Myelination- and migration-associated genes are downregulated after phagocytosis in cultured oligodendrocyte precursor cells.

In the central nervous system, microglia are responsible for removing infectious agents, damaged/dead cells, and amyloid plaques by phagocytosis. Other cell types, such as astrocytes, are also recently recognized to show phagocytotic activity under some conditions. Oligodendrocyte precursor cells (OPCs), which belong to the same glial cell family as microglia and astrocytes, may have similar functions. However, it remains largely unknown whether OPCs exhibit phagocytic activity against foreign materials like microglia. To answer this question, we examined the phagocytosis activity of OPCs using primary rat OPC cultures. Since innate phagocytosis activity could trigger cell death pathways, we also investigated whether participating in phagocytosis activity may lead to OPC cell death. Our data shows that cultured OPCs phagocytosed myelin-debris-rich lysates prepared from rat corpus callosum, without progressing to cell death. In contrast to OPCs, mature oligodendrocytes did not show phagocytotic activity against the bait. OPCs also exhibited phagocytosis towards lysates of rat brain cortex and cell membrane debris from cultured astrocytes, but the percentage of OPCs that phagocytosed beta-amyloid was much lower than the myelin debris. We then conducted RNA-seq experiments to examine the transcriptome profile of OPC cultures and found that myelination- and migration-associated genes were downregulated 24 h after phagocytosis. On the other hand, there were a few upregulated genes in OPCs 24 h after phagocytosis. These data confirm that OPCs play a role in debris removal and suggest that OPCs may remain in a quiescent state after phagocytosis.

Neuronal dysfunction and hemodynamic disturbance due to venous congestion in dural arteriovenous fistula revealed by 123I-iomazenil SPECT.

OBJECTIVE: Retrograde leptomeningeal venous drainage (RLVD) of a dural arteriovenous fistula (dAVF) is associated with neurological morbidity and unfavorable outcomes. However, the direct damage to cortical neurons by dAVF with RLVD has not been elucidated. 123I-iomazenil (123I-IMZ) SPECT can reveal cerebral blood flow and cortical neuronal damage in early and late images, respectively. This study aimed to assess the cerebral venous congestive encephalopathy caused by dAVF using 123I-IMZ SPECT. METHODS: Based on the pre- and posttreatment MRI findings, patients were divided into three groups: a normal group, an edema group, and an infarction group. Radioactive counts in the early and late images of 123I-IMZ SPECT were investigated using the affected-to-contralateral side asymmetry ratio (ACR). RESULTS: None of the patients in the normal group showed any symptoms related to venous congestion. In contrast, all the patients in the edema and infarction groups developed neurological symptoms. The ACR in early images in the edema group was significantly lower than that in the normal group and significantly higher than that in the infarction group. The ACR in the late images of the infarction group was significantly lower than those of the normal and edema groups. After treatment, the neurological signs disappeared in the edema group, but only partial improvement was observed in the infarction group. The ACR in early images significantly improved after treatment in the edema group, but the ACR in late images did not change in any groups. CONCLUSIONS: 123I-IMZ SPECT is useful for evaluating hemodynamic disturbances and neuronal damage in dAVFs. The reduction in early images was correlated with the severity of venous congestive encephalopathy, and the significant reduction in late images is a reliable indicator of irreversible venous infarction caused by RLVD.

Blood Blister-Like Aneurysms at the Junction of the Internal Carotid and Posterior Communicating Artery: Characteristics and Treatment Strategies.

BACKGROUND: Blood blister-like aneurysms (BBAs) usually arise from the anterior walls of the internal carotid artery, and such lesions at the junction of the internal carotid artery and posterior communicating artery (PCoA) have not been reported to date. Here, we report our experiences of BBAs at PCoA. We studied their clinical and angiographical characteristics including the internal carotid-PCoA angle, an indicator of hemodynamic stress at the bifurcation. METHODS: Three patients with BBAs located at the origin of PCoA were studied. Wrap-clipping was adopted as the first-line therapy, but direct clipping was conducted when difficult. RESULTS: All patients were elderly females (mean age 81.3 years), and BBAs were small in size (mean maximum diameter 1.5 mm), which arose at the origins of wide-angled fetal-type PCoAs (mean internal carotid-PCoA angle 37.8 degrees). All the lesions were treated by surgery (direct clipping 2, wrap-clipping 1), and severe atherosclerotic changes were observed at adjacent arterial walls in all cases. Ordinary wrap-clipping using a polytetrafluoroethylene membrane via the transsylvian approach was difficult because of the limited working space, requiring some special techniques such as usage of fenestrated clips, polyglycolic acid sheets, and combined approach with subtemporal craniotomy. Good clinical outcomes were achieved in 2 patients. CONCLUSION: BBAs at PCoA were predominantly occurred as the small bulges at the origins of wide-angled fetal-type PCoAs in elderly females. Hemodynamic stress and atherosclerosis would contribute to the aneurysmal formation. Wrap-clipping or direct clipping with additional techniques would be useful for this rare condition.

Endothelial cells regulate astrocyte to neural progenitor cell trans-differentiation in a mouse model of stroke.

The concept of the neurovascular unit emphasizes the importance of cell-cell signaling between neural, glial, and vascular compartments. In neurogenesis, for example, brain endothelial cells play a key role by supplying trophic support to neural progenitors. Here, we describe a surprising phenomenon where brain endothelial cells may release trans-differentiation signals that convert astrocytes into neural progenitor cells in male mice after stroke. After oxygen-glucose deprivation, brain endothelial cells release microvesicles containing pro-neural factor Ascl1 that enter into astrocytes to induce their trans-differentiation into neural progenitors. In mouse models of focal cerebral ischemia, Ascl1 is upregulated in endothelium prior to astrocytic conversion into neural progenitor cells. Injecting brain endothelial-derived microvesicles amplifies the process of astrocyte trans-differentiation. Endothelial-specific overexpression of Ascl1 increases the local conversion of astrocytes into neural progenitors and improves behavioral recovery. Our findings describe an unexpected vascular-regulated mechanism of neuroplasticity that may open up therapeutic opportunities for improving outcomes after stroke.

An Adult Case of Sellar Atypical Teratoid/Rhabdoid Tumor Presenting with Lung Metastasis, Harboring a Compound Heterozygous Mutation in INI1.

A typical teratoid/rhabdoid tumors (AT/RT) are highly malignant embryonal tumors in children that are associated with inactivation of the integrase interactor 1 (INI1) gene. Several adult cases of AT/RT have been reported, which were characterized by the sellar occurrence and predominantly occurred in females with INI1 mutation variants. However, clinical and genetic features are poorly understood in this unusual entity. We experienced a case of a 45-year-old female with sellar AT/RT presenting diplopia, who underwent subtotal removal of the tumor by the endoscopic endonasal transsphenoidal approach. Pathological diagnosis was AT/RT with INI1 inactivation on immunohistochemistry. Subsequently, multiple lung metastases were confirmed on fluorodeoxyglucose positron emission tomography (FDG-PET). Although she received postoperative chemoradiotherapy, she died of cerebrospinal fluid dissemination. Autopsy revealed cerebrospinal dissemination and lung metastasis of AT/RT. Biallelic alterations in the INI1 gene were identified by direct sequencing, harboring on different alleles (compound heterozygous mutations) was observed, which is the potential genetic pattern in adult AT/RT. Literature review indicated that lung metastasis frequently occurs in sellar AT/RTs, which is accompanied by cavernous sinus invasion. These observations suggested that cavernous sinus invasion causes haematogenous metastasis to the lung in sellar AT/RT. We discuss clinical and pathological features in adult sellar AT/RT to improve understanding of this unique entity.

Anterior Approach Combined with Endoscopic Fluorescence Video Angiography for a Cervical Perimedullary Arteriovenous Fistula.

BACKGROUND: Perimedullary arteriovenous fistulas (pAVFs) of the anterior cervical spinal cord are rare and difficult to eradicate by surgery because of the limitations of the approach routes. Because of the anatomic relationships, an anterior approach with corpectomy can provide direct observation. However, a narrow corridor to the lesion is the drawback of this approach. Therefore, to overcome this limitation, we introduced angled endoscopes integrated with fluorescence video angiography to observe the real-time blood flow. CASE DESCRIPTION: A 47-year-old woman was incidentally found to have a pAVF fed by multiple radicular arteries, and she underwent direct surgery via the anterior approach. Although observation of the entire lesion was difficult with the microscope alone, the introduction of the angled endoscope made it possible to observe the lateral portion of the spinal cord hidden behind the dura mater. Furthermore, endoscopic fluorescein video angiography visualized residual fine feeding arteries that were then electrocoagulated, which contributed to complete obliteration of the shunt. CONCLUSIONS: The anterior approach with endoscopic assistance is a reasonable strategy for the treatment of ventrally located cervical pAVFs. Furthermore, integration of a fluorescence video angiography system with the endoscope enables confirmation of the complicated real-time hemodynamics of the pAVFs, contributing to reliable treatment.

Embolization of a peripheral cerebral aneurysm associated with intracranial major artery occlusion through a transdural anastomotic artery: Case report.

A peripheral cerebral aneurysm is known to develop at collateral vessels as a result of hemodynamic stress by the occlusion of the intracranial major arteries. We report a case of successful embolization of a ruptured aneurysm through a transdural anastomotic artery. The aneurysm formed at the developed collateral vessel from the meningeal branch of the occipital artery (OA) to the posterior pericallosal artery. A 59-year-old man presented with acute-onset headache, and computed tomography revealed subarachnoid hemorrhage and intracerebral hemorrhage at the splenium of the corpus callosum with intraventricular hemorrhage. Digital subtraction angiography demonstrated a ruptured aneurysm located at a transdural anastomotic artery from the right OA to the posterior pericallosal artery. The patient underwent endovascular treatment for the aneurysm through the transdural anastomotic artery with a coil and n-butyl-2-cyanoacrylate. Because it was impossible to navigate a microcatheter to the aneurysm through the right anterior cerebral artery because of the occlusion of its proximal portion, it was advanced through the transdural anastomosis from the right OA. The aneurysm was completely occluded without complications. Endovascular embolization is a useful treatment option for a peripheral cerebral aneurysm developed at a collateral vessel with intracranial major artery occlusion.