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1.
Interv Neuroradiol ; : 15910199241245279, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38576326

ABSTRACT

OBJECTIVES: This study aimed to evaluate the factors associated with decreasing diffusion-weighted imaging (DWI) positive areas in patients with large early ischemic changes after mechanical thrombectomy (MT). MATERIALS AND METHODS: This retrospective single-center clinical study was conducted between January 2013 and December 2022. We included consecutive patients who underwent MT for acute large-vessel occlusion of the anterior circulation with low pretreatment DWI-Alberta Stroke Program Early Computed Tomography Scores (ASPECTS) (0-5), effective recanalization [thrombolysis in cerebral infarction (TICI) 2b or TICI3], and magnetic resonance imaging (MRI) acquired before and after MT. We measured the DWI-positive area volume before and after MT. The primary endpoint was the after/before-MT DWI-positive area-volume ratio. RESULTS: In total, 28 patients were included in this study. Eight patients (29%) had an after/before-MT DWI-positive area-volume ratio of <1. The median mean apparent diffusion coefficient (ADC) levels of the DWI-positive areas in the groups with a ratio of <1 or >1 were 717 × 106 mm2/s and 637 × 106 mm2/s, respectively (p = 0.011). Multivariate logistic regression analysis showed that ADC level (OR, 1.020 [95% confidence intervals (CIs), 1.001-1.040]; p = 0.040) was an independent predictor of a decreased DWI-positive area after MT. There was a negative correlation between the mean ADC level and the after/before-MT DWI-positive area-volume ratio (p < 0.001, |ρ| = 0.650), and the mean pretreatment ADC cutoff level was 649 × 106 mm2/s (area under the curve (AUC) = 0.806) for predicting a volume ratio of <1. CONCLUSIONS: The mean ADC level before-MT correlated with the after/before-MT DWI-positive area-volume ratio. A mean pretreatment ADC cutoff level of 649 × 106 mm2/s predicted a decreased DWI-positive area after MT.

2.
NMC Case Rep J ; 11: 85-91, 2024.
Article in English | MEDLINE | ID: mdl-38666032

ABSTRACT

Capillary hemangiomas are benign tumors comprising a lobulated proliferation of capillary vessels frequently located in the soft tissues of the neck and head. Spinal intradural capillary hemangiomas are rare, particularly intramedullary lesions. To our knowledge, only 31 cases of spinal intramedullary capillary hemangiomas have been reported. Here, we describe a rare case of a thoracic capillary hemangioma comprising extramedullary and intramedullary components. A 51-year-old male patient presented with bilateral lower extremity numbness and subsequent paraparesis, sensory disturbance, and bladder-bowel dysfunction with a subacute clinical course. Magnetic resonance imaging revealed a mass lesion with intramedullary and intradural extramedullary components at the Th9-10 vertebrae level and widespread spinal cord edema. Contrast-enhanced computed tomography revealed abnormal vessels on the dorsal spinal cord surface. Spinal angiography revealed a light-stained mass lesion fed by the radiculopial artery from the right Th11 intercostal artery. The tumor was resected en bloc, and the histological diagnosis was a capillary hemangioma. Postoperatively, the spinal cord edema diminished, and the patient was discharged from the convalescent rehabilitation ward. Although intramedullary capillary hemangioma is a rare spinal tumor and its preoperative diagnosis is difficult, it should be considered in the differential diagnosis of spinal intramedullary tumors.

3.
Intern Med ; 63(2): 327-331, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-37286508

ABSTRACT

Hidden bow hunter's syndrome (HBHS) is a rare disease in which the vertebral artery (VA) occludes in a neutral position but recanalizes in a particular neck position. We herein report an HBHS case and assess its characteristics through a literature review. A 69-year-old man had repeated posterior-circulation infarcts with right VA occlusion. Cerebral angiography showed that the right VA was recanalized only with neck tilt. Decompression of the VA successfully prevented stroke recurrence. HBHS should be considered in patients with posterior circulation infarction with an occluded VA at its lower vertebral level. Diagnosing this syndrome correctly is important for preventing stroke recurrence.


Subject(s)
Mucopolysaccharidosis II , Stroke , Vertebrobasilar Insufficiency , Male , Humans , Aged , Vertebrobasilar Insufficiency/diagnostic imaging , Vertebrobasilar Insufficiency/etiology , Vertebrobasilar Insufficiency/surgery , Cerebral Angiography/adverse effects , Mucopolysaccharidosis II/complications , Vertebral Artery/diagnostic imaging , Vertebral Artery/surgery , Stroke/complications
4.
Asian J Neurosurg ; 18(3): 651-655, 2023 Sep.
Article in English | MEDLINE | ID: mdl-38152529

ABSTRACT

Parent artery occlusion is a definitive treatment method for preventing rebleeding of dissecting aneurysms. We herein report a case of a ruptured distal posterior inferior cerebellar artery (PICA) dissecting aneurysm treated with internal trapping using n-butyl-2-cyanoacrylate (NBCA). A 65-year-old man visited our hospital with a complaint of headache and neck pain that began 1 week before his arrival. He had a history of spontaneous subarachnoid hemorrhage of unknown cause. Computed tomography of the brain revealed a small amount of subarachnoid hemorrhage, and distal subtraction angiogram showed a distal PICA dissecting aneurysm. We placed a guiding catheter in the left vertebral artery and an intermediate catheter in the PICA. A microcatheter was guided toward the proximal side of the aneurysm and was wedged into the parent artery. The dissecting aneurysm was treated with parent artery occlusion using 50% NBCA. The postoperative course was uneventful, and the patient was discharged 3 weeks after treatment without any neurological deficit. Parent artery occlusion with internal trapping using NBCA could be a safe and definitive treatment method for distal PICA dissecting aneurysms. Angiographical evaluation of the collateral network in the distal branch of PICA before embolization and wedged microcatheter technique in the parent artery are important for successful embolization using NBCA.

5.
J Neurosurg Case Lessons ; 6(14)2023 Oct 02.
Article in English | MEDLINE | ID: mdl-37782959

ABSTRACT

BACKGROUND: In-stent thrombotic occlusion is a serious ischemic complication that can also result in ischemia in the distal perfusion territory and the territory of side branches for the artery in which the flow diverter (FD) stent is deployed. OBSERVATIONS: A 49-year-old female with a large paraclinoid internal carotid artery (ICA) aneurysm was treated with an FD involving the orifice of the anterior cerebral artery (ACA). The antiplatelet dose was reduced because of an increased clopidogrel response postintervention. The patient developed aphasia 2 months later. Emergency magnetic resonance imaging and digital subtraction angiography of the brain indicated FD stent occlusion and a small infarct in the distal vascular territory of the ipsilateral ICA, but the anterior choroidal artery (AChoA) territory was preserved by collateral flow. Emergency superficial temporal artery to middle cerebral artery anastomosis was performed, and she was discharged without neurological deficit 2 weeks after the second operation. LESSONS: In-stent occlusion after FD deployment involving the orifice of the ACA can cause severe cerebral ischemia that requires an adequate antiplatelet effect and careful follow-up. The AChoA territory can be preserved by collateral blood flow even in cases of in-stent occlusion.

6.
J Stroke Cerebrovasc Dis ; 32(6): 107110, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37023536

ABSTRACT

OBJECTIVE: To investigate factors associated with improvements in cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) after combined revascularization surgery for moyamoya disease, with special attention to the size of craniotomy. METHODS: We retrospectively analyzed 35 hemispheres in 27 patients with adult and older pediatric moyamoya disease. CBF and CVR were measured separately in the MCA and ACA territories from acetazolamide-challenged single-photon emission computed tomography before and after 6 months postoperatively, and associations with various factors were analyzed. RESULTS: Postoperative CBF improved in patients with lower preoperative blood flow in both ACA and MCA territories. Postoperative CVR improved in 32 of 35 patients (91.4%) in the MCA territory and in 30 of 35 patients (85.7%) in the ACA territory, with more prominent improvement in the MCA territory than in the ACA territory (MCA territory 29.7% vs ACA territory 21.1%, p = 0.015). Craniotomy area did not correlate with postoperative CBF and only MCA territory was associated with good (≥30%) CVR improvement (odds ratio 9.33, 95% confidence interval 1.91-45.6, p = 0.003). CONCLUSIONS: Postoperative CBF improved in adult and older pediatric cases, reflecting preoperative CBF. Postoperative CVR improved in most cases, although the degree of improvement was more prominent in the MCA territory than in the ACA territory, suggesting a contribution of the temporal muscle. Large craniotomy area was not associated with improved blood flow in the ACA territory and should be applied prudently.


Subject(s)
Cerebral Revascularization , Moyamoya Disease , Adult , Humans , Child , Moyamoya Disease/diagnostic imaging , Moyamoya Disease/surgery , Moyamoya Disease/complications , Retrospective Studies , Cerebrovascular Circulation , Craniotomy/adverse effects , Craniotomy/methods , Cerebral Revascularization/adverse effects , Cerebral Revascularization/methods
7.
World Neurosurg ; 175: e208-e217, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36924889

ABSTRACT

OBJECTIVE: Carotid artery stenting (CAS) is the established treatment strategy of the cervical internal carotid artery (cICA) stenosis, but its use for acute tandem lesions remains controversial. We investigated the clinical and procedural outcomes of management of cICA lesions and evaluated the risk factors for complications. METHODS: Fifty patients who underwent acute mechanical thrombectomy for tandem lesion between January 2014 and June 2022 were included. Treatment of the cICA lesion was classified into the CAS group or the non-CAS group. The risk factors for postoperative ischemic events or symptomatic intracranial hemorrhage (sICH) were analyzed. RESULTS: The CAS group included 36 patients (72%) and the non-CAS group 14 (28%). Postoperative complications were observed in 9 patients (18%). Thromboembolic complications occurred in 4 patients (29%) of the non-CAS group but in 1 patient (3%) of the CAS group. Severe calcification of the cICA (P = 0.04), non-CAS (P = 0.018), and more than 60% residual stenosis (P = 0.016) were significant risk factors associated with thromboembolic complications. sICH occurred in 4 patients (11%) of the CAS group but in none of the non-CAS group. More than 80% stenosis improvement was significantly associated with sICH (P = 0.049). Twenty-nine patients (58%) had a good clinical outcome at 90 days after onset. CONCLUSIONS: Acute CAS is effective for the management for cICA tandem lesions during mechanical thrombectomy, but care not to overextend may be important to reduce the risk of sICH. Severe calcification of the cICA may increase the risk of postoperative thromboembolic complications using non-CAS treatment.


Subject(s)
Carotid Stenosis , Ischemic Stroke , Stroke , Humans , Carotid Stenosis/complications , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/surgery , Ischemic Stroke/surgery , Ischemic Stroke/complications , Stroke/etiology , Stroke/surgery , Constriction, Pathologic/etiology , Treatment Outcome , Stents/adverse effects , Angioplasty/adverse effects , Intracranial Hemorrhages/etiology , Retrospective Studies , Carotid Artery, Internal/diagnostic imaging , Carotid Artery, Internal/surgery
8.
Surg Neurol Int ; 13: 469, 2022.
Article in English | MEDLINE | ID: mdl-36324943

ABSTRACT

Background: When severe aortic stenosis (AS) is concomitant with carotid stenosis, carotid artery stenting (CAS) will become a high-risk procedure because baroreceptor reflex-induced bradycardia and hypotension may cause irreversible circulatory collapse. When carotid stenosis-related misery perfusion is present, the risk of cerebral hyperperfusion syndrome increases after carotid revascularization. We report a case of severe carotid disease concomitant with severe AS successfully treated by a combination of staged angioplasty (SAP) and transcatheter aortic valve implantation (TAVI). Case Description: An 86-year-old man presented with transient deterioration of mental status and sluggish responsiveness continuous from the previous day. Magnetic resonance imaging of the brain revealed a right putaminal infarction, occlusion of the right internal carotid artery (ICA), and severe stenosis of the left ICA. Severe AS was diagnosed and single-photon emission computed tomography showed misery perfusion at the bilateral ICA territories. We performed a staged treatment consisting of SAP for the left carotid stenosis and TAVI. A first-stage carotid angioplasty was performed, followed by TAVI 2 weeks later and second-stage CAS 1 week after that. There were no apparent periprocedural complications throughout the clinical course. Conclusion: Combining SAP and TAVI may be an effective treatment option for severe carotid stenosis with misery perfusion concomitant with severe AS.

9.
World Neurosurg ; 167: 9-16, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36030009

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the course of occluded distal vessels before mechanical thrombectomy (MT) for acute large vessel occlusion (LVO) with non-contrast magnetic resonance imaging (MRI). The variable flip-angle three-dimensional turbo spin-echo (VRFA-3D-TSE) method was used to evaluate the course of occluded distal vessels quickly and clearly in acute LVO cases before MT. METHODS: Patients with acute LVO who were indicated for MT between April 2021 and March 2022 were examined by the VRFA-3D-TSE method to evaluate the distal course of occluded vessels. We included internal carotid artery (ICA) occlusion, M1 occlusion of the middle cerebral artery, and basilar artery (BA) occlusion. Preoperative images were compared to the angiographic findings after recanalization or with follow-up magnetic resonance angiography, and the results were assessed by 2 endovascular treatment specialists as excellent, good, or poor imaging. RESULTS: MT was performed in a total of 27 patients. There were 17 patients with intracranial occlusion of the ICA, M1, and BA. Occlusion was found in the intracranial ICA in 6 patients, the M1 in 7, and the BA in 4. VRFA-3D-TSE MRI was performed in all patients, and the imaging was rated (by the 2assessors) as excellent in 12 of 17 and 14 of 17 cases, good in 5 of 17 and 3 of 17 cases, and poor in 0 of 17 cases. CONCLUSIONS: In patients with acute LVO, VRFA-3D-TSE MRI enabled rapid and good depiction of the course of occluded distal vessels before MT without the use of contrast medium.


Subject(s)
Arterial Occlusive Diseases , Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging/methods , Magnetic Resonance Angiography , Middle Cerebral Artery , Carotid Artery, Internal/diagnostic imaging , Carotid Artery, Internal/surgery , Thrombectomy/methods , Treatment Outcome
10.
J Biochem ; 172(2): 71-78, 2022 Jul 25.
Article in English | MEDLINE | ID: mdl-35512114

ABSTRACT

Ferroptosis, a type of oxidative stress cell death, has been implicated in cell injury in several diseases, and treatments with specific inhibitors have been shown to protect cells and tissues. Here we demonstrated that a treatment with the nitroxide radical, 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), prevented the ferroptotic cell death in an airborne manner. Other TEMPO derivatives and lipophilic antioxidants, such as Trolox and ferrostatin-1, also prevented cell death induced by erastin and RSL3; however, only TEMPO exhibited inhibitory activity from a physically distant location. TEMPO vaporized without decomposing and then dissolved again into a nearby water solution. Volatilized TEMPO inhibited glutamate-induced cell death in mouse hippocampal cell lines and also reduced neuronal cell death in a mouse ischemia model. These results suggest that TEMPO is a unique cell protective agent that acts in a volatility-mediated manner.


Subject(s)
Ferroptosis , Animals , Carbolines/pharmacology , Cell Death , Cyclic N-Oxides/pharmacology , Mice
11.
J Neuroendovasc Ther ; 16(2): 87-92, 2022.
Article in English | MEDLINE | ID: mdl-37502646

ABSTRACT

Objective: We report a case of embolic occlusion of the common carotid artery (CCA) in which a giant thrombus was retrieved using the parallel stent retriever technique. Case Presentation: An 84-year-old woman without anticoagulant therapy despite a history of cardioembolic stroke presented to our hospital because of left hemiparesis after developing sudden vision loss in her right eye. Emergency angiography revealed a giant thrombus in the right CCA. After arresting flow in the CCA using a balloon-guided catheter (BGC), we deployed two stent retrievers in parallel from the internal carotid artery to the CCA, and slowly retrieved them simultaneously under manual aspiration through the BGC. As a result, complete recanalization was achieved. Conclusion: Thrombi causing acute embolic occlusion of the CCA are often too large to be completely retrieved using conventional thrombectomy techniques. The parallel stent retriever technique may be effective in such cases.

12.
World Neurosurg ; 149: e146-e153, 2021 05.
Article in English | MEDLINE | ID: mdl-33621674

ABSTRACT

OBJECTIVE: It is challenging to safely treat blood blister-like aneurysms (BBAs) of the internal carotid artery. Endovascular surgery has been reported, but the optimal strategy is yet to be established. We report our endovascular treatment strategy using the Low-profile Visualized Intraluminal Support (LVIS) stent. METHODS: Twelve patients with ruptured BBAs including 1 patient with 2 separate aneurysmal bulges were treated from December 2017 to January 2020. Single LVIS stent-assisted coil embolization was performed as the initial treatment. If the coil could not be placed in the aneurysm, or follow-up angiography showed persistent filling or regrowth of the aneurysm, a second LVIS stent was deployed as an overlapping stent. Clinical characteristics, treatment details, and clinical outcomes were retrospectively examined. RESULTS: Single stent-assisted coiling was performed in 8 patients (69%), 2 overlapping stents with coiling in 1 (8%), a single stent in 2 (15%), and 2 overlapping stents in 2 (15%). Three patients with persistent filling or regrowth of the aneurysm were re-treated with overlapping stents. Follow-up angiography confirmed complete occlusion in 12 aneurysms (92%). No re-rupture occurred. Postoperative symptomatic ischemia was confirmed in 4 patients (33%), and all 4 patients suffered severe subarachnoid hemorrhage. Modified Rankin scale was 0-2 in 8 patients (67%). CONCLUSIONS: LVIS stent-assisted coil embolization is effective in preventing re-rupture of BBAs. However, the morphology of the aneurysm may change within a short period, so careful angiographic follow-up is needed. Appropriate preoperative antiplatelet administration and optimal timing of the treatment may reduce the risk of postoperative ischemic complication.


Subject(s)
Aneurysm, Ruptured/surgery , Aortic Dissection/surgery , Carotid Artery Injuries/surgery , Carotid Artery, Internal, Dissection/surgery , Endovascular Procedures/methods , Intracranial Aneurysm/surgery , Stents , Adult , Aged , Aged, 80 and over , Carotid Artery Diseases/surgery , Carotid Artery, Internal/surgery , Female , Humans , Male , Middle Aged , Rupture, Spontaneous
13.
J Stroke Cerebrovasc Dis ; 28(2): 325-329, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30415920

ABSTRACT

BACKGROUND: Patients with intracerebral hemorrhage taking anticoagulants are increasingly common in Japan due to the aging population. The clinical benefit of restarting anticoagulants is established, but the optimal timing of resumption is controversial. Risk factors for hemorrhagic and cardioembolic events in the acute phase are also unknown. This study investigated hemorrhagic and cardioembolic events and risk factors in intracerebral hemorrhage patients taking anticoagulants. METHODS: The clinical data of 65 consecutive intracerebral hemorrhage patients taking anticoagulants were retrospectively reviewed. Hemorrhagic and cardioembolic complications and risk factors were analyzed. RESULTS: Lobar hemorrhage was the most frequent (21 of 65 cases, 32.3%). At discharge, 31 patients (47.7%) showed severe disability or had died. Eight (18.6%) of 43 patients who restarted anticoagulants after initial treatment developed hemorrhagic events, including recurrent intracerebral hemorrhage in 3. HAS-BLED score was 2-3 in these 3 patients. Six (15.8%) of 38 patients who took anticoagulants for cardiogenic factors suffered cardioembolism. Systemic inflammatory response syndrome was significantly more common in the cardioembolic group (66.7%) compared with the noncardioembolic group (21.9%, P < .05). CHA2DS2-VASc score was paradoxically high in the noncardioembolic group (3 versus 5, P < .05). CONCLUSION: HAS-BLED score and CHA2DS2-VASc score were not useful for risk assessment for hemorrhagic events, recurrent intracerebral hemorrhage, and cardioembolism in the acute phase. Inflammatory response might be important in the occurrence of cardioembolic events.


Subject(s)
Anticoagulants/adverse effects , Atrial Fibrillation/drug therapy , Cerebral Hemorrhage/chemically induced , Embolism/prevention & control , Age Factors , Aged , Anticoagulants/administration & dosage , Atrial Fibrillation/diagnosis , Atrial Fibrillation/mortality , Cerebral Hemorrhage/diagnosis , Cerebral Hemorrhage/mortality , Cerebral Hemorrhage/therapy , Clinical Decision-Making , Decision Support Techniques , Disability Evaluation , Drug Administration Schedule , Embolism/diagnosis , Embolism/mortality , Female , Hospital Mortality , Humans , Japan/epidemiology , Male , Predictive Value of Tests , Prevalence , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome
14.
Neuropathology ; 38(5): 498-502, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29869356

ABSTRACT

A 40-year-old man was admitted to our hospital because of disorientation and mild left-sided weakness. Radiological examination revealed a solid and cystic tumor in the right temporal lobe, and total resection was performed. Histologically, the tumor was composed mainly of low-grade gangiloglioma and had some high-grade glial components with focal necrosis and microvascular proliferations. In the high-grade component, there were epithelioid cells with round cytoplasm and eccentric nuclei. The high-grade area with epithelioid cells was intermingled within the low-grade area, which suggests that epithelioid cells were an anaplastic transformation of ganglioglioma. The epithelioid cells were histologically similar to neoplastic cells of epithelioid glioblastoma (E-GBM), a rare aggressive variant of isocitric dehydrogenase wild-type glioblastoma. A BRAF V600E mutation, frequently observed in E-GBM, was detected in both the ganglioglioma and epithelioid cell components. The epithelioid cells were mitotically active, which suggests that if the surgery was delayed, the histological appearance might have eventually evolved into E-GBM. Indeed, a case of pleomorphic xanthoastrocytoma which transformed into E-GBM after a long latency was reported elsewhere. This is the first report to describe focal epithelioid cells in anaplastic ganglioglioma.


Subject(s)
Brain Neoplasms/pathology , Epithelioid Cells/pathology , Ganglioglioma/pathology , Adult , Humans , Male , Temporal Lobe/pathology
15.
Asian J Neurosurg ; 13(2): 462-464, 2018.
Article in English | MEDLINE | ID: mdl-29682061

ABSTRACT

We experienced a case of sphenoid sinus type meningoencephalocele manifesting as severe cerebrospinal fluid (CSF) rhinorrhea. A 35-year-old man became aware of serous nasal discharge 1 year previously, which had gradually worsened. The nasal discharge was diagnosed as CSF rhinorrhea. Head computed tomography (CT) showed several small depressions in the bone of the left middle cranial fossa, and the largest depression extended through the bone to the lateral sphenoid sinus. Head magnetic resonance imaging revealed that the meningoencephalocele projected to the lateral sphenoid sinus, through this small bone defect of the middle cranial fossa. We performed a combined craniotomy and epidural approach without intradural procedures using neuronavigation. Multiple meningoencephaloceles protruded into small depressions in the middle skull base. The small protrusions not passing through the sphenoid sinus were coagulated. The largest protrusion causing the CSF leakage was identified by neuronavigation. This meningoencephalocele was cut. Both the dural and bone sides were closed with double layers to prevent CSF leakage. The CSF rhinorrhea completely stopped after the surgery. In our case, identification of the leak site was easy with neuronavigation based on bone window CT. The epidural approach also has significant advantages with double layer closure, including both the dural and bone sides. If the site of CSF leakage is outside the foramen rotundum (as with the most common type of lateral sphenoid sinus meningoencephalocele), we recommend the epidural approach using neuronavigation for surgical treatment.

16.
Cancer Sci ; 108(11): 2187-2194, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28837253

ABSTRACT

In cancer cells the small compounds erastin and RSL3 promote a novel type of cell death called ferroptosis, which requires iron-dependent accumulation of lipid reactive oxygen species. Here we assessed the contribution of lipid peroxidation activity of lipoxygenases (LOX) to ferroptosis in oncogenic Ras-expressing cancer cells. Several 12/15-LOX inhibitors prevented cell death induced by erastin and RSL3. Furthermore, siRNA-mediated silencing of ALOX15 significantly decreased both erastin-induced and RSL3-induced ferroptotic cell death, whereas exogenous overexpression of ALOX15 enhanced the effect of these compounds. Immunofluorescence analyses revealed that the ALOX15 protein consistently localizes to cell membrane during the course of ferroptosis. Importantly, treatments of cells with ALOX15-activating compounds accelerated cell death at low, but not high doses of erastin and RSL3. These observations suggest that tumor ferroptosis is promoted by LOX-catalyzed lipid hydroperoxide generation in cellular membranes.


Subject(s)
Arachidonate 15-Lipoxygenase/genetics , Cell Death/drug effects , Fibrosarcoma/genetics , Pancreatic Neoplasms/genetics , Carbolines/administration & dosage , Cell Line, Tumor , Fibrosarcoma/drug therapy , Fibrosarcoma/pathology , Gene Expression Regulation, Neoplastic/drug effects , Humans , Lipid Peroxidation/drug effects , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Piperazines/administration & dosage , RNA, Small Interfering , Pancreatic Neoplasms
17.
Biochem J ; 473(6): 769-77, 2016 Mar 15.
Article in English | MEDLINE | ID: mdl-26759376

ABSTRACT

Pharmacological challenges to oncogenic Ras-expressing cancer cells have shown a novel type of cell death, ferroptosis, which requires intracellular iron. In the present study, we assessed ferroptosis following treatment of human fibrosarcoma HT1080 cells with several inhibitors of lysosomal activity and found that they prevented cell death induced by the ferroptosis-inducing compounds erastin and RSL3. Fluorescent analyses with a reactive oxygen species (ROS) sensor revealed constitutive generation of ROS in lysosomes, and treatment with lysosome inhibitors decreased both lysosomal ROS and a ferroptotic cell-death-associated ROS burst. These inhibitors partially prevented intracellular iron provision by attenuating intracellular transport of transferrin or autophagic degradation of ferritin. Furthermore, analyses with a fluorescent sensor that detects oxidative changes in cell membranes revealed that formation of lipid ROS in perinuclear compartments probably represented an early event in ferroptosis. These results suggest that lysosomal activity is involved in lipid ROS-mediated ferroptotic cell death through regulation of cellular iron equilibria and ROS generation.


Subject(s)
Cell Death/physiology , Iron/metabolism , Lysosomes/physiology , Aspartic Acid Proteases/antagonists & inhibitors , Cell Line, Tumor , Deferoxamine/pharmacology , Humans , Pepstatins/pharmacology , Piperazines/pharmacology , Reactive Oxygen Species
18.
Acta Neurochir (Wien) ; 155(4): 607-9, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23430235

ABSTRACT

BACKGROUND: Superficial temporal artery-to-middle cerebral artery (STA-MCA) anastomosis is a common procedure for neurosurgeons. The surgery necessarily requires accurate and speedy manipulation of microscope, for which a specific training is needed. Unexpected bypass occlusion sometimes happen during surgery. OBJECTIVE: Generally, conventional interrupted or continuous suture has been used for vascular anastomosis, despite various ideas have been attempted in the other surgery fields. We propose a horizontal mattress suture technique for intracranial microvascular bypass surgery. This is the first report ever published on intracranial vascular anastomosis. METHODS: We had four patients of STA-MCA bypass surgery with "mattress anastomosis" from March to May of 2012. RESULTS: During the procedure, there was no bypass occlusion and good patency was confirmed in all cases. CONCLUSION: Intimae of the recipient and the donor blood vessel contact each other precisely with this technique. Although a long-term assessment of patency is needed, it is useful for the intracranial bypass surgery.


Subject(s)
Anastomosis, Surgical , Cerebral Revascularization/methods , Intracranial Aneurysm/surgery , Middle Cerebral Artery/surgery , Temporal Arteries/surgery , Anastomosis, Surgical/methods , Cerebral Angiography/methods , Humans , Intracranial Aneurysm/diagnostic imaging , Middle Cerebral Artery/diagnostic imaging , Temporal Arteries/diagnostic imaging , Treatment Outcome
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