Search

The brain morphology of vertebrates exhibits huge evolutionary diversity, but one of the shared morphological features unique to vertebrate brain is laminar organization of neurons. Because the Reelin signal plays important roles in the development of the laminar structures in mammalian brain, investigation of Reelin signal in lower vertebrates will give some insights into evolution of vertebrate brain morphogenesis. Although zebrafish homologues of Reelin, the ligand, and Dab1, a cytoplasmic component of the signaling pathway, have been reported, the Reelin receptor molecules of zebrafish are not reported yet. Here, we sought cDNA sequence of zebrafish homologue of the receptors, vldlr and apoer2, and examined their expression patterns by in situ hybridization. Developmental gene expression pattern of reelin, dab1, vldlr, and apoer2 in the central nervous system of zebrafish was compared, and their remarkable expression was detected in the developing laminar structures, such as the tectum and the cerebellum, and also non-laminated structures, such as the pallium. The Reelin receptors exhibited different spatial and temporal gene expression. These results suggest a possibility that duplication and subsequent functional diversity of Reelin receptors contributed to the morphological and functional evolution of vertebrate brain.

A pyrolysis-GC/MS system incorporating with micro-UV irradiator (Xe–Hg lamp) was applied to the evaluation of the weatherability of the acrylic coating paints for house exterior walls. The deterioration of the materials during UV irradiation under thermal, and oxidative atmosphere was evaluated within a relatively short period of time with evolved gas analysis-mass spectrometry (EGA-MS) using a sub-milligram polymer sample. The EGA-MS thermograms indicated that both micro-UV irradiator with Xe–Hg lamp and weather meter with metal halide lamp caused similar photo, thermal, and oxidative degradation to the coating paint samples. Strong correlations between the results obtained by the UV/Py-GC/MS and that obtained by conventional weathering test using metal halide lamp was observed. It was suggested that UV/Py-GC/MS method could be used for compensating the conventional method by reducing the test period.

Reactive oxygen species (ROS) are involved in several cell death processes, including cerebral ischemic injury. We found that glutamate-induced ROS accumulation and the associated cell death in mouse hippocampal cell lines were delayed by pharmacological inhibition of autophagy or lysosomal activity. Glutamate, however, did not stimulate autophagy, which was assessed by a protein marker, LC3, and neither changes in organization of mitochondria nor lysosomal membrane permeabilization were observed. Fluorescent analyses by a redox probe PF-H(2)TMRos revealed that autophagosomes and/or lysosomes are the major sites for basal ROS generation in addition to mitochondria. Treatments with inhibitors for autophagy and lysosomes decreased their basal ROS production and caused a burst of mitochondrial ROS to be delayed. On the other hand, attenuation of mitochondrial activity by serum depletion or by high cell density culture resulted in the loss of both constitutive ROS production and an ROS burst in mitochondria. Thus, constitutive ROS production within mitochondria and lysosomes enables cells to be susceptible to glutamate-induced oxidative cytotoxicity. Likewise, inhibitors for autophagy and lysosomes reduced neural cell death in an ischemia model in rats. We suggest that cell injury during periods of ischemia is regulated by ROS-generating activity in autophagosomes and/or lysosomes as well as in mitochondria.

Background and Purpose— Lacunar infarction accounts for 25% of ischemic strokes, but the pathological characteristics have not been investigated systematically. A new experimental model of lacunar infarction in the miniature pig was developed to investigate the pathophysiological changes in the corticospinal tract from the acute to chronic phases. Methods— Thirty-five miniature pigs underwent transcranial surgery for permanent anterior choroidal artery occlusion. Animals recovered for 24 hours (n=7), 2 (n=5), 3 (n=2), 4 (n=2), 6 (n=1), 7 (n=7), 8 (n=2), and 9 days (n=1), 2 weeks (n=2), 4 weeks (n=3), and more than 4 weeks (n=3). Neurology, electrophysiology, histology, and MRI were performed. Seven additional miniature pigs underwent transient anterior choroidal artery occlusion to study muscle motor-evoked potentials and evaluate corticospinal tract function during transient anterior choroidal artery occlusion. Results— The protocol had a 91.4% success rate in induction of internal capsule infarction 286±153 mm 3 (mean±SD). Motor-evoked potentials revealed the presence of penumbral tissue in the internal capsule after 6 to 15 minutes anterior choroidal artery occlusion. Total neurological deficit scores of 15.0 (95% CI, 13.5 to 16.4) and 3.4 (0.3 to 6.4) were recorded for permanent anterior choroidal artery occlusion and sham groups, respectively ( P P Conclusions— This new model of lacunar infarction induces a reproducible infarct in subcortical white matter with a measurable functional deficit and evidence of penumbral tissue acutely.

Increased calcium sensitization mediated by Rho/Rho-kinase may be important in the pathogenesis of cerebral vasospasm. The effects of a highly selective Rho-kinase inhibitor, Y-27632, were investigated on spasmogen-induced contractions of canine basilar artery.Typical spasmogenic substances present after subarachnoid hemorrhage (SAH), including prostaglandin F2a (PGF2a), 12-deoxyphorbol 13-isobutyrate (DPB), sphingosylpho-sphorylcholine (SPC) and high K+, were used in the study. Isometric tension was recorded in canine basilar artery rings in vitro. Intracellular calcium concentration ([Ca2+]i) and contraction force were measured simultaneously in fura-2-loaded canine basilar artery strips. The myosin light chain (MLC) phosphorylation levels were measured by glycerol gel electrophoresis followed by Western blotting.Isometric tension recording revealed that the Rho-kinase inhibitor, Y-27632, dose-dependently inhibited vasocontraction induced by PGF2a and SPC, but not that induced by DPB. Simultaneous recordings of [Ca2+]i and tension revealed that the vasorelaxing effect of Y-27632 was not associated with changes in [Ca2+]i, suggesting that Y-27632 may inhibit calcium sensitization. Vasocontraction induced by DPB was not inhibited by Y-27632, but was inhibited by staurosporine. Phosphorylation of MLC was increased by PGF2a and SPC, and significantly inhibited by Y-27632, whereas such phosphorylation was increased by DPB, but not significantly inhibited by Y-27632.Several spasmogenic mediators released after SAH may cause vasospasm through Rho-kinase-mediated increase in calcium sensitization. Rho-kinase inhibitors, including Y-27632, may be effective for the prevention of cerebral vasospasm after SAH.

Destructive infiltration of invasive fungal sinusitis can easily occur into the central nervous system (CNS). Cerebral aneurysms associated with fungal infection are highly vulnerable to rupture, and can frequently and rapidly take a serious clinical course. We experienced a patient who twice developed cerebral aneurysm followed by rupture due to invasive fugal sinusitis. This 77-year-old man was admitted for progressive bilateral visual disturbance, which was initially treated as idiopathic hypertrophic pachymeningitis. The patient subsequently suffered subarachnoid hemorrhage (SAH) twice in only 12 days. Both SAH originated from different newly formed cerebral aneurysms. Trapping was performed for both ruptured aneurysms. Pathological examination of the resected aneurysms indicated the presence of fungi determined to be Aspergillus. This Aspergillus infection was also discovered inside the frontal sinus by endoscopic biopsy, so a regimen of antifungal agents was instituted. Prolonged antifungal therapy caused renal impairment, which ultimately led to the patient’s death. Autopsy detected no mycotic infiltration of the major cerebral arteries, except for the 2 ruptured cerebral aneurysms. However, prolonged mycosis of the CNS, such as in the deep part in the falx cerebri and in the small veins proximal to the tentorium cerebelli, was observed, indicating that mycosis invading the cranium is refractory even to long-term administration of antifungal agents. The present case strongly suggests that urgent and proactive definitive diagnosis is essential to successfully treat invasive paranasal sinus aspergillosis. If infiltration of the CNS is suspected, early surgical resection and antifungal therapy must be initiated immediately.

We previously showed that transplantation of brain microvascular endothelial cells (MVECs) greatly stimulated remyelination in the white matter infarct of the internal capsule (IC) induced by endothelin-1 injection and improved the behavioral outcome. In the present study, we examined the effect of MVEC transplantation on the infarct volume using intermittent magnetic resonance image and on the behavior of oligodendrocyte lineage cells histochemically. Our results in vivo show that MVEC transplantation reduced the infarct volume in IC and apoptotic death of oligodendrocyte precursor cells (OPCs). These results indicate that MVECs have a survival effect on OPCs, and this effect might contribute to the recovery of the white matter infarct. The conditioned-medium from cultured MVECs reduced apoptosis of cultured OPCs, while the conditioned medium from cultured fibroblasts did not show such effect. These results suggest a possibility that transplanted MVECs increased the number of OPCs through the release of humoral factors that prevent their apoptotic death. Identification of such humoral factors may lead to the new therapeutic strategy against ischemic demyelinating diseases.

Background: De novo aneurysm formation after intracranial anastomotic surgery is a relatively rare complication with fewer than 20 reported cases, and the mechanism is still unclear. Case Description: A 63-year-old male treated for symptomatic internal carotid artery occlusion developed de novo aneurysms twice after anastomoses first of the superficial temporal artery-middle cerebral artery and second of the external carotid artery-radial artery-middle cerebral artery over a 10-year period. The first de novo aneurysm was successfully resected with pathological diagnosis of true aneurysm. The second de novo aneurysm thrombosed naturally after gradual growth. Genetic testing of the patient revealed the c.14576G>A (p.R4859K) variant in ring finger protein 213, which is a susceptibility gene for moyamoya disease. Conclusions: This genetic variant was probably involved in the repeated de novo aneurysm formation, and this case represents a rare phenotype of the genetic variant.

Dopamine plays a key role in the regulation of sleep–wake states, as revealed by the observation that dopamine-releasing agents such as methylphenidate have wake-promoting effects. However, the precise mechanisms for the wake-promoting effect produced by the enhancement of dopamine transmission are not fully understood. Although dopamine D1, D2, and D3 receptors are known to have differential effects on sleep architecture, the role of D4 receptors (D4Rs), and particularly the influence of D4R activation on the sleep–wake state, has not been studied so far. In this study, we investigated for the first time the effects of two structurally different D4R agonists, Ro 10-5824 and A-412997, on the sleep–wake states in rats. We found that both D4R agonists generally increased waking duration, and conversely, reduced non-rapid eye movement (NREM) sleep duration in rats. The onset of NREM sleep was also generally delayed. However, only the A-412997 agonist (but not the Ro 10-5824) influenced rapid eye movement sleep onset and duration. Furthermore, these effects were accompanied with an enhancement of EEG spectral power in the theta and the gamma bands. Our results suggest the involvement of dopamine D4R in the regulation of sleep–wake states. The activation of the D4R could enhance the arousal states as revealed by the behavioral and electrophysiological patterns in this study. Dopamine D4R may contribute to the arousal effects of dopamine-releasing agents such as methylphenidate.

Irradiating group-III (B, Al, Ga)-doped Czochralski (CZ)-grown Si substrates as well as B-doped magnetic Czochralski (MCZ)-grown and floating-zone (FZ)-grown Si substrates with 10 MeV protons or 1 MeV electrons, we investigate both the reduction in the hole concentration and the conversion of p type to n type using Hall-effect measurements. In all the 10 Ω cm CZ-Si, the density of each acceptor species is reduced by irradiation, and finally the conversion occurs with 1017 cm-2 fluence of 1 MeV electrons or with 2.5×1014 cm-2 fluence of 10 MeV protons. In 10 Ω cm MCZ-Si and 10 Ω cm FZ-Si, on the other hand, the conversion does not occur under the same conditions. Moreover, the reduction in the hole concentration for the FZ-Si is much less than the others. From these results, it is elucidated that the conversion as well as the reduction in the hole concentration is strongly dependent on the concentration of oxygen in Si, not on the type of acceptor species in Si. Therefore, the p-type FZ-Si substrate is appropriate for radiation-resistant space solar cells such as n+/p/p+ Si solar cells and upcoming III–V tandem solar cells on n+/p Si substrates.

The purpose of this set of studies is to design a minimally invasive, reproducible stroke model in the gyrencephalic brain. This paper provides information on both surgical technique and methods of quantification of ischemic damage to both gray and white matter in the miniature pig.Sixteen male miniature pigs were randomly divided into three groups and underwent transcranial surgery involving a frontotemporal approach with orbital rim osteotomy for permanent middle cerebral artery occlusion (MCAO; five animals), permanent internal carotid artery occlusion (ICAO; six animals), and a sham operation (five animals). Histological mapping and magnetic resonance (MR) imaging were used to delineate the areas of ischemic damage. The volumes of infarction measured directly from MR images were 16.2 +/- 1.1, 1.5 +/- 0.5, and 0.0 +/- 0.0 cm3 (mean +/- standard deviation [SD], p0.001) in the MCAO, ICAO, and sham-operated groups, respectively. The areas of ischemia identified through histological analysis and MR imaging showed a good correlation (r2 = 0.86, p0.0001). Immunohistochemical staining with an amyloid precursor protein (APP) antibody was used to evaluate axonal damage and calculate a total APP score for axonal damage of 44.8 +/- 2.9 in the MCAO, 13.2 +/- 6.6 in the ICAO, and 0.0 +/- 0.0 (mean +/- SD, p0.002) in the sham-operated animals.This new model of focal cerebral ischemia induces a reproducible amount of ischemic damage in both gray and white matter, and has significant utility for studies of the pathophysiology of ischemia in the gyrencephalic brain and for assessment of the therapeutic efficacy of drugs prior to the initiation of human clinical trials.

Background and Purpose— To evaluate whether delayed treatment with the antiplatelet agent cilostazol reduces the volume of infarction in the gray and white matter in a rodent model of permanent focal cerebral ischemia and to explore the mechanism of the neuroprotective effect in vivo. Methods— Cilostazol (30 or 50 mg/kg) or vehicle was administered by gavage 30 minutes and 4 hours after the induction of cerebral ischemia by permanent occlusion of the left middle cerebral artery (MCA). Animals were euthanized 24 hours after MCA occlusion, and the volume of gray matter damage was evaluated by quantitative histopathology. Axonal damage was determined with amyloid precursor protein immunohistochemistry. Dynamic susceptibility contrast MRI was used to assess regional cerebral blood volume (CBV) and cerebral blood flow (CBF). Results— Treatment with the higher dose of cilostazol (50 mg/kg) significantly reduced the volume of gray matter damage and axonal damage in the cerebral hemisphere by 45.0% ( P P P Conclusions— Treatment with cilostazol significantly reduced the gray and white matter damage associated with permanent focal ischemia. Cilostazol improved CBV and CBF in the peri-infarct area. The major action of cilostazol is to increase perfusion in the ischemic penumbra.

Background: Cerebral vasospasm is one of the important pathological phenomena which influence morbidity and mortality following subarachnoid haemorrhage. Reactive oxygen species (ROSs) generated by the autoxidation of oxyhemoglobin to methemoglobin may be one of the essential factors in the pathogenesis of cerebral vasospasm. The direct vasocontractile effects of hydrogen peroxide (H2O2), superoxide anion (O2 −), and hydroxyl radical (*OH) on the canine basilar artery and the inhibitory effects of MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one), a new *OH scavenger, were investigated. Method: Isometric tension was recorded in basilar artery rings from dogs in vitro. H2O2, pyrogallol (O2 − donor), and vitamin C (VitC)/Fe2+ (*OH-generating system) were used to generate the ROSs. Findings: H2O2 (10 μmol/L), pyrogallol (10 μmol/L), and VitC/Fe2+ (100 μmol/L each) induced fast onset and transient, slow onset and transient, and sustained contraction, respectively, in the canine basilar artery. Contractions induced by H2O2 were almost completely inhibited by pre-incubation with catalase (800 U/mL) and those by pyrogallol with superoxide dismutase (150 U/mL), but neither with MCI-186 (10 μmol/L). The contraction induced by VitC/Fe2+ was clearly inhibited by pre-incubation with MCI-186, but not with catalase or superoxide dismutase. Interpretation: ROSs have direct vasocontractile effects on the canine basilar artery in vitro, but different ROSs have different contractile characteristics. Such contractions might be related to the pathophysiology of cerebral vasospasm. MCI-186 had a clear and selective inhibitory effect against *OH-induced contraction in vitro. Comparison of different radical scavengers may be important in pharmacological assessment, especially targeted on cerebral vasospasm.

Cell cycle proteins play key roles in cell survival or death under pathological conditions. Expression of growth arrest and DNA damage-inducible protein, GADD34 and proliferating cell nuclear antigen (PCNA) have been investigated in the core and peri-infarct zone at 2 and 24 h after middle cerebral artery occlusion (MCAO). At these times after MCAO, numerous GADD34-positive cells were present, particularly in the peri-infarct zone (e.g. 24 +/- 4 and 52 +/- 6 immunopositive cells/0.25 mm2 at 2 and 24 h, respectively, in cortex). PCNA-immunopositive cells were barely detectable in the peri-infarct zone at 2 h; however, numerous PCNA-immunopositive cells were present in this zone by 24 h (0.7 +/- 0.3 and 10.6 +/- 1.5 immunopositive cells/0.25 mm2, respectively) as well as in the adjacent cortex and in the contralateral cingulate cortex. Most GADD34-immunopositive cells coexpressed the neuronal marker Neu-N with a smaller number coexpressing the microglial marker, Mrf-1. Evidence of morphologically 'abnormal' and 'normal' GADD34 immunopositive neurons was found within the peri-infarct zone. The majority of PCNA immunopositive cells were Mrf-1 positive with a smaller number Neu-N positive. Double-labelling revealed colocalization of GADD34 and PCNA in some cells within the peri-infarct zone and in the ependymal cells lining the ventricles. The presence of GADD34 and PCNA in a key anatomical location pertinent to the evolving ischaemic lesion indicates that GADD34, either alone or in combination with PCNA, has the potential to influence cell survival in ischaemically compromised tissue.

The optimal surgical procedure (direct, indirect, or combined anastomosis) for management of moyamoya disease is still debated. We evaluated the outcome of our broad area revascularization protocol, the Tokyo Daigaku (The University of Tokyo) (TODAI) protocol, analyzing the relative importance of direct, indirect, and combination revascularization strategies to identify the optimal surgical protocol.The TODAI protocol was used to treat 65 patients with moyamoya disease (91 hemispheres, including 48 in 29 childhood cases collected during 1996-2012). The TODAI protocol combined direct superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis with indirect revascularization using encephalo-myo-synangiosis (EMS) for patients ≥10 years old or indirect revascularization using encephalo-duro-arterio-synangiosis (EDAS) with EMS for patients ≤9 years old. Clinical outcome was evaluated retrospectively. Digital subtraction angiography was performed for postoperative evaluation of revascularization in 47 patients (62 hemispheres; 27 adults and 35 children). Based on the relative contribution of additional flow from each revascularization path, 4 revascularization patterns were established.The mean follow-up period was 90 months in children and 72 months in adults. Perioperative complications were seen in 4 of 48 operations in children and 1 of 43 operations in adults. Except for 1 child with recurrent transient ischemic attacks and 1 adult with intracerebral hemorrhage, the patients showed excellent clinical outcomes. Postoperative digital subtraction angiography evaluation showed that in STA-MCA anastomosis + EMS cases (34 hemispheres; 25 adults and 9 children), STA-MCA anastomosis provided greater revascularization than EMS (STA-MCA anastomosisEMS) in 7 hemispheres, the opposite was true (STA-MCA anastomosisEMS) in 14 hemispheres, an equivalent contribution to revascularization (STA-MCA anastomosis ≈ EMS) was present in 12 hemispheres, and no functioning anastomosis was present in 1 hemisphere. In cases of EDAS + EMS (28 hemispheres; 2 adults and 26 children), all hemispheres showed revascularization: EDAS was dominant to EMS (EDASEMS) in 1 hemisphere, the opposite (EMSEDAS) was true in 14 hemispheres, and EDAS was equivalent to EMS (EDAS ≈ EMS) in 13 hemispheres. EMS plus direct or indirect anastomosis is an effective surgical procedure in adults and children.The TODAI protocol provided efficient revascularization and yielded excellent results in preventing strokes in patients with moyamoya disease with very few complications. EMS had a main role in revascularization in each of the combined techniques.

Background Quasi-moyamoya disease (MMD) and MMD (definite MMD) have similar cerebral angiographic features, but whether these related diseases have similar etiology or genetic background remains unclear. Recently, we have reported that the recently identified MMD susceptibility gene variant RNF213 c.14576G>A (rs112735431) was associated with atherosclerotic intracranial major artery stenosis/occlusion. The present study investigated the occurrence of RNF 213 c.14576G>A in patients with nonatherosclerotic quasi-MMD. Methods This study was a 2-hospital–based case–control study conducted at the Department of Neurosurgery, The University of Tokyo Hospital and Kanto Neurosurgical Hospital. A total of 87 Japanese patients who agreed to participate in this study were enrolled among both new and revisiting outpatients from October 2011 to December 2013 as follows: 78 patients with definite MMD and 9 patients with nonatherosclerotic quasi-MMD. Results The 9 patients with nonatherosclerotic quasi-MMD included 3 patients with previous irradiation, 2 with hyperthyroidism, 1 with Turner syndrome, 1 with meningitis, 1 with Behcet disease, and 1 with idiopathic pachymeningitis. The 78 patients with definite MMD included 66 patients (84.6%) with the c.14576G>A variant (64 heterozygotes and 2 homozygous). In contrast, no patients with nonatherosclerotic quasi-MMD had the variant. Conclusions Nonatherosclerotic quasi-MMD did not have RNF213 c.14576G>A variant. Moyamoya disease and related diseases might be classified by genetic analysis of the RNF213 c.14576G>A genotype. Further larger studies are required to confirm the present findings.

Here, we present a case of a 55-year-old woman with a 10-year history of hemifacial spasm accompanied by 1-month ipsilateral paroxysmal otalgia. Magnetic resonance imaging revealed the presence of vessels around the facial nerve root. Surgical exploration via suboccipital retromastoid craniotomy showed converging compression of the facial nerve root and intermediate nerve from both sides by an anterior inferior cerebellar artery loop. The patient's hemifacial spasm and ipsilateral otalgia were completely relieved after microvascular decompression of the facial nerve root and intermediate nerve. Intraoperative findings and the postoperative result of this case confirmed that vascular compression of the intermediate nerve was the exclusive cause of paroxysmal otalgia. The presence of ipsilateral hemifacial spasm, combined with preoperative neuroimaging studies, contributed to the diagnosis of intermediate nerve neuralgia. Microvascular decompression should be considered for the management of patients with intermediate nerve neuralgia.

Background and Purpose — The neuroprotective efficacy of an intravenous formulation of the antioxidant ebselen has been comprehensively assessed with specific regard to conventional quantitative histopathology, subcortical axonal damage, neurological deficit, and principal mechanism of action. Methods — Transient focal ischemia (2 hours of intraluminal thread-induced ischemia with 22 hours of reperfusion) was induced in the rat. Ebselen (1 mg/kg bolus plus 1 mg/kg per hour IV) or vehicle was administered at the start of reperfusion and continued to 24 hours. Neurological deficit was assessed 24 hours after ischemia. Gray matter damage was evaluated by quantitative histopathology. Axonal damage was determined with amyloid precursor protein immunohistochemistry used as a marker of disrupted axonal flow and Tau-1 immunohistochemistry to identify oligodendrocyte pathology. Oxidative damage was determined by 8-hydroxy-2′-deoxyguanosine (8-OHdG) and 4-hydroxynonenal (4-HNE) immunohistochemistry. Results — Ebselen significantly reduced the volume of gray matter damage in the cerebral hemisphere (by 53.6% compared with vehicle, P P P P P P Conclusions — Delayed (2-hour) treatment with intravenous ebselen significantly reduced gray and white matter damage and neurological deficit associated with transient ischemia. The reduction in tissue displaying evidence of oxidative stress suggests that the major mechanism of action is attenuation of free radical damage.

The effect of low-energy oxygen ion irradiation during Ga focused ion beam (FIB) SIMS analyses has been investigated. The positive secondary ion yield in Ga FIB-SIMS analysis was increased dramatically due to the bombardment of O2+ ions. The degree of yield enhancement increased with increased oxygen doses until it became constant above 1.5 × 1016 atoms cm−2, indicating saturation of the oxygen concentration at the analysis depth. Secondary ion images of a line-and-space pattern of boron in the silicon matrix have been obtained with 3 keV and 0.7 keV O2+ ions. It was revealed that the enhancement effect of irradiation with 0.7 keV O2+ ions is of the same degree as that with the 3 keV O2+ ions. From the perspective of sensitivity, however, a lower energy beam is more effective because the sputtering of the sample surface by the O2+ irradiation is reduced, resulting in a greater volume for analysis by the Ga+ beam. A secondary ion image of 0.6 at.% boron from the 0.5 µm line width with an analysis depth of 6 nm has been obtained readily by irradiation of the 0.7 keV O2+ beam. Copyright © 2001 John Wiley & Sons, Ltd.

Two cases of recurrent pilocytic astrocytoma with leptomeningeal dissemination (LMD) are described. A 6-year-old boy presented with a cerebellar tumor, which was subtotally removed. Tumor recurrence with LMD occurred 4 years later. Reoperation for tumor removal followed by craniospinal irradiation stabilized the LMD over 5 years. A 4-year-old girl presented with a chiasmatic-hypothalamic tumor. Partial removal of the tumor was followed by radiation therapy. Tumor regrowth with LMD occurred 4 years later and was managed by reoperation, chemotherapy and radiotherapy. Tumor recurrence with LMD can be stabilized by multimodal treatment without tumor progression.

We report the case of a patient with an olfactory neuroblastoma which occupied the sphenoid sinus with nasal and suprasellar extension. Presenting symptoms included diminished visual acuity in the right eye. Computed tomography (CT) and magnetic resonance (MR) imaging demonstrated a tumor that had destroyed most of the sphenoid sinus, extending to the nasal cavity and suprasellar region. The patient underwent surgery via a fronto-temporal approach. An extensive review of the literature revealed approximately 300 cases of olfactory neuroblastoma, however, only two of these cases involved the sphenoidal region. This tumor is not thought to be derived from the olfactory neuroepithelium, but rather from neural crest tissue surrounding the sphenoid sinus.

The expression of the α and β isoforms of phosphatidylinositol transfer protein (PI-TP α and PI-TP β ) in the adult rat brain was examined by in situ hybridization analysis with isoform-specific RNA probes. PI-TP α mRNA was detected in rather restricted regions of the brain whereas PI-TP β mRNA was widely distributed in the brain. PI-TP α mRNA signals were remarkable in neocortex layers II/III and V/VI, Purkinje cell layer, deep cerebellar nuclei of the cerebellum, red nucleus and most part of brain stem. Low levels of PI-TP α transcript were present in CA3 of the hippocampus, ventral and dorsal thalamic nuclei, and motoneurons of spinal cord. No hybridization signals was obtained in the olfactory bulb, basal ganglia, amygdala, hypothalamus, and pituitary gland. In contrast, strong signals of PI-TP β mRNA were detected in the dentate gyrus. The β isoform mRNA was moderately expressed in olfactory bulb, layers II/III of the neocortex, striatum, CA1–CA4 regions of the hippocampus, medial habenula, cerebellum, amygdala, hypothalamus, spinal cord, and pituitary gland. Thalamus and brain stem contained relatively low, but significant levels of PI-TP β transcript. The distinct distribution of PI-TP α and PI-TP β mRNAs suggests different functional roles for each of the gene products in the mature nervous system. © 1997 Elsevier Science B.V. All rights reserved.

The clinical and histological characteristics of oligodendroglioma and oligoastrocytoma were investigated in patients, mainly adults with supratentorial tumors, who were treated with surgery and radiotherapy, and with chemotherapy for recurrent, anaplastic tumors, or both. The median survival time was 13.2 years for oligodendroglioma (four patients), 12.7 years for anaplastic oligodendroglioma (five patients), 13.5 years for oligoastrocytoma (seven patients), and 4.8 years for anaplastic oligoastrocytoma (four patients). Two of three recurrent oligodendrogliomas and two of two recurrent oligoastrocytomas showed malignant transformation. Minigemistocytes were sometimes recognized in recurrent tumors and had a sinister prognosis. Oligodendroglioma and oligoastrocytoma may transform into each other at recurrence.

Oculomotor nerve palsy (ONP) due to internal carotid-posterior communicating artery (PcomA) aneurysm generally manifests as partial nerve palsy including pupillary dysfunction. In contrast, infundibular dilatation (ID) of the PcomA has no pathogenic significance, and mechanical compression of the cranial nerve is extremely rare. We describe a 60-year-old woman who presented with progressive ptosis due to mechanical compression of the oculomotor nerve by an ID of the PcomA. Three-dimensional computer graphics (3DCG) accurately visualized the mechanical compression by the ID, and her ptosis was improved after clipping of the ID. ID of the PcomA may cause ONP by mechanical compression and is treatable surgically. 3DCG are effective for the diagnosis and preoperative simulation.

A modified method of injection into the cerebellomedullary (CM) cistern of mice was developed based on fixation of the mouse with a special mask under inhalation anesthesia, and exposure of the sagittal suture of the cranium and midline of the nape to allow us to visualize injection point directly. The accuracy of the modified method was evaluated using the temporal and spatial intracranial distribution of dye by intracisternal injection of 6- microliter methylene blue aqueous solution. A high concentration of dye was found in the CM cistern, the ventral cisterns, and intracranial proximal portion of the main cranial nerves at 1 hour after injection. The color of the dye in the CM cistern and the ventral cisterns was lighter, and the dye had reached the intracranial distal portion of the main cranial nerves at 6 hours after injection. The dye was completely eliminated by cerebrospinal fluid (CSF) circulation at 24 hours after injection. No severe brain injury was found in any of the 20 mice. Intracisternal injection was successful in all 14 mice sacrificed 1 hour or 6 hours after injection according to the confirmation of dye distribution. The effects of central administration of endothelin-1 (ET1) were evaluated on cerebral blood supply, constriction of cerebral arteries, and change of respiration in mice. Three doses of ET1 were studied: 2 micrograms (0.8 nmol), 4 micrograms (1.6 nmol), and 6 micrograms (2.4 nmol). Cerebral blood flow (CBF) was monitored for 60 minutes following injection using a laser Doppler probe. Intracisternal ET1 injection induced dose-dependent reduction of CBF, constriction of cerebral arteries, and respiratory depression in mice. This modified method of injection into the CM cistern under direct visualization provides accurate and reproducible injection into the CSF, and can be used to investigate the effects of various chemical substances on the central nervous system in mice.

Phosphatidylinositol synthase (CDP-1,2-diacyl-sn-glycerol: 3-phosphatidyltransferase, EC 2.7.8.11) catalyzes the formation of phosphatidylinositol and CMP from CDP-diacyl-glycerol and myo-inositol. We have cloned a phosphatidylinositol synthase cDNA from rat brain by functional complementation of the yeast pis mutation, which is defective in phosphatidylinositol synthase. The deduced protein comprised 213 amino acids with a calculated molecular mass of 23 613 Da. The predicted protein sequence is highly homologous to the previously determined yeast phosphatidylinositol synthase sequence. The cDNA hybridized to a 1.7-kb mRNA that was abundantly expressed in rat brain and kidney.

Hexacene (HEX) and derivatives such as dihydrohexacene and dihydroxyhexcane quinone were synthesized and thin films of them were prepared by the sublimation method. The structure and conductivity of the films both before and after doping with iodine were studied. The doped HEX film showed the conductivity of 3 × 10−2 S/cm at room temperature, which was lower than expected since the conductivity of highly ordered pentacene was above 100 Ω−1 cm−1. The reason for the low conductivity was considered to be the disorder in molecular alignment since the HEX film showed an amorphous structure. A reversible change in the conductivity of the HEX film was observed in air and in vacuum.

A 6-year-old boy presented with a pontine abscess initially misdiagnosed as brainstem glioma, but he deteriorated rapidly and developed new symptoms of respiratory distress. Magnetic resonance (MR) imaging revealed a rapidly growing mass lesion in the pons. Microsurgical evacuation of the abscess via a suboccipital retromastoid approach resulted in neurological improvement and resolution of the lesion on MR images. Brainstem abscess can be successfully treated with early, accurate diagnosis based on MR imaging and appropriate microsurgical and antibiotic management.

Subcortically projecting neurons and callosally projecting ones are distinct neuronal pools in the cerebral cortex of the rodents. However, cortical efferent neurons are known to project multiple targets transiently by plural collateral axons. These plural axons are eliminated during prenatal and postnatal development. In the cerebral cortex of the Reelin-deficient mouse, reeler, which is caused by mutation of the reelin gene, cortical efferent neurons are ectopically distributed. However, it is still unknown whether cortical efferent neurons in the reeler mouse lose surplus collateral axons or maintain them during developmental periods. If surplus collaterals of malpositioned cortical neurons are not eliminated, neurons projecting subcortically may project their axons to the contralateral hemisphere. To test this plausible hypothesis, we made double injections of two fluorescent dyes, Fast Blue and Diamidino yellow dihydrochloride into two of three regions, i.e., upper cervical cord, ventral lateral thalamic nucleus, and contralateral motor cortex of the normal and reeler mice, to label corticospinal, corticothalamic and callosal commissure neurons in the motor cortex, retrogradely. No double labeled neurons were identified in the motor cortex of the normal and reeler mice, although the distribution patterns of these cortical efferent neurons were completely different between normal and reeler mice. These findings strongly suggest that collateral elimination of cortical efferent neurons during developing periods are not affected in this mutant mouse.

Cerebral hemorrhage is a common lethal complication associated with left ventricular assist device (LVAD) management. We performed cerebral angiography on patients with LVAD who developed cerebral hemorrhage and determined that ruptured aneurysms were the cause in some cases. Endovascular management of patients with LVAD can be a therapeutically useful approach for cerebral hemorrhage caused by aneurysm rupture.

Prenatal exposure of methylazoxymethanol acetate, a DNA methylating agent, to pregnant rats on embryonic day 15 is known to produce hippocampal malformation and laminar disorganization of the cerebral cortex. However, there are few studies to demonstrate developmental processes of abnormal structures in the hippocampus. In the present study, we examined complete serial sections of rat brains on postnatal day 0 to 2, which pretreated with methylazoxymethanol acetate on embryonic day 15. At birth, massive cellular clusters were found under the white matter of the cerebral cortex and then, a part of these clusters entered into the hippocampal CA1 sector on postnatal day 2. These ectopic cellular clusters in the CA1 were immunoreactive to anti-calbindin antibody, suggesting that the origin of these cellular clusters is equivalent to that of the cortical layer II/III neurons. Next, we injected FluoroGold into the lateral septal nucleus to examine hippocampo-septal projection. FluoroGold-labeled neurons were scattered in the ectopic cellular cluster, implying that CA1 pyramidal neurons project normally to the lateral septal nucleus. In conclusion, a majority of neurons found in the ectopic cellular cluster caused by prenatal methylazoxymethanol treatment is derived from cortical neurons, and some intrinsic pyramidal neurons in the CA1 of hippocampus are scattered throughout the ectopic cellular cluster.

Objective Surface-rendered three-dimensional (3D) 1.5-T magnetic resonance (MR) imaging is useful for presurgical simulation of microvascular decompression. This study compared the sensitivity and specificity of 1.5- and 3.0-T surface-rendered 3D MR imaging for preoperative identification of the compression vessels of trigeminal neuralgia. Methods One hundred consecutive patients underwent microvascular decompression for trigeminal neuralgia. Forty and 60 patients were evaluated by 1.5- and 3.0-T MR imaging, respectively. Three-dimensional MR images were constructed on the basis of MR imaging, angiography, and venography data and evaluated to determine the compression vessel before surgery. MR imaging findings were compared with the microsurgical findings to compare the sensitivity and specificity of 1.5- and 3.0-T MR imaging. Results The agreement between MR imaging and surgical findings depended on the compression vessels. For superior cerebellar artery, 1.5- and 3.0-T MR imaging had 84.4% and 82.7% sensitivity and 100% and 100% specificity, respectively. For anterior inferior cerebellar artery, 1.5- and 3.0-T MR imaging had 33.3% and 50% sensitivity and 92.9% and 95% specificity, respectively. For the petrosal vein, 1.5- and 3.0-T MR imaging had 75% and 64.3% sensitivity and 79.2% and 78.1% specificity, respectively. Complete pain relief was obtained in 36 of 40 and 55 of 60 patients undergoing 1.5- and 3.0-T MR imaging, respectively. Conclusions The present study showed that both 1.5- and 3.0-T MR imaging provided high sensitivity and specificity for preoperative assessment of the compression vessels of trigeminal neuralgia. Preoperative 3D imaging provided very high quality presurgical simulation, resulting in excellent clinical outcomes.

Ischemic insults affecting the internal capsule result in sensory-motor disabilities which adversely affect the patient's life. Cerebral endothelial cells have been reported to exert a protective effect against brain damage, so the transplantation of healthy endothelial cells might have a beneficial effect on the outcome of ischemic brain damage. In this study, endothelin-1 (ET-1) was injected into the rat internal capsule to induce lacunar infarction. Seven days after ET-1 injection, microvascular endothelial cells (MVECs) were transplanted into the internal capsule. Meningeal cells or 0.2% bovine serum albumin-Hank's balanced salt solution were injected as controls. Two weeks later, the footprint test and histochemical analysis were performed. We found that MVEC transplantation improved the behavioral outcome based on recovery of hind-limb rotation angle (P

Cerebral hemorrhage is one of the common complications associated with left-ventricular-assist device (LVAD) treatment and leads to a high mortality rate because of excessive bleeding due to frequently unknown causes. Cerebral angiography is used to diagnose cerebrovascular events and is well recognized as being very useful for this purpose. We performed a cerebral angiography for a patient with an LVAD who developed cerebral hemorrhage, and the hemorrhagic source was clearly identified. The patient underwent successful neurosurgical treatment, which was followed by heart transplantation.

Experimental cerebral ischemia has been reportedly alleviated by the immunosuppressive agent cyclosporin A (CsA). Cyclophilin C-associated protein (CyCAP) was proposed to be an endogenous equivalent of CsA; CsA- and CyCAP-targeting protein cyclophilin C have attracted extensive attention regarding their ischemia-alleviating mechanisms. In this study we have introduced the specific CyCAP antibody for evaluating its distribution in the rat ischemic brain after middle cerebral artery occlusion. During the recovery of cerebral ischemia in rats, CyCAP was highly expressed in the activated microglia/macrophages in the ischemic lesion. However, it remains unknown what roles CyCAP plays in the activation of macrophage phagocytosis. Thus, we studied CyCAP function using a RAW264.7 macrophage cell line. When we expressed CyCAP-GFP and cyclophilin C-FLAG in RAW264.7 cells, we found that CyCAP and cyclophilin C make a complex, which is competitively inhibited by CsA. Consistently, in immunoprecipitates by anti-calcineurin antibody, cyclophilin C and CyCAP were detected, and CyCAP pulled down NFATc1, suggesting that both CyCAP and cyclophilin C form a complex with calcineurin and NFATc1. When CyCAP was adenovirally overexpressed in RAW cells, NFAT staining increased over the nucleus. Furthermore, calcineurin and IL-2 were increased with time. Thus, CyCAP appears to control macrophage functions by activating NFAT and the resultant IL-2 production. With a protein phosphatase inhibitor PhoSTOP, NFAT was localized more to the cytoplasm, and phagocytosis was decreased strikingly. Thus, we suggest that in a CyCAP-cyclophilin C pathway for macrophage activation, calcineurin phosphatase activity is essential for the phagocytosis activity via dephosphorylation of NFATc1.

Donor doping of thin films of pentacene (PEN) with alkaline metals such as sodium, potassium, and rubidium was carried out. Drastic changes in conductivities of PEN films from an insulator to an n‐type semiconductor due to the doping was observed. Maximum conductivity of 2.8 Ω−1 cm−1 was shown in the film doped with rubidium. Alkaline metal doping of thin films of other acene compounds such as tetracene and hexacene was also performed.

Structure and electrical conductivities of thin films of acene compounds doped with iodine were studied. In particular, doping of thin films of pentacene (PEN) with iodine caused characteristic changes in structure and electrical conductivity. The doped films exhibited high lateral conductivity above 102 S/cm with high anisotropy of 108 and well-defined layered structure in which iodine molecules intercalated between molecular layers of PEN. Metallic transport appeared in the highly ordered film at temperatures below 240 K. Transport behavior, lateral and perpendicular to the plane, was explained by two-dimensional (2D) variable range hopping (VRH) and by the tunneling mechanism, respectively. These electrical properties were strongly correlated with the degree of molecular orientation in the film.

Structural studies on highly conductive thin films of pentacene (PEN) were carried out by x‐ray and electron diffraction methods. The ultrathin film before and after doping with iodine was confirmed to consist of single crystalline domains, and the lattice parameters were determined. Drastic elongation along the c axis as a result of doping was observed, while the a‐b plane did not change during doping. The intercalation of iodine molecules between molecular layers of PEN was confirmed.

Studies on electrical properties of highly ordered and amorphous thin films of pentacene (PEN) doped with iodine have been made. Highly ordered film heavily doped with iodine (PEN1I2.2) showed electrical conductivity of 150 Ω−1 cm−1 with a hole mobility of 0.2 to 1 cm2 V−1 s−1 at room temperature. Metallic temperature dependence of the conductivity of the film from 240 to 4 K was observed as the first metallic transport phenomenon ever noted in an acenic compound. In contrast, amorphous film of PEN doped with iodine showed a conductivity of 10−3 Ω−1 cm−1 with an estimated hole mobility of 2×10−5 cm2 V−1 s−1 and semiconductive transport. These results revealed that the electrical properties of PEN thin films are strongly correlated with the degree of molecular orientation.

Object Encephalomyosynangiosis (EMS) is a surgical treatment for moyamoya disease that is widely used to provide increased intracranial blood flow via revascularization by arterial anastomosis from the external carotid artery. However, the angiogenic mechanism responsible for the revascularization induced by EMS has not been systematically evaluated. In this study the authors investigated the chronological angiogenic changes associated with EMS to clarify the favorable factors and identify revascularization mechanisms by using an experimental internal carotid artery occlusion (ICAO) model in the miniature pig. Methods Fourteen miniature pigs were used, 11 of which underwent ICAO before transcranial surgery for EMS was performed. Animals were allowed to recover for 1 week (4 pigs) or 4 weeks (7 pigs) after EMS. Control group animals were treated in the same way, but without occlusion (3 pigs). Magnetic resonance imaging, angiography, and histological investigation were performed. Results One week after EMS, on histological examination of both the ICAO and control groups it was found that the transplanted temporal muscle had adhered to the arachnoid via a granulation zone, which was enriched with immune cells such as macrophages associated with the angiogenic process. Four weeks after EMS, angiography and histological examination of the ICAO group showed patent anastomoses between the external carotid artery and the cortical arteries without any detectable boundary between the temporal muscle and the cerebral cortex. In contrast, histological examination of the control group found scar tissue between the cerebral cortex and temporal muscle. Conclusions The initial step for formation of anastomoses resembles the process of wound healing associated with repair processes such as active proliferation of macrophages and angiogenesis within the new connective tissue. Functional revascularization requires a suitable environment (such as tissue containing vascular beds) and stimulus (such as ischemia) to induce vascular expansion.

Intratumoral bleeding from a meningioma is very rare. We herein report a case of a foramen magnum meningioma which presented in association with intratumoral bleeding. A 49-year-old female who had been suffering from occipital headache and shoulder pain on neck motion was referred to our hospital to undergo treatment for a tumor located in the posterior fossa. Magnetic resonance imaging (MRI) demonstrated a foramen magnum meningioma which originated at the lower clivus and extended to the C2 level of the vertebral column. Marked compression and distortion of the medulla oblongata and spinal cord was also noted. Surgery was therefore planned. The patient thereafter suffered from a sudden onset of headache, vomiting and hoarseness, and was transferred to our hospital. A computed tomography (CT) showed intratumoral bleeding, which extended to the subarachnoid space and the fourth ventricle. The tumor, as well as the massive hematoma, were both immediately removed. The histological diagnosis was meningothelial meningioma. We also reviewed the pertinent literature and propose the possible mechanism for such tumor bleeding in this particular location in which the blockage of the cerebrospinal fluid caused a craniovertebral pressure gradient, which thus resulted in intratumoral bleeding.

Tumor cell infiltration around the tumor tissue in glioblastoma was investigated in 13 patients with glioblastoma who underwent gross total tumor removal. Thirty-four glioblastoma cases were operated on between January 1988 and December 1995. T1-weighted magnetic resonance imaging (MRI) with gadolinium enhancement was used to measure tumor size, and T2-weighted MRI to detect perilesional edema. Biopsy samples of surrounding tissue taken after tumor removal were histologically examined. Small tumors ( 6 cm diameter) with moderate or high perilesional edema had intensive tumor cell infiltration.

A novel fluorescence probe, 2-[6-(4'-hydroxy) phenoxy-3H-xanthen-3-on-9-yl] benzoic acid (HPF) was used to investigate the generation of highly reactive oxygen species (hROS) under ischemia both in vitro and in vivo. In the in vitro study, HT 22 cells were used to demonstrate that was predominantly detected in the cytoplasm, which coincides with the location of the mitochondria and then its HPF fluorescence gradually increased from 6 to 24 h due to glutamate induced oxidative stress. In the in vivo study, the permanent and transient middle cerebral artery occlusion (MCAO) was induced in rats. Brain slices were incubated in an artificial medium containing HPF. The area of enhanced HPF fluorescence existed in both the ischemic core and the peri-infarct area at 4h after MCAO in both permanent and transient MCAO models. The area extended beyond the boundary of the ischemic damage into biochemically viable tissue. The enhanced fluorescent intensity following transient MCAO was higher than that observed in the permanent MCAO model. Hydroxyl radical scavenger, MCI-186 significantly suppressed the enhanced fluorescence intensity. This study demonstrated that HPF has a high sensitivity and specificity for the detection of hROS in focal cerebral ischemia as well as in a cellular model of oxidative stress.