Yoshimasa Niiya

Susceptibility of brain microvascular endothelial cells to advanced glycation end products-induced tissue factor upregulation is associated with intracellular reactive oxygen species

There is accumulating evidence that advanced glycation end products (AGEs) are relevant to the formation of vascular complications in diabetes mellitus. The aim of this study was to investigate whether AGEs have a significant effect on tissue factor (TF) expression in brain microvascular endothelial cells compared with that in other arterial endothelial cells. Cultured bovine brain microvascular endothelial cells (BBMECs) and aortic endothelial cells (BAECs) were incubated in medium containing glyceraldehyde-derived AGE (glycer-AGE). TF mRNA expression, protein expression, and activity were measured at multiple time points after glycer-AGE incubation. Participation of reactive oxygen species (ROS) in the effect of glycer-AGE on TF expression was investigated by treatment with a free radical scavenger, edaravone, and intracellular ROS measurements with dihydroethidium (DHE). Basic TF mRNA expression was greater in BBMECs than in BAECs. Glycer-AGE significantly upregulated TF mRNA expression in both cells, and the upregulation was more prominent in BBMECs than in BAECs. TF protein expression and activity were also upregulated with a pattern of being greater in BBMECs than in BAECs. Edaravone significantly attenuated the AGE-induced upregulation of TF mRNA expression, protein expression, and activity. Intracellular ROS levels measured with DHE-stained fluorescent intensity were significantly upregulated by glycer-AGE with a pattern of being greater in BBMECs than in BAECs. AGE-induced ROS upregulation was attenuated by edaravone like AGE-induced TF upregulation. These results suggest that brain microvascular endothelial cells are more susceptible to AGE-induced TF upregulation than aortic endothelial cells, and that this susceptibility is associated with levels of intracellular ROS.

Advanced Glycation End Products Increase Permeability of Brain Microvascular Endothelial Cells through Reactive Oxygen Species–Induced Vascular Endothelial Growth Factor Expression

BACKGROUND Advanced glycation end products (AGEs) have been implicated as important factors in the pathogenesis of diabetic vascular complication. The aim of this study is to reveal the effect of AGEs on permeability of brain microvascular endothelial cells (BMECs) in order to assess its role in diabetic vascular complications. METHODS Permeability was determined by the flux of fluorescein isothiocyanate (FITC)-labeled dextran (4-kDa molecular weight) through endothelial cell monolayers on a transwell system and was compared between bovine BMECs (BBMECs) and bovine aortic endothelial cells (BAECs). The effect of AGEs on permeability was investigated in terms of the role of vascular endothelial growth factor (VEGF) and reactive oxygen species (ROS). RESULTS Permeability and VEGF expression were significantly increased by the addition of 100 μg/mL of glycer-AGEs in BBMECs. They also tended to be increased in BAECs, but not enough to make a significant difference. Simultaneous treatment with an anti-VEGF antibody suppressed the AGE-enhanced permeability. Furthermore, simultaneous treatment with a free radical scavenger, edaravone, also suppressed the AGE-enhanced permeability and the increase in VEGF mRNA levels and AGE-induced intracellular ROS overproduction. CONCLUSIONS These results suggest that BMECs are more susceptible than aortic endothelial cells to AGE-enhanced permeability and that AGE-enhanced permeability is dependent on VEGF expression induced by ROS over production.

Characteristics of Symptomatic Intracerebral Hemorrhage in Patient Receiving Direct Oral Anticoagulants: Comparison with Warfarin

BACKGROUND Direct oral coagulants (DOAC) have been shown to decrease the frequency of intracerebral hemorrhage (ICH) compared with warfarin. However, the precise characteristics, such as the size and locations of the hemorrhage, and outcome and onset time of ICH in patient taking DOAC are not fully elucidated. METHODS We retrospectively analyzed the characteristics of symptomatic patients with ICH taking either DOAC or warfarin between January 2012 and December 2015. RESULTS Out of 400 consecutive patients with ICH, 15 patients were DOAC-ICH and 24 patients were warfarin-ICH. DOAC-ICH was observed in 6 patients with 10 mg of rivaroxaban, 5 patients with 15 mg of rivaroxaban, and 1 patient with 10 mg of apixaban, 5 mg of apixaban, 30 mg of edoxaban, and 60 mg of edoxaban. Prothrombin time was well controlled in most of the warfarin-ICH patients (83.3%). The locations of ICH were similar in both groups; however, median ICH volume was significantly smaller in DOAC-ICH patients than in warfarin-ICH patients (P < .01) and ICH around basal ganglia seemed to show great difference between the groups. DOAC-ICH patients showed better neurological outcome at the time of discharge than warfarin patients (P < .01), and the ratio of good prognosis was significantly higher in the DOAC-ICH patients than in the warfarin-ICH patients (P < .01). The onset of warfarin-ICH was frequently observed in the morning and evening, whereas DOAC-ICH did not show any specific onset time. CONCLUSIONS Patients with DOAC-ICH showed smaller ICH volume and better clinical outcomes than patients with warfarin-ICH, and DOAC-ICH did not show any specific onset peak.

A case of midbrain infarction with acute bilateral cerebellar ataxia visualized by diffusion tensor imaging.

An 85-year-old woman with hypertension was admitted with a sudden onset of gait disturbance and dysarthria. On admission, the patient showed severe bilateral cerebellar ataxia with moderate right medial longitudinal fasciculus (MLF) syndrome. Magnetic resonance (MR) imaging showed an acute infarction in the lower and medial part of midbrain. Diffusion tensor imaging (DTI) started from both cerebellar peduncles revealed that the lesion of the acute infarction matched the decussation of superior cerebellar peduncle where crossing of tract was seen and a part of its tract was interrupted at the site. Interruption of the cerebellum red nuclear path at the medial part of midbrain was considered to be the reason for bilateral cerebellar ataxia and visualization of cerebellum red nuclear path by DTI can give better understanding of the neurological symptom.

Irregular Neointimal Lining with Prominent Proliferative Activity After Carotid Patch Angioplasty: An Autopsy Case Report

OBJECTIVE Although the healing response after carotid balloon injury and carotid patch angioplasty injury has been well-documented in animal models, there is limited information about this process after carotid endarterectomy (CEA) in human patients. CASE DESCRIPTION We describe the autopsy results of a 79-year-old man who died 18 days after CEA with patch angioplasty. The treated carotid artery had an adequate luminal diameter. Elastica-Masson staining revealed that the treated portion was covered with neointima but the patch graft was exposed to the arterial lumen at 18 days after CEA. Immunohistochemistry staining for alpha-smooth muscle actin (α-SMA), von-Willebrand factor, and vascular endothelial growth factor receptor-2 revealed that the neointima was mainly composed of α-SMA-positive cells. In addition, the α-SMA-rich neointima had many more Ki-67-positive cells than did the internal carotid artery intima in the area beyond the CEA-treated portion. CONCLUSIONS This case report is the first to describe an entire carotid artery specimen in the acute stage after CEA with patch angioplasty. These findings suggest that an α-SMA-rich neointima with prominent proliferative activity covers the inner surface of the treated carotid artery, but patch grafts are left uncovered. The intrinsic arterial wall may have an important role in intimal regeneration after CEA, although the nature of the neointima and the mechanism by which it regulates proliferative activity remain unclarified.

Mollaret Meningitis with High Level of Cytokines in CSF Successfully Treated by Indomethacin

A rare case of Mollaret meningitis characterized by four recurrent episodes of aseptic meningitis during the 3-year periods were reported. The patient showed high fever and severe headache accompanied by high level of cerebrospinal fluid (CSF) cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alfa (TNF-a). The symptoms and high CSF cytokines were dramatically resolved immediately after inducing indomethacin treatment. Reactivation of the latent virus is considered to be the cause of this rare disease and indomethacin is estimated to inhibit periodic abnormal generation of eicosanoid in the brain resulting in reducing fever and subsequent inflammation.

Serial Arterial Spin Labeling May Be Useful in Assessing the Therapeutic Course of Cerebral Venous Thrombosis : Case Reports

We report two cases of cerebral venous thrombosis (CVT) which serial arterial spin labeling (ASL) was useful in evaluating the clinical course of the disease. A 48-year-old female presented with acute seizure, and was diagnosed as transverse-sigmoid sinus thrombosis. ASL imaging revealed low signal intensity in the right temporal lobe, suggesting the decreased perfusion by elevated venous pressure. Soon after the treatment, while the development of venous collateral has not fully observed by magnetic resonance (MR) angiography, low ASL signal within the right temporal lobe have shown remarkable improvement. A 65-year-old female presented with vomiting and subsequent seizure was diagnosed as superior sagittal sinus thrombosis. The low ASL signal within the right frontal lobe seen in the acute stage improved to the normal level by the course of time, before the good collateral can be seen by MR angiography. This is the first report to assess the sequential change of the cerebral perfusion of CVT by ASL, and ASL may provide additional useful information in combination with conventional modalities.

Double Crush of L5 Spinal Nerve Root due to L4/5 Lateral Recess Stenosis and Bony Spur Formation of Lumbosacral Transitional Vertebra Pseudoarticulation: A Case Report and Review

We present a case of double-crushed L5 nerve root symptoms caused by inside and outside of the spinal canal with spur formation of the lumbosacral transitional vertebra (LSTV). A 78-year-old man presented with 7-year history of moderate paresis of his toe and left leg pain when walking. Magnetic resonance imaging (MRI) revealed spinal stenosis at the L3/4 and 4/5 spinal levels and he underwent wide fenestration of both levels. Leg pain disappeared and 6-min walk distance (6MWD) improved after surgery, however, the numbness in his toes increased and 6MWD decreased 9 months after surgery. Repeated MR and 3D multiplanar reconstructed computed tomography (CT) images showed extraforaminal impingement of the L5 root by bony spur of the left LSTV. He underwent second decompression surgery of the L5/S via the left sided Wiltse approach, resulting in the improvement of his symptoms. The impingement of L5 spinal nerve root between the transverse process of the fifth lumbar vertebra and the sacral ala is a rare entity of the pathology called “far-out syndrome (FOS)”. Especially, the bony spur formation secondary to the anomalous articulation of the LSTV (LSPA) has not been reported. These articulations could be due to severe disc degeneration, following closer distance and contact between the transverse process and the sacral ala. To our knowledge, this is the first report describing a case with this pathology and may be considered in cases of failed back surgery syndromes (FBSS) of the L5 root symptoms.

Lateral Position of the External Carotid Artery: A Rare Variation to Be Recognized During Carotid Endarterectomy

BACKGROUND External carotid artery (ECA) positioned laterally to the internal carotid artery (ICA) at the level of the common carotid artery (CCA) bifurcation is occasionally encountered during carotid endarterectomy (CEA). This study aimed to determine the frequency of this phenomenon and provide technical tips for performing CEA. METHODS The study included 199 consecutive patients (209 carotid arteries) who underwent CEA at Otaru Municipal Medical Center in 2007-2014. The position of the ECA with respect to the ICA at the CCA bifurcation was preoperatively rated as either lateral or normal, using three-dimensional computerized tomographic angiography (3-D CTA) anteroposterior projections. Postoperative diffusion-weighted images (DWIs), and postoperative 3-D CTA images were reviewed. RESULTS Among the 209 carotid arteries with atherosclerosis, 11 instances (5.3 %) of lateral position of the ECA were detected in 11 patients. Ten of these arteries (91 %) were right-sided (odds ratio 11.1; 95 % confidence interval 1.38-88.9). Wider longitudinal exposure of the arteries was used during CEA, and the CCA and ECA were rotated clockwise or counter clockwise. The ICA lying behind the ECA along the surgical access route was then pulled out laterally and moved to the shallow surgical field. Cross-clamping, arteriotomy, plaque removal, and wall suturing were performed as usual. No cerebral infarcts were detected on postoperative DWIs, and 3-D CTA revealed no CCA and ICA kinking. CONCLUSIONS Lateral position of the ECA is not extremely rare in patients undergoing CEA for atherosclerosis and may be a congenital variation, although this is still controversial. CEA can be performed safely if the arteries from the CCA to the ICA are rotated, and the ICA is moved to the shallow surgical field under wider longitudinal exposure. Although no postoperative cerebral infarcts were detected, the risk of artery-to-artery embolism resulting from artery repositioning prior to plaque removal should be taken into consideration.

[Radiotherapy for Alleviation of Paraparesis due to Leptomeningeal and Cauda Equina Metastasis of HER2-Positive Breast Cancer: A Case Report].

Leptomeningeal metastasis is a rare entity and its diagnosis is often difficult. Moreover, evidence-based therapeutic strategies have not yet been established. A 52-year-old woman presented with high fever and was diagnosed with bacterial meningitis at first examination;although her fever was alleviated, she experienced motor weakness in both of her lower extremities. Ga scintigraphy highlighted the hot-spot areas of the disease in the cranial bone. She was then transferred to our department. Open biopsy of the skull showed metastasis of the cancer. Chest CT results indicated right breast cancer and Gd-DTPA imaging showed obvious enhancement of the pia mater around the conus medullaris and cauda equina. However, cerebrospinal fluid(CSF)cytological examination did not show the presence of any positive cells;consequently, mastectomy was performed in the thoracic surgical department. The severity of paraparesis and pain in her legs increased;however, repeat MRI 1 month later showed no evidence of any change. Therefore, we performed biopsy of the cauda equina and arachnoid lesions. The pathological diagnosis was metastasis of breast cancer with positive human epidermal growth factor receptor 2(HER2)immunological staining. The results of a repeat cytological examination of the CSF during the surgery were negative. Local radiotherapy(25 Gy/5 Fr)as a monotherapy was selected for the patient, because her family did not approve of the combination of radiotherapy and chemotherapy. The severity of both paraparesis and limb pain decreased immediately after the radiotherapy.