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Hideyuki Ishihara

Publications and source records attributed to Hideyuki Ishihara.

10 recordsLinked to original sources
PubMed2006

Cilostazol inhibits the redistribution of the actin cytoskeleton and junctional proteins on the blood-brain barrier under hypoxia/reoxygenation.

Cilostazol is a selective inhibitor of cyclic nucleotide phosphodiesterase 3 (PDE3), which induces a vasodilatoric antiplatelet effect. In the present study, we investigated the impact of cilostazol on the blood-brain barrier (BBB), while focusing on the actin cytoskeleton (F-actin), the permeability of endothelial cells, and the junctional proteins under hypoxia/reoxygenation (H/R). Cilostazol was thus found to inhibit the cytoskeletal reorganization under H/R, in which F-actin decrease at the cell periphery. Accordingly, cilostazol was able to attenuate the hyperpermeability of endothelial cells in H/R to the level of the permeability in normoxia. However, the adherens junction (AJ) protein VE-cadherin was not preserved in the presence of cilostazol under H/R. On the other hand, beta-catenin was slightly retained by cilostazol. In contrast to the redistribution of these proteins, immunoblotting demonstrated the total amount of AJ and tight junction (TJ) proteins (occludin, ZO-1 and ZO-2) to not show any significant change under H/R stress in either the presence or absence of cilostazol. Taken together, cilostazol potently displayed a protective effect against acute ischemia by preventing an increase in the endothelial permeability through the preservation of the actin cytoskeleton and the redistribution of junctional proteins.

Actins↗
PubMed2005

Distribution and functional activity of P-glycoprotein and multidrug resistance-associated proteins in human brain microvascular endothelial cells in hippocampal sclerosis.

Multidrug resistance protein, also referred as P-glycoprotein (P-gp, MDR1; ABCB1) and multidrug resistance-associated protein (MRP) 1 (ABCC1) and 2 (ABCC2) are, thus far, candidates to cause antiepileptic drug (AED) resistance epilepsy. In this study, we investigated P-gp, MRP1 and MRP2 expression, localization and functional activity on cryosections and isolated human brain-derived microvascular endothelial cells (HBMEC) from epileptic patients (HBMEC-EPI) with hippocampal sclerosis (HS), as compared with HBMEC isolated from normal brain cortex (HBMEC-CTR). We examined the expression and distribution of three transporters, P-gp, MRP1 and MRP2 on two major parts of the resected tissue, the hippocampus and the parahippocampal gyrus (Gph). P-gp showed diffuse expression not only in endothelium but also by parenchymal cells in both the hippocampus and the Gph. MRP1 labeling was observed in parenchymal cells in the Gph. By contrast, MRP2 was mainly found in endothelium of the hippocampus. P-gp and MRP1 expression in the Gph was relatively high in the patient with long-term seizure history. Quantitative RT-PCR analysis of HBMEC revealed that MDR1, MRP1 as well as MRP5 (ABCC5) and MRP6 (ABCC6) were overexpressed in HBMEC-EPI at the mRNA level. HBMEC from both normal and epilepsy groups displayed protein expression of P-gp, whereas MRP1 and MRP2 were seen only in HBMEC-EPI. Accordingly, it is of particular interest that MRP functional activities were observed in HBMEC-EPI, but not in HBMEC-CTR. Our results suggest that complex MDR expression changes not only in the hippocampus but in the Gph may play a role in AED pharmacoresistance in intractable epilepsy patients with mesial temporal lobe epilepsy (MTLE) by altering the permeability of AEDs across the blood-brain barrier (BBB).

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Association of intra- and extradural developmental venous anomalies, so-called venous angioma and sinus pericranii.

INTRODUCTION: We report a case of cerebellar venous angioma and parietal sinus pericranii. DISCUSSION: Venous angioma is classified as a developmental venous anomaly (DVA) because it is not a neoplasm but a variant that develops during embryogenesis. Sinus pericranii should be classified as extradural-type DVA. Although there have been few reports of association between these conditions, both are suspected to have the same pathogenesis, i.e., transient venous hypertension in the late embryonic period influencing venous development.

Central Nervous System Venous Angioma↗
PubMed2005

Induction of reactive oxygen intermediates-dependent programmed cell death in human malignant ex vivo glioma cells and inhibition of the vascular endothelial growth factor production by taurolidine.

OBJECT: Taurolidine, a derivative of the amino acid taurin, was recently found to display a potent antineoplastic effect both in vitro and in vivo. The authors therefore initiated studies to assess the potential antineoplastic activity of taurolidine in human glioma cell lines and in ex vivo malignant cell cultures. They also studied the mechanisms that induce cell death and the impact of taurolidine on tumor-derived vascular endothelial growth factor (VEGF) production. METHODS: Cytotoxicity and clonogenic assays were performed using crystal violet staining. In the cytotoxicity assay 100% of glioma cell lines (eight of eight) and 74% of ex vivo glioma cultures (14 of 19) demonstrated sensitivity to taurolidine, with a mean median effective concentration (EC50) of 51 +/- 28 microg/ml and 56 +/- 23 microg/ml, respectively. Colony formation was inhibited by taurolidine, with a mean EC50 of 7 +/- 3 microg/ml for the cell lines and a mean EC50 of 3.5 +/- 1.7 microg/ml for the ex vivo glioma cultures. On observing this high activity of taurolidine in both assays, the authors decided to evaluate its cell death mechanisms. Fragmentation of DNA, externalization of phosphatidylserine, activation of poly(adenosine diphosphate-ribose) polymerase, loss of the mitochondrial membrane potential followed by a release of apoptosis-inducing factor, and typical apoptotic features were found after taurolidine treatment. Cell death was preceded by the generation of reactive O2 intermediates, which was abrogated by N-acetylcysteine but not by benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. Moreover, taurolidine also induced suppression of VEGF production on the protein and messenger RNA level, as shown by an enzyme-linked immunosorbent assay and by reverse transcription-polymerase chain reaction. CONCLUSIONS: Given all these findings, taurolidine may be a promising new agent in the treatment of malignant gliomas; it displays a combination of antineoplastic and antiangiogenic activities, inducing tumor cell apoptosis and inhibiting tumor-derived VEGF production.

Acetylcysteine↗
PubMed2004

Increased matrix metalloproteinase-9 in blood in association with activation of interleukin-6 after traumatic brain injury: influence of hypothermic therapy.

Recent experimental data have shown that levels of matrix metalloproteinase-9 (MMP-9) increase after traumatic brain injury (TBI), degrading components of the basal lamina disrupting the blood-brain barrier. However, the post-traumatic secretion patterns of MMP-9 in humans are unknown. We measured the concentration of MMP-9 in plasma after TBI at the same time as the concentration of interleukin-6 (IL-6) in serum. Levels of MMP-9 and IL-6 in systemic arterial and jugular venous blood from seven patients with TBI were measured on days 0 and 1 post-injury. All patients underwent hypothermia at 32-35 degrees C as soon as possible after admission. Before induction of hypothermia, levels of MMP-9 in arterial and internal jugular venous blood exceeded the normal range. Higher MMP-9 levels were detected in internal jugular venous blood than in arterial blood. After hypothermia had been induced, MMP-9 levels in arterial blood and internal jugular venous blood decreased significantly, to within the normal range. In addition to these changes, a significant correlation was seen between levels of MMP-9 and IL-6 in internal jugular venous blood during the investigation period. These results indicate that MMP-9 is elevated in patients with acute TBI, and may play an important role in traumatic brain damage. The elevation of MMP-9 is associated with inflammatory events following TBI. Hypothermic intervention may suppress the elevation of MMP-9 with suppression of the inflammatory response, affording neuroprotection in TBI.

Adolescent↗
PubMed2004

[A case of intractable epilepsy presenting epileptic spasm treated with callosotomy in childhood].

We present a case of intractable epilepsy presenting epileptic spasm successfully treated with anterior callosotomy in childhood. A 12-year-old boy had seizures frequently since the age of 11 months which were diagnosed as an infantile spasm. He underwent various treatments including ACTH therapy, but the seizures were intractable. Characteristics of his seizures were an abrupt axial movement leading to sustained posturing, most often truncal, and neck flexion with pronounced arm extension and abduction. He lost consciousness transiently and these seizures frequently occurred in clusters and the duration of seizure was 1 to 3 seconds. Neurologically he had no deficit, but his intelligence was below the standard level. Magnetic resonance image (MRI) showed no abnormalities in the brain. Electroencephalogram (EEG) demonstrated secondary bilateral synchrony (SBS) with left frontal dominance in amplitude. Subdural strip electrodes were implanted bilaterally over the frontal lobes to detect an epileptogenic region. However intracranial ictal-EEG demonstrated an abrupt bilateral desynchronization for 1-3 seconds. As the epileptogenic zone was not clearly identified and an abrupt bilateral desynchronization was identified, anterior callosotomy was performed. Since surgery, he has remained seizure-free for two years while taking anticonvulsants and the SBS has disappeared. This case may indicate that the corpus callosum influences the occurrence of epileptic spasm and SBS on EEG.

Child↗
PubMed2004

[Consensus and controversy in the treatment of ischemic cerebrovascular diseases].

Surgical and endovascular revascularization for ischemic cerebrovascular diseases (CVD) should be strictly indicated based on medical treatment. In this report, we describe current consensus and controversy in the treatment of ischemic CVD, and perspectives. 1) Local intra-arterial fibrinolytic therapy for acute cerebral embolism; intra-venous t-PA can be beneficial when given within 3 hours of stroke onset (NINDS), but many patients present later after stroke onset and alternative treatments are needed. Despite an increased frequency intracranial hemorrhage, treatment with intra-arterial proUK within 6 hours for MCA occlusion significantly improved clinical outcome at 90 days (mRS 40% >25%, PROACT-II). MELT-Japan are going now and waiting for results. 2) Carotid stenting; Carotid angioplasty and stenting (CAS) has been proposed as an alternative to carotid endarterectomy (CEA) in those considered at high risk for CEA. SAPPHIRE study confirmed CAS is an excellent option for patients with coexisting coronary artery disease, congestive heart failure, and other comorbid conditions that make them poor candidates for CEA. Now, CREST in USA and CSSA in Europe are going for randomized trial compared with CEA and CAS in any risk for CEA patients. 3) Stenting for intracranial arteries; Stroke rates in patients with symptomatic intracranial stenosis may be high on medical therapy. Although there is no clinical evidence and appropriate devices for intracranial vessels, it seems to be a potentially effective in the future.

Brain Ischemia↗
PubMed2002

Evaluation of brain toxicity following near infrared light exposure after indocyanine green dye injection.

Indocyanine green (ICG) has excellent safety records and is widely used in medical diagnosis. Recently, a new method has been developed to estimate cerebral blood flow (CBF) using ICG in combination with near-infrared spectroscopy (NIRS). The new technique may be of wide clinical interest, as it is noninvasive and easy to perform at the bedside in stroke patients. Additionally, ICG with the use of specific wavelength lasers is documented to be effective in photodynamic therapy (PDT). Under normal conditions ICG does not cross the intact blood brain barrier (BBB). However, in patients with brain injuries where the BBB may be disturbed, ICG could accumulate in brain parenchyma and in combination with NIR-light exposure, phototoxicity could occur. The aim of the present study was to examine the possible toxicity of ICG in combination with NIRS in a specific setting for CBF measurements. In five rats with mannitol induced BBB breakdown no traces of ICG were found during spectrophotometric analysis of the brain cell suspensions. In ten rats with disrupted BBB there were no significant increases of brain temperature or histological signs of brain damage following 1 h NIR-light exposure after ICG injection. The existing literature concerning the application of ICG in combination with NIR light is reviewed.

Animals↗
PubMed2002

Recurrent intracranial germinoma with dissemination along the ventricular catheter: a case report.

Most recurrences of intracranial pure germinoma occur at the primary site, ventricular wall or subarachnoid space. We report a rare case of intracranial germinoma that recurred along the shunt tube 17 years after prior ventriculoperitoneal shunt and radiotherapy. The recurrent tumor, verified histologically as a pure germinoma, involved the right frontal lobe along the ventricular catheter. In spite of subsequent surgery, radiation and chemotherapy, the tumor recurred repeatedly. Recurrence after such a long period highlights the necessity of long-term follow up for patients with germinoma. We also discuss possible causes of tumor dissemination along the ventricular catheter.

Adult↗