase (MGMT) promoter and the status of 5-ALA fluorescence. The methylation status of the MGMT promoter was found to have changed from methylated to unmethylated and 5-ALA fluorescence became positive along with the histological change.

Cavernous Sinus Dural Arteriovenous Fistula Patients Presenting With Headache as an Initial Symptom

Cavernous sinus (CS) dural arteriovenous fistula (dAVF) patients presenting with only headache as an initial symptom are not common. Patients with CS-dAVF commonly present with symptoms related to their eyes. In all three patients, headache was the initial symptom. Other symptoms related to the eyes developed 1 - 7 months after headache. In one patient, headache was controlled by sumatriptan succinate, but not diclofenac sodium or loxoprofen sodium. In another patient, headache was controlled by loxoprofen sodium. In the third patient, headache was improved by stellate ganglion block. In all patients, magnetic resonance angiography (MRA) in the early stage of the clinical course showed abnormal blood flow in the CS. However, reflux to the superior ophthalmic vein (SOV) was not detected. As treatment, transarterial and transvenous embolizations were necessary for one patient, and transvenous embolization was performed for another patient with significant blood flow to the SOV and cortical veins. On the other hand, manual compression of the bilateral carotid arteries at the neck resulted in disappearance of the fistula in the third patient. In all patients, the symptoms improved after the disappearance of blood reflux to the CS. The refluxed blood to the CS might cause elevation of the CS pressure and stimulate the trigeminal nerve in the dural membrane, resulting in headache before developing reflux in an anterior direction. CS-dAVF could induce both migraine and common headache. In cases with blood reflux to the CS on magnetic resonance imaging and/or MRA even without eye symptoms, a differential diagnosis of CS-dAVF should be taken into consideration.

Delayed asymptomatic coil migrations toward different arteries after aneurysmal embolization: case report.

Delayed coil migration after endovascular treatment with detachable coils, particularly several months after treatment, is extremely rare. In this report, the authors describe a 77-year-old female in whom delayed coil migration to the anterior cerebral artery and posterior communicating artery (PCoA) developed 3 months after an uncomplicated aneurysm embolization. The patient was successfully retreated with a closed-cell stent. Computational fluid dynamics (CFD) revealed high wall shear stress (WSS) and multiple vortices in the residual cavity of the initially treated aneurysm. CFD could be useful to detect and predict this complication, and a stent-assisted technique could be an important treatment option.

Pseudoaneurysm formation caused by the withdrawal of a Trevo ProVue stent at a tortuous cerebral vessel: a case report.

This is the first report on the mechanism of pseudoaneurysm formation after withdrawal of a stent retriever. A 79-year-old woman developed cardiogenic embolization of the distal middle cerebral artery (M2). The deployed stent retriever bent because of vessel tortuosity. After withdrawal of the stent with strong resistance, complete revascularization was achieved, but an extravasation was detected at the site. Eight hours after disappearance of the extravasation, re-bleeding occurred with aneurysm-like pooling of contrast media. Direct surgical observation confirmed a pseudoaneurysm formation. The pseudoaneurysm was likely formed by avulsion of a fine vessel during withdrawal of the stent retriever at a tortuous vessel.