Publications by authors named "Yukihiko Fujii"

204 Publications

Phosphorylation of GAP-43 T172 is a molecular marker of growing axons in a wide range of mammals including primates.

Mol Brain 2021 Apr 8;14(1):66. Epub 2021 Apr 8.

Departments of Neurochemistry and Molecular Cell Biology, School of Medicine and Graduate School of Medical/Dental Sciences, Niigata University, Niigata, 951-8510, Japan.

GAP-43 is a vertebrate neuron-specific protein and that is strongly related to axon growth and regeneration; thus, this protein has been utilized as a classical molecular marker of these events and growth cones. Although GAP-43 was biochemically characterized more than a quarter century ago, how this protein is related to these events is still not clear. Recently, we identified many phosphorylation sites in the growth cone membrane proteins of rodent brains. Two phosphorylation sites of GAP-43, S96 and T172, were found within the top 10 hit sites among all proteins. S96 has already been characterized (Kawasaki et al., 2018), and here, phosphorylation of T172 was characterized. In vitro (cultured neurons) and in vivo, an antibody specific to phosphorylated T172 (pT172 antibody) specifically recognized cultured growth cones and growing axons in developing mouse neurons, respectively. Immunoblotting showed that pT172 antigens were more rapidly downregulated throughout development than those of pS96 antibody. From the primary structure, this phosphorylation site was predicted to be conserved in a wide range of animals including primates. In the developing marmoset brainstem and in differentiated neurons derived from human induced pluripotent stem cells, immunoreactivity with pT172 antibody revealed patterns similar to those in mice. pT172 antibody also labeled regenerating axons following sciatic nerve injury. Taken together, the T172 residue is widely conserved in a wide range of mammals including primates, and pT172 is a new candidate molecular marker for growing axons.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13041-021-00755-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034164PMC
April 2021

[Proton magnetic resonance spectroscopy (H-MRS)].

No Shinkei Geka 2021 Mar;49(2):438-444

Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata.

Proton magnetic resonance spectroscopy(H-MRS)is a non-invasive method for evaluating brain function and metabolism. H-MRS can quantify low-molecular-weight metabolites in a living brain; it shows their spectra without tracer administration. In this paper, we introduce H-MRS and MRS for imaging the distribution of metabolites. The applications of H-MRS imaging for several neurological disorders will be outlined.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11477/mf.1436204411DOI Listing
March 2021

[Dysplastic Cerebellar Gangliocytoma(Lhermitte-Duclos Disease)].

No Shinkei Geka 2021 Mar;49(2):395-399

Department of Translational Research, Brain Research Institute, Niigata University.

Dysplastic cerebellar gangliocytoma or Lhermitte-Duclos disease(LDD)is a rare benign cerebellar lesion composed of dysplastic ganglion cells that conform to the existing cortical architecture. In this disease, the enlarged ganglion cells are predominantly located within the internal granular layer, and they thicken the cerebellar folia. The architecture of the affected cerebellar hemisphere with the enlarged cerebellar folia and the cystic changes, in some cases, present as "tiger-striped striations," a characteristic imaging finding that is not specific to LDD. This imaging feature may be observed in medulloblastoma and isolated cerebellar Rosai-Dorfman disease. This cerebellar lesion is a major central nervous system manifestation of Cowden syndrome, an autosomal dominant condition that causes various hamartomas and neoplasms. A molecular-based study estimated the prevalence of Cowden syndrome to be 1 case per 200,000. In a study involving 211 patients with Cowden syndrome, 32% developed LDD. LDD can be diagnosed in young children and older adults within the eighth decades of life. PTEN mutations have been identified in virtually all adult-onset LDDs, but not in childhood-onset cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11477/mf.1436204404DOI Listing
March 2021

[Melanocytic Tumors].

No Shinkei Geka 2021 Mar;49(2):389-394

Department of Translational Research, Brain Research Institute, Niigata University.

Primary melanocytic neoplasms of the central nervous system(CNS)presumably arise from leptomeningeal melanocytes that are derived from the neural crest. Melanocytic neoplasms associated with neurocutaneous melanosis likely derive from melanocyte precursor cells that reach the CNS after somatic mutations, mostly, of the . They should be distinguished from other melanotic tumors involving the CNS, including metastatic melanoma and other primary tumors that undergo melanization, such as melanocytic schwannomas, medulloblastomas, paragangliomas, and various gliomas, because these lesions require different patient workups and therapy. Primary melanocytic neoplasms of the CNS that are diffuse and do not form macroscopic masses are called melanocytoses, whereas malignant diffuse or multifocal lesions are collectively called melanomatoses. Benign and intermediate-grade tumoral lesions are called melanocytomas. Discrete malignant tumors are called melanomas. CT and MRI of melanocytosis and melanomatosis show diffuse thickening and enhancement of the leptomeninges, often with focal or multifocal nodularity. Depending on the melanin content, diffuse and circumscribed melanocytic tumors of the CNS may show some characteristics on CT and MRI: iso- to hyperattenuation on CT and paramagnetic properties of melanin on MRI resulting in an isointense signal on T1WIs and iso- to hypointensity on T2WIs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11477/mf.1436204403DOI Listing
March 2021

[Multinodular and Vacuolating Neuronal Tumor of the Cerebrum(MVNT)].

No Shinkei Geka 2021 Mar;49(2):383-387

Department of Translational Research, Brain Research Institute, Niigata University.

Multinodular and vacuolating neuronal tumors of the cerebrum(MVNTs)are rare brain tumors that were described first in 2013. MVNTs have been added to the World Health Organization Classification of Tumors of the Central Nervous System in 2016(2016WHO), although an MVNT is a clinical-pathological lesion with uncertain class assignment. It remains unclear whether MVNTs should be considered a true neoplasm or malformative lesion. Their prevalence and pathophysiology are unknown. MVNTs typically occur in adults, predominantly in the cerebral subcortical region, and are most frequently associated with seizures or seizure equivalents. MVMTs can also present incidentally without seizures. MVNTs have been reported to show highly suggestive imaging features, especially on MRI scans. MVNTs consist of small T2 and T2-FLAIR hyperintense nodules in subcortical and juxtacortical areas with rare or no post-contrast enhancement. Most MVNTs reported in the literature involve the supratentorial part of the brain. Recently, lesions exhibiting a remarkably similar pattern of imaging findings were described in the posterior fossa, which are referred to as multinodular and vacuolating posterior fossa of unknown significance(MV-PLUS). Both MVNT and MV-PLUS are considered "leave-me-alone" lesions because of the absence of malignancy criteria and the lack of evolutivity on follow-up MRI scans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11477/mf.1436204402DOI Listing
March 2021

Topoisomerase IIβ immunoreactivity (IR) co-localizes with neuronal marker-IR but not glial fibrillary acidic protein-IR in GLI3-positive medulloblastomas: an immunohistochemical analysis of 124 medulloblastomas from the Japan Children's Cancer Group.

Brain Tumor Pathol 2021 Apr 11;38(2):109-121. Epub 2021 Mar 11.

Department of Neuropathology, Aichi Medical University, Institute for Medical Science of Aging, Aichi, Japan.

We previously reported observing GLI3 in medulloblastomas expressing neuronal markers (NM) and/or glial fibrillary acidic protein (GFAP). Furthermore, patients with medulloblastomas expressing NM or GFAP tended to show favorable or poor prognosis, respectively. In the present study, we focused on the role of topoisomerase IIβ (TOP2β) as a possible regulator for neuronal differentiation in medulloblastomas and examined the pathological roles of GLI3, NM, GFAP, and TOP2β expressions in a larger population. We divided 124 medulloblastomas into three groups (NM-/GFAP-, NM +/GFAP-, and GFAP +) based on their immunoreactivity (IR) against NM and GFAP. The relationship among GLI3, NM, GFAP, and TOP2β was evaluated using fluorescent immunostaining and a publicly available single-cell RNA sequencing dataset. In total, 87, 30, and 7 medulloblastomas were classified as NM-/GFAP-, NM + /GFAP-, and GFAP +, and showed intermediate, good, and poor prognoses, respectively. GLI3-IR was frequently observed in NM +/GFAP-  and GFAP + , and TOP2β-IR was frequently observed only in NM +/GFAP-  medulloblastomas. In fluorescent immunostaining, TOP2β-IR was mostly co-localized with NeuN-IR but not with GFAP-IR. In single-cell RNA sequencing, TOP2β expression was elevated in CMAS/DCX-positive, but not in GFAP-positive, cells. NM-IR and GFAP-IR are important for estimating the prognosis of patients with medulloblastoma; hence they should be assessed in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10014-021-00396-0DOI Listing
April 2021

Hemodynamic features of an intracranial aneurysm rupture predicted by perianeurysmal edema: A case report.

Surg Neurol Int 2021 10;12:49. Epub 2021 Feb 10.

Department of Neurosurgery, Niigata University, Brain Research Institute, Niigata, Japan.

Background: Perianeurysmal edema (PAE) has been suggested as an indicator of potential aneurysm rupture; however, the hemodynamic features of these aneurysms are still unknown. A computational fluid dynamic (CFD) analysis was performed to evaluate the hemodynamic features of a very rare case of a ruptured middle cerebral artery (MCA) aneurysm with PAE.

Case Description: A 65-year-old woman presented with disturbed consciousness. A subarachnoid hemorrhage due to an azygos anterior cerebral artery (ACA) aneurysm rupture was suspected. An unruptured MCA aneurysm with PAE was identified in the left temporal lobe. Although the ACA aneurysm was clipped to prevent re-bleeding, the MCA aneurysm subsequently ruptured 6 days later. Clipping of the MCA aneurysm was performed, and hemosiderin deposits suggestive of sentinel bleeding were found on the surface of the aneurysm dome. CFD analysis revealed unstable hemodynamic stress at the expanded bleb area after rupture, localized to the rupture site. Moreover, this analysis revealed flow impingement with pressure elevation and low wall shear stress, which indicated increased inflammation and aneurysm wall thinning that likely led to rupture.

Conclusion: Hemosiderin deposits at the aneurysm wall and PAE indicates leakage from a cerebral aneurysm. Hemodynamic stress at the aneurysm may promote an inflammatory response and lead to wall weakening accompanied by PAE. Based on our findings, we recommend that surgical intervention should be considered as the first line of treatment for such aneurysms to prevent rupture.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.25259/SNI_780_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911146PMC
February 2021

Delayed Bleeding of Unruptured Intracranial Aneurysms After Coil Embolization: A Retrospective Case Series.

World Neurosurg 2021 Feb 20. Epub 2021 Feb 20.

Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Japan.

Objective: Delayed bleeding of unruptured intracranial aneurysms (UIAs) after coil embolization is rare; this study aimed to analyze the occurrence of delayed bleeding of UIAs after coil embolization.

Methods: We retrospectively analyzed patients with UIAs after coil embolization between January 2002 and December 2018 and assessed the features of UIAs with delayed bleeding after coil embolization.

Results: Analysis included 307 patients with 335 UIAs. Mean follow-up was 7.1 ± 4.9 years, and total follow-up was 2365 aneurysm-years. There were 271 (80.9%) aneurysms located in the anterior circulation and 64 (19.1%) aneurysms located in the posterior circulation. Significant differences were observed between the 2 groups in terms of maximum size of the aneurysm (P < 0.01), width of the aneurysm neck (P < 0.01), and number of retreatment cases (P < 0.01). During the follow-up period, delayed bleeding occurred in 4 aneurysms (annual bleeding rate of 0.17%); all were located in the posterior circulation. The original size was not relatively large (mean 8.6 ± 2.4 mm). All aneurysms bled within 5 years (mean 35 ± 9.6 months) after the initial treatment. Two were de novo aneurysms that developed adjacent to the coiled aneurysms and were not detected on follow-up magnetic resonance angiography.

Conclusions: Cautious follow-up of UIAs with digital subtraction angiography is important, articularly within the first 5 years after the procedure. If there are changes in the anatomic outcomes, short-term reassessment or additional treatment should be actively considered, particularly for aneurysms in the posterior circulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2021.02.061DOI Listing
February 2021

Prospective, Multicenter Clinical Study of Microvascular Decompression for Hemifacial Spasm.

Neurosurgery 2021 03;88(4):846-854

Seikei-kai Chiba Medical Center, Chiba, Japan.

Background: Microvascular decompression (MVD) is the most effective procedure for hemifacial spasm (HFS). MVD results from nonspecialized or low-volume institutes are not always reliable. Most studies on MVD for HFS are retrospective and single centered; to the best of our knowledge, no prospective, multicenter studies exist.

Objective: To evaluate short- and long-term outcomes and complications in patients who underwent MVD for HFS in specialized Japanese institutions, in this multicenter, prospective, cohort study.

Methods: Included patients had undergone MVD for HFS in study centers between April 2012 and March 2015. Patients' postoperative grade of involuntary movements and complications were recorded postoperatively at 7 d (short-term) and at 1 (mid-term) and 3 (long-term) yr.

Results: A total of 486 patients (150 men, 336 women; mean age 53.9 yr with 181 patients over 60 yr) were enrolled during the study period. Neuromonitoring was used in 96.3% of the cases. The complete cure rate of symptom relief, mortality rate, and complication rate at short-term follow-up were 70.6%, 0%, and 15%, respectively. The long-term follow-up was completed by 463 patients (95.3%); the complete cure rate of symptom relief and complication rate were 87.1% and 3.0%, respectively.

Conclusion: Our study revealed that under expert guidance and intraoperative neuromonitoring, the long-term curative effect rate of MVD for HFS is high, while complications are uncommon and usually transient. Our results indicate that MVD is an effective and safe treatment for patients with HFS, including elderly patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuros/nyaa549DOI Listing
March 2021

Possibility of Worsening Flow Diversion Effect Due to Morphological Changes of a Stented Artery With Multiple Overlapping Stents for Partially Thrombosed Vertebral Artery Aneurysms.

Front Neurol 2020 15;11:611124. Epub 2020 Dec 15.

Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Japan.

Morphological changes of a stented artery can cause a flow diversion effect to reduce intra-aneurysmal flow; however, there is a potential for the negative effect of increased intra-aneurysmal flow. We present cases with multiple overlapping stents for a partially thrombosed vertebral artery aneurysm and characterize the hemodynamic properties of a recurrent case by focusing on the morphological changes of the stented artery. Between October 2017 and April 2019, four consecutive cases of symptomatic unruptured large and giant partially thrombosed vertebral artery aneurysms were treated with multiple overlapping low-profile visualized intraluminal support stents and no coils. Both angiographic and clinical outcomes were assessed. Computational fluid dynamics analysis was performed to clarify hemodynamic features. The degree of pressure elevation was calculated as the pressure difference (Pd). Wall shear stress (WSS) was also calculated. In three of the four cases, successful flow reduction was achieved with no morphological change of the stented arteries. The patients' symptoms were gradually improved. The remaining case required additional stents after the initial treatment. In the recurrent case, Pd was noticeably elevated at the aneurysm neck after treatment, and WSS was generally increased in the area due to altered blood flow into the aneurysm dome caused by morphological changes of the stented artery. Overlapping stents can be used for the treatment of large and giant thrombosed vertebral artery aneurysms with flow diversion effect; however, morphological changes of the stented artery requires careful attention as it may lead to an increase in the intra-aneurysmal flow, causing negative outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2020.611124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770215PMC
December 2020

GLI3 Is Associated With Neuronal Differentiation in SHH-Activated and WNT-Activated Medulloblastoma.

J Neuropathol Exp Neurol 2021 Jan;80(2):129-136

Department of Pathology, Brain Research Institute, Niigata University.

Glioma-associated oncogene homolog 3 (GLI3), whose main function is to inhibit GLI1, has been associated with neuronal differentiation in medulloblastoma. However, it is not clear what molecular subtype(s) show increased GLI3 expression. GLI3 levels were assessed by immunohistochemistry in 2 independent cohorts, including a total of 88 cases, and found to be high in both WNT- and SHH-activated medulloblastoma. Analysis of bulk mRNA expression data and single cell RNA sequencing studies confirmed that GLI1 and GLI3 are highly expressed in SHH-activated medulloblastoma, whereas GLI3 but not GLI1 is highly expressed in WNT-activated medulloblastoma. Immunohistochemical analysis has shown that GLI3 is expressed inside the neuronal differentiated nodules of SHH-activated medulloblastoma, whereas GLI1/2 are expressed in desmoplastic areas. In contrast, GLI3 is diffusely expressed in WNT-activated medulloblastoma, whereas GLI1 is suppressed. Our data suggest that GLI3 may be a master regulator of neuronal differentiation and morphology in these subgroups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jnen/nlaa141DOI Listing
January 2021

Proteomic profile differentiating between mesial temporal lobe epilepsy with and without hippocampal sclerosis.

Epilepsy Res 2020 12 6;168:106502. Epub 2020 Nov 6.

Department of Pathology, Aichi Developmental Disability Center, Japan; Pathology Research Team, Faculty of Health Sciences, Kyorin University, Japan. Electronic address:

Hippocampal sclerosis (HS) is the most common neuropathological condition in adults with drug-resistant epilepsy and represents a critical feature in mesial temporal lobe epilepsy (MTLE) syndrome. Although epileptogenic brain tissue is associated with glutamate excitotoxicity leading to oxidative stress, the proteins that are targets of oxidative damage remain to be determined. In the present study we designed comprehensive analyses of changes in protein expression level and protein oxidation status in the hippocampus or neocortex to highlight proteins associated with excitotoxicity by comparing MTLE patients with relatively mild excitotoxicity (MTLE patients without HS, MTLE-non-HS) and those with severe excitotoxicity (MTLE patients with HS, MTLE-HS). We performed 2-dimensional fluorescence difference gel electrophoresis, 2D-oxyblot analysis, and mass spectrometric amino acid sequencing. We identified 16 proteins at 18 spots in which the protein expression levels differed between sclerotic and non-sclerotic hippocampi. In the sclerotic hippocampus, the expression levels of several synaptic proteins were decreased, and those of some glia-associated proteins increased. We confirmed histologically that all MTLE-HS cases examined exhibited severe neuronal cell loss and remarkable astrocytic gliosis in the hippocampi. In all MTLE-non-HS cases examined, neurons were spared and gliosis was unremarkable. Therefore, we consider that decreased synaptic proteins are a manifestation of loss of neuronal cell bodies and dendrites, whereas increased glia-associated proteins are a manifestation of proliferation and hypertrophy of astrocytes. These are considered to be the result of hippocampal sclerosis. In contrast, the expression level of d-3-phosphoglycerate dehydrogenase (PHGDH), an l-serine synthetic enzyme expressed exclusively by astrocytes, was decreased, and that of stathmin 1, a neurite extension-related protein expressed by neurons, was increased in the sclerotic hippocampus. These findings cannot be explained solely as the result of hippocampal sclerosis. Rather, these changes can be involved in the continuation of seizure disorders in MTLE-HS. In addition, the protein carbonylation detection, an indicator of protein oxidation caused by excitotoxicity of multiple seizures and/or status epilepticus, revealed that the carbonyl level of collapsin response mediator protein 2 (CRMP2) increased significantly in the sclerotic hippocampus. In conclusion, protein identification following profiling of protein expression levels and detection of oxidative proteins indicated potential pathognomonic protein changes. The decreased expression of PHGDH, increased expression of stathmin 1, and carbonylation of CRMP2 differentiate between MTLE with and without HS. Therefore, further investigations of PHGDH, stathmin 1 and CRMP2 are promising to study more detailed effects of excitotoxicity on epileptogenic hippocampal tissue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eplepsyres.2020.106502DOI Listing
December 2020

Unilateral oculomotor nerve palsy caused by arterial compression accompanying subarachnoid hemorrhage: a case report.

Acta Neurochir (Wien) 2021 03 5;163(3):813-816. Epub 2020 Nov 5.

Department of Neurosurgery, Brain Research Institute, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, Niigata, 951-8585, Japan.

Unilateral oculomotor nerve palsy, often caused by aneurysmal compression, is one of the decisive findings for confirming the site of a ruptured aneurysm. However, arterial compression can also cause unilateral oculomotor nerve palsy. Here, we present the case of a 59-year-old woman with a ruptured right internal carotid-posterior communicating artery aneurysm accompanied by contralateral oculomotor nerve palsy. The nerve was found to be compressed by the posterior cerebral artery and was isolated from the ruptured aneurysm. When confirming a ruptured aneurysm based on the evidence of unilateral oculomotor palsy, the arteries surrounding the nerve must be thoroughly assessed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00701-020-04633-xDOI Listing
March 2021

Molecular Features and Prognostic Factors of Pleomorphic Xanthoastrocytoma: A Collaborative Investigation of the Tohoku Brain Tumor Study Group.

Neurol Med Chir (Tokyo) 2020 Nov 16;60(11):543-552. Epub 2020 Oct 16.

Department of Neurosurgery, Faculty of Medicine, Yamagata University.

Pleomorphic xanthoastrocytoma (PXA) is a rare glial tumor, however, its histological differentiation from high-grade gliomas is often difficult. Molecular characteristics may contribute to a better diagnostic discrimination. Prognostic factors of PXA are also important but few relevant reports have been published. This study investigated the molecular features and prognostic factors of PXAs. Seven university hospitals participated in this study by providing retrospective clinical data and tumor samples of PXA cases between 1993 and 2014. Tumor samples were analyzed for immunohistochemical (IHC) neuronal and glial markers along with Ki67. The status of the BRAF and TERT promoter (TERTp) mutation was also evaluated using the same samples, followed by feature extraction of PXA and survival analyses. In all, 19 primary cases (17 PXA and 2 anaplastic PXA) were included. IHC examination revealed the stable staining of nestin and the close association of synaptophysin to NFP. Of the PXA cases, 57% had the BRAF mutation and only 7% had the TERTp mutation. On univariate analysis, age (≥60 years), preoperative Karnofsky performance status (KPS) (≤80%), and marked peritumoral edema were significantly associated with progression-free survival (PFS). No independent factor was indicated by the multivariate analysis. In conclusion, PXA was characterized by positive nestin staining and a few TERTp mutations. The neuronal differential marker and BRAF status may help in diagnosis. Patient age, preoperative KPS, and marked perifocal edema were associated with PFS. The present study is limited because of small number of cases and its retrospective nature. Further clinical study is needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2176/nmc.oa.2020-0155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788268PMC
November 2020

A Hyperactive RelA/p65-Hexokinase 2 Signaling Axis Drives Primary Central Nervous System Lymphoma.

Cancer Res 2020 12 16;80(23):5330-5343. Epub 2020 Oct 16.

Department of Neurosurgery, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.

Primary central nervous system lymphoma (PCNSL) is an isolated type of lymphoma of the central nervous system and has a dismal prognosis despite intensive chemotherapy. Recent genomic analyses have identified highly recurrent mutations of MYD88 and CD79B in immunocompetent PCNSL, whereas LMP1 activation is commonly observed in Epstein-Barr virus (EBV)-positive PCNSL. However, a lack of clinically representative preclinical models has hampered our understanding of the pathogenic mechanisms by which genetic aberrations drive PCNSL disease phenotypes. Here, we establish a panel of 12 orthotopic, patient-derived xenograft (PDX) models from both immunocompetent and EBV-positive PCNSL and secondary CNSL biopsy specimens. PDXs faithfully retained their phenotypic, metabolic, and genetic features, with 100% concordance of MYD88 and CD79B mutations present in PCNSL in immunocompetent patients. These models revealed a convergent functional dependency upon a deregulated RelA/p65-hexokinase 2 signaling axis, codriven by either mutated MYD88/CD79B or LMP1 with Pin1 overactivation in immunocompetent PCNSL and EBV-positive PCNSL, respectively. Notably, distinct molecular alterations used by immunocompetent and EBV-positive PCNSL converged to deregulate RelA/p65 expression and to drive glycolysis, which is critical for intracerebral tumor progression and FDG-PET imaging characteristics. Genetic and pharmacologic inhibition of this key signaling axis potently suppressed PCNSL growth and . These patient-derived models offer a platform for predicting clinical chemotherapeutics efficacy and provide critical insights into PCNSL pathogenic mechanisms, accelerating therapeutic discovery for this aggressive disease. SIGNIFICANCE: A set of clinically relevant CNSL xenografts identifies a hyperactive RelA/p65-hexokinase 2 signaling axis as a driver of progression and potential therapeutic target for treatment and provides a foundational preclinical platform. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/23/5330/F1.large.jpg.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-20-2425DOI Listing
December 2020

[Endovascular Revascularization for Acute Ischemic Stroke Related to Blunt Carotid Injury:A Case Report].

No Shinkei Geka 2020 Jun;48(6):527-532

Department of Neurosurgery, Brain Research Institute, Niigata University.

Although blunt carotid artery injury is known as an important cause of ischemic stroke, the role of the endovascular treatment for acute ischemic stroke related to blunt carotid injuries remains unclear. We report the case of a patient with acute ischemic stroke secondary to blunt carotid artery injury who was treated with endovascular revascularization. A 46-year-old man suffered from sudden left-sided hemiparesis a day after a strike from a Japanese fencing staff on his right neck. 3D-CT angiography revealed tandem internal carotid artery occlusions of the cervical and C1 portions. We performed endovascular revascularization with carotid artery stenting and direct aspiration of the thrombus and achieved complete recanalization. The patient recovered almost completely. We conclude that endovascular revascularization should not be withheld from patients with acute ischemic stroke related to blunt carotid injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11477/mf.1436204223DOI Listing
June 2020

Safety and feasibility of the distal transradial approach: A novel technique for diagnostic cerebral angiography.

Interv Neuroradiol 2020 Dec 13;26(6):713-718. Epub 2020 May 13.

Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Japan.

Purpose: We aimed to evaluate the safety and feasibility of the distal transradial approach (DTRA) as a novel technique for cerebral angiography based on our institutional initial experience.

Methods: We retrospectively analyzed our institutional database of consecutive diagnostic cerebral angiographies performed with DTRA from December 2018 to August 2019. Patient demographics and clinical and procedural data were recorded.

Results: In total, 51 diagnostic cerebral angiographies in 51 patients (age, 15-83 years; mean age, 59.4 years, SD 13.5; 35 (69%) females) were performed or attempted with DTRA. Ultrasound evaluation showed that the mean inner distal radial artery diameter was significantly smaller than the mean inner forearm radial artery diameter (2.19 mm vs. 2.56 mm, P < 0.001). Cannulation via the distal radial artery was successful in 47 (92%) procedures. In the four procedures that failed, operators converted to the ipsilateral transradial approach without repositioning or redraping. Selective catheterization of the intended vessel was achieved in 64 (91%) of 70 vessels. In the remaining six, operators achieved the objective of the examination with angiography injecting from proximal and conversion to another approach was not required. One patient experienced temporary numbness around the puncture site after the procedure. No radial artery occlusion was identified in the patients who underwent ultrasound evaluation.

Conclusion: Our results demonstrate that DTRA could become a standard approach for diagnostic cerebral angiography owing to the low complication rate and the high cannulation success rate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1591019920925709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724605PMC
December 2020

The Japan Neurosurgical Database: Overview and Results of the First-year Survey.

Neurol Med Chir (Tokyo) 2020 Apr 31;60(4):165-190. Epub 2020 Mar 31.

Department of Neurosurgery, Juntendo University Faculty of Medicine.

The Japan Neurosurgical Database (JND) is a prospective observational study registry established in 2017 by the Japan Neurosurgical Society (JNS) to visualize real-world clinical practice, promote science, and improve the quality of care and neurosurgery board certification in Japan. We summarize JND's aims and methods, and describes the 2018 survey results. The JND registered in-hospital patients' clinical data mainly from JNS training institutions in 2018. Caseload, patient demographics, and in-hospital outcomes of the overall cohort and a neurosurgical subgroup were examined according to major classifications of main diagnosis. Neurosurgical caseload per neurosurgeon in training in core hospitals in 2018 was calculated as an indicator of neurosurgical training. Of 523,283 cases (male 55.3%) registered from 1360 participating institutions, the neurosurgical subgroup comprised of 33.9%. Among the major classifications, cerebrovascular diseases comprised the largest proportion overall and in the neurosurgical subgroup (53.1%, 41.0%, respectively), followed by neurotrauma (19.1%, 25.5%), and brain tumor (10.4%, 12.8%). Functional neurosurgery (6.4%, 3.7%), spinal and peripheral nerve disorders (5.1%, 10.1%), hydrocephalus/developmental anomalies (2.9%, 5.3%), and encephalitis/infection/inflammatory and miscellaneous diseases (2.9%, 1.6%) comprised smaller proportions. Most patients were aged 70-79 years in the overall cohort and neurosurgical subgroup (27.8%, 29.4%). Neurotrauma and cerebrovascular diseases in the neurosurgical subgroup comprised a higher and lower proportion, respectively, than in the overall cohort in elderly patients (e.g. 80 years, 46.9% vs. 33.5%, 26.8% vs. 54.4%). The 2018 median neurosurgical caseload per neurosurgeon in training was 80.7 (25-75th percentile 51.5-117.5). These initial results from 2018 reveal unique aspects of neurosurgical practice in Japan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2176/nmc.st.2019-0211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174247PMC
April 2020

MGMT Expression Contributes to Temozolomide Resistance in H3K27M-Mutant Diffuse Midline Gliomas.

Front Oncol 2019 21;9:1568. Epub 2020 Jan 21.

Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Japan.

Diffuse midline gliomas (DMGs) show resistance to many chemotherapeutic agents including temozolomide (TMZ). Histone gene mutations in DMGs trigger epigenetic changes including DNA hypomethylation, one of which is a frequent lack of O6-methyl-guanine-DNA methyltransferase () promoter methylation, resulting in increased MGMT expression. We established the NGT16 cell line with K27M and G328E gene mutations from a DMG patient and used this cell line and other DMG cell lines with gene mutation (SF7761, SF8628, JHH-DIPG1) to analyze promoter methylation, MGMT protein expression, and response to TMZ. Three out of 4 DMG cell lines (NGT16, SF8628, and JHH-DIPG1) had unmethylated promoter, increased MGMT expression, and showed resistance to TMZ treatment. SF7761 cells with gene mutation showed promoter methylation, lacked MGMT expression, and sensitivity to TMZ treatment. NGT16 line showed response to ALK2 inhibitor K02288 treatment . We confirmed that MGMT expression contributes to TMZ resistance in DMG cell lines. There is an urgent need to develop new strategies to treat TMZ-resistant DMGs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2019.01568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985080PMC
January 2020

Expression of the ghrelin/growth hormone secretagogue receptor axis and its functional role in promoting tumor growth in primary central nervous system lymphomas.

Neuropathology 2020 Jun 10;40(3):232-239. Epub 2020 Jan 10.

Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan.

Ghrelin and its receptor, growth hormone secretagogue receptor (GHS-R), have been found in a variety of malignant tumor tissues, suggesting a biological function of the ghrelin/GHS-R axis in tumor growth and progression. Among central nervous system tumors, primary central nervous system lymphomas (PCNSLs) are relatively rare and characterized by a rapid progression and poor prognosis. In order to clarify ghrelin expression and its functional role in promoting tumor growth and progression in PCNSLs, we undertook an immunohistochemical investigation for ghrelin and GHS-R expression in 43 patients and tested the effect of ghrelin inhibition on lymphoma cells. Furthermore, we investigated the expression of CD105, a marker for tumor angiogenesis, to explore its association with the ghrelin/GHS-R axis. The Kaplan-Meier method and Cox's proportional hazards regression model were used to determine the association of ghrelin/GHS-R expression with overall survival rate. The immunohistochemical study showed moderate/strong immunostaining of cells for ghrelin and GHS-R in 40 patients (93.0%) and 39 patients (90.7%), respectively. A ghrelin inhibitor did not affect tumor cell proliferation in vitro. Expression levels of ghrelin and GHS-R were divided into high and low groups by the rate of moderate-strong staining cells to tumor cells. The survival rate was significantly lower in patients with high GHS-R expression (P = 0.0368 by log-rank test; P = 0.0219 by Wilcoxon test). In addition, multivariate analysis of overall survival using Cox's proportional hazards regression model indicated that GHS-R was a significant independent prognostic factor (P = 0.0426). CD105 expression on tumor vessels was positive in 33 patients (33/37, 89.2%). There was a positive correlation between the moderate-strong staining rate of ghrelin and CD105-positive vessel count. These results indicated that the ghrelin/GHS-R axis plays a potential role in promoting tumor growth and progression through neoangiogenesis, rather than the proliferation of tumor cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/neup.12634DOI Listing
June 2020

Vascular Hyperintensity on Fluid-Attenuated Inversion Recovery Indicates the Severity of Hypoperfusion in Acute Stroke.

J Stroke Cerebrovasc Dis 2020 Feb 22;29(2):104467. Epub 2019 Nov 22.

Department of Neurosurgery, Brain Research Institute, University of Niigata, Chuo-ku, Niigata, Japan. Electronic address:

Background And Aim: Although fluid-attenuated inversion recovery vascular hyperintensities may be frequently seen in acute large-artery ischemic stroke, reports on their prognostic utility had been conflicting due to lack of quantitative evaluation of the perfusion status based on the signal intensity. We hypothesized that greater hyperintensity represents more severe hypoperfusion.

Methods: Overall, 27 patients with acute occlusion of the proximal middle cerebral artery were divided into 2 groups, based on their signal intensity in the insular segment of middle cerebral artery on the affected side, relative to that of the insular cortex: the low signal intensity group (hypo- or isointense signals, n = 12) and the high signal intensity group (hyperintense signals, n = 15). Using dynamic susceptibility contrast magnetic resonance imaging, we assessed the time of the maximum value of the residue function and mean transit time, in the entire middle cerebral artery cortical area and diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score regions, including the corona radiata.

Results: The high signal intensity group had significantly longer time of the maximum value of the residue function in all the diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score regions, except the M3 and M6 regions, and significantly longer mean transit time in the M1 and M4 regions.

Conclusions: Quantitative analysis of the perfusion parameters revealed more severely compromised and widely disturbed perfusion status in the high signal intensity group than in the low signal intensity group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2019.104467DOI Listing
February 2020

Pineal Region Germinoma in the Seventh Decade of Life: A Case Report.

NMC Case Rep J 2019 Aug 11;6(3):75-78. Epub 2019 Jun 11.

Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Niigata, Japan.

Germ cell tumors typically occur in children and adolescents. We here report a rare case of pineal region germinoma in the seventh decade of life. A 62-year-old man presented with double vision. Computerized tomography and magnetic resonance imaging (MRI) identified a heterogeneously enhanced tumor with calcification in the pineal region with ventricular dilatation due to aqueduct stenosis. The tumor had not been observed at all on MRI obtained 2 years previously. The patient underwent endoscopic biopsy and third ventriculostomy for the obstructive hydrocephalus. The tumor was histopathologically diagnosed as a pure germinoma. The patient underwent radiomonotherapy, resulting in his complete remission, which was confirmed by a series of follow-up MRI studies and hematological examinations. Intracranial germinoma should be considered in the differential diagnosis of pineal region tumors regardless of age, even though the tumor was undetectable on the previous neuroimaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2176/nmccrj.cr.2018-0221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692596PMC
August 2019

Dramatic response of BRAF V600E-mutant epithelioid glioblastoma to combination therapy with BRAF and MEK inhibitor: establishment and xenograft of a cell line to predict clinical efficacy.

Acta Neuropathol Commun 2019 07 25;7(1):119. Epub 2019 Jul 25.

From the Departments of Neurosurgery, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata, Japan.

Epithelioid glioblastoma is a rare aggressive variant of glioblastoma (GBM) characterized by a dismal prognosis of about 6 months and frequent leptomeningeal dissemination. A recent study has revealed that 50% of epithelioid GBMs harbor three genetic alterations - BRAF V600E mutation, TERT promoter mutations, and homozygous deletions of CDKN2A/2B. Emerging evidence support the effectiveness of targeted therapies for brain tumors with BRAF V600E mutation. Here we describe a dramatic radiographical response to combined therapy with BRAF and MEK inhibitors in a patient with epithelioid GBM harboring BRAF V600E mutation, characterized by thick spinal dissemination. From relapsed tumor procured at autopsy, we established a cell line retaining the BRAF V600E mutation, TERT promoter mutation and CDKN2A/2B loss. Intracranial implantation of these cells into mice resulted in tumors closely resembling the original, characterized by epithelioid tumor cells and dissemination, and invasion into the perivascular spaces. We then confirmed the efficacy of treatment with BRAF and MEK inhibitor both in vitro and in vivo. Epithelioid GBM with BRAF V600E mutation can be considered a good treatment indication for precision medicine, and this patient-derived cell line should be useful for prediction of the tumor response and clarification of its biological characteristics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40478-019-0774-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659204PMC
July 2019

Comparison of circulating tumor DNA between body fluids in patients with primary central nervous system lymphoma.

Leuk Lymphoma 2019 12 15;60(14):3587-3589. Epub 2019 Jul 15.

Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428194.2019.1639169DOI Listing
December 2019

Treatment Strategies for Infectious Intracranial Aneurysms: Report of Three Cases and Review of the Literature.

Neurol Med Chir (Tokyo) 2019 Sep 4;59(9):344-350. Epub 2019 Jul 4.

Department of Neurosurgery, Brain Research Institute, Niigata University.

We retrospectively reviewed the cases of three patients with infectious intracranial aneurysms (IIAs), and discuss the indications for surgical and endovascular treatments. We treated two men and one woman with a total of six aneurysms. The mean age was 43.3 years, ranging from 36 to 51 years. One patient presented initially with an intraparenchymal hemorrhage, one with mass effect, and the other one had four aneurysms (one causing subarachnoid hemorrhages and the other causing delayed intraparenchymal hemorrhages). The average size of all aneurysms was 12.2 mm (range, 2-50 mm). They were preferentially located in the distal posterior cerebral artery, and then, in the middle cerebral artery. All cases were caused by infective endocarditis. We selected endovascular treatments for five aneurysms and treated all but one within 24 h from detection. One aneurysm was treated by combined therapy with endovascular intervention and surgery. After treatment, none of the IIAs presented angiographical recurrence or re-bleeding. If feasible, endovascular treatment is probably the first choice, but a combined surgical and endovascular approach should be considered if surgery or endovascular treatment alone are not feasible. The method of treatment should be individualized. For cases with high risk of aneurysm rupture, treatment should be performed as soon as possible.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2176/nmc.oa.2019-0051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753255PMC
September 2019

Prosthesis Used in Microvascular Decompressions: A Multicenter Survey in Japan Focusing on Adverse Events.

World Neurosurg 2019 Oct 14;130:e251-e258. Epub 2019 Jun 14.

Fujita Health University School of Medicine, Toyoake, Japan.

Objective: To investigate the characteristics of materials used as prostheses for microvascular decompression surgery (MVDs) in Japan and their possible adverse events (AEs) to determine preferable materials for MVDs.

Methods: A questionnaire was sent to all members of the Japanese Society for MVDs, and answers were obtained from 59 institutions.

Results: Among a total of 2789 MVDs, 1088 operations for trigeminal neuralgia, 1670 for hemifacial spasm, and 31 others, including 117 reoperations, were performed between April 2011 and March 2014. Nonabsorbable material was used in 96.5% of MVDs, including polytetrafluoroethylene (PTFE) (80.5%), polyurethane (11.9%), expanded PTFE (2.1%), and silk thread (1.47%). The use of absorbable materials, including fibrin glue (87.5%), cellulose (13.5%), gelatin (4,77%), and collagen (1.76%), was reported. The major combinations were PTFE with fibrin glue (58.7%) followed by PTFE alone (7.60%). Eighty-eight AEs in 85 (3.2%) cases were reported among 2672 first operations. AEs included 51 central nervous system dysfunctions, 15 wound infections/dehiscence, and 10 others, which were presumed to be related to the intraoperative procedure. Among relatively high-, moderate-, and low-volume centers, there were no significant differences in the frequency of AEs (P = 0.077). Tissue-prosthesis adhesion and/or granuloma formation were reported in 13 cases of 117 reoperations. The incidence of adhesion-related recurrence was 11.1% of all reoperations.

Conclusions: The number of AEs was quite low in this survey, and intradural use of any prosthesis reported in this paper might be justified; however, further development of easily handled and less-adhesive prosthesis materials is awaited.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2019.06.053DOI Listing
October 2019

Podoplanin Expression and IDH-Wildtype Status Predict Venous Thromboembolism in Patients with High-Grade Gliomas in the Early Postoperative Period.

World Neurosurg 2019 Aug 15;128:e982-e988. Epub 2019 May 15.

Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata.

Objective: Venous thromboembolism (VTE) often is encountered in patients with high-grade gliomas. The underlying mechanisms are unclear, as is the optimal prophylactic protocol. The purpose of the present study was to identify risk factors of VTE and examine the validity of early VTE detection in high-grade gliomas.

Methods: We reviewed the medical records of 165 patients with newly diagnosed high-grade glioma treated at Niigata University Hospital during the years 2009 to 2016. If the serum D-dimer levels increased to 5.0 μg/mL or more, computed tomography was performed to detect VTE. Furthermore, immunohistochemistry with antibodies against podoplanin was performed on available 101 tumor tissues.

Results: Of the 165 patients, 44 (26.7%) developed VTE. Of the 44 patients, 34 (79.5%) developed VTE within 7 days after surgery. No fatal VTE occurred and major complications secondary to anticoagulation occurred in only 2 (1.2%) patients. On multivariate analysis, lower Karnofsky Performance Scale status, podoplanin expression, and isocitrate dehydrogenase-wildtype status were independently associated with the risk of VTE (P < 0.05).

Conclusions: We found that most VTEs occurred early in the postoperative period and commonly in patients with lower Karnofsky Performance Scale status and isocitrate dehydrogenase-wildtype gliomas, which expressed podoplanin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2019.05.049DOI Listing
August 2019

Malignant Hyperthermia and Cerebral Venous Sinus Thrombosis After Ventriculoperitoneal Shunt in Infant with Schizencephaly and COL4A1 Mutation.

World Neurosurg 2019 Jul 25;127:446-450. Epub 2019 Apr 25.

Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Japan.

Background: Schizencephaly is a rare congenital central nervous system malformation characterized by linear, thickened clefts of the cerebral mantle. Recently, germline mutations in collagen type IV alpha 1 (COL4A1) have been reported to be a genetic cause of schizencephaly as a result of prenatal stroke. Patients with COL4A1 mutation demonstrate a variety of disease phenotypes. However, little is known about the potential complications of patients with COL4A1 mutations before and after neurologic surgery.

Case Description: A 9-month-old boy with schizencephaly and a congenital cataract underwent a ventriculoperitoneal shunt for progressive hydrocephalus. Postoperatively, he developed malignant hyperthermia and cerebral venous thrombosis. Early treatment with dantrolene sodium and hydration was effective. Genetic testing revealed a germline COL4A1 mutation.

Conclusions: To our knowledge, malignant hyperthermia and cerebral venous thrombosis have not been reported in the literature in patients with COL4A1 mutations after surgery. Schizencephaly arising from COL4A1 mutations might be a disease prone to these adverse effects because this mutation is known to be associated with venous tortuosity, venous vulnerability, and muscle spasms due to basement membrane protein abnormalities. We need to better understand the wide spectrum of clinical phenotypes of COL4A1 mutations and potential complications in order to better manage surgery of patients with schizencephaly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2019.04.156DOI Listing
July 2019

Noninvasive Vagus Nerve Stimulation Prevents Ruptures and Improves Outcomes in a Model of Intracranial Aneurysm in Mice.

Stroke 2019 05;50(5):1216-1223

From the Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown (T.S., T.T., T.Q., C.A.).

Background and Purpose- Inflammation is a critical determinant of aneurysmal wall destabilization, growth, and rupture risk. Targeting inflammation may suppress aneurysm rupture. Vagus nerve stimulation (VNS) has been shown to suppress inflammation both systemically and in the central nervous system. Therefore, we tested the effect of a novel noninvasive transcutaneous VNS approach on aneurysm rupture and outcome in a mouse model of intracranial aneurysm formation with wall inflammation. Methods- Aneurysms were induced by a single stereotaxic injection of elastase into the cerebrospinal fluid at the skull base, combined with systemic deoxycorticosterone-salt hypertension, without or with high-salt diet, for mild or severe outcomes, respectively. Cervical VNS (two 2-minute stimulations 5 minutes apart) was delivered once a day starting from the day after elastase injection for the duration of follow-up. Transcutaneous stimulation of the femoral nerve (FNS) served as control. Multiple aneurysms developed in the circle of Willis and its major branches, resulting in spontaneous ruptures and subarachnoid hemorrhage, neurological deficits, and mortality. Results- In the milder model, VNS significantly reduced aneurysm rupture rate compared with FNS (29% versus 80%, respectively). Subarachnoid hemorrhage grades were also lower in the VNS group. In the more severe model, both VNS and FNS arms developed very high rupture rates (77% and 85%, respectively). However, VNS significantly improved the survival rate compared with FNS after rupture (median survival 13 versus 6 days, respectively), without diminishing the subarachnoid hemorrhage grades. Chronic daily VNS reduced MMP-9 (matrix metalloproteinase-9) expression compared with FNS, providing a potential mechanism of action. As an important control, chronic daily VNS did not alter systemic arterial blood pressure compared with FNS. Conclusions- VNS can reduce aneurysm rupture rates and improve the outcome from ruptured aneurysms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.118.023928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476688PMC
May 2019