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ABSTRACT: Angiomatous meningiomas are rare meningioma subtypes, which are characterized by abundant, well-formed vessels. We encountered two cases of newly diagnosed angiomatous meningiomas exhibiting tumor cells with brown pigments, which were histochemically proven to be iron. In an attempt to understand its pathological significance, we assessed this unusual finding in representatives for each grade of meningiomas and immunoexpression of transferrin receptor (CD71) and the oxidative DNA damage marker, 8-hydroxy-2'-deoxyguanosine (8-OHdG). Iron deposition in the tumor cells was observed in 8/15 (53%) angiomatous meningioma cases, 2/6 (33%) microcystic meningiomas and 2/20 (10%) meningothelial meningiomas, which included clustered microvessels, but not in fibrous, atypical or anaplastic meningiomas (P = 0.001). Cytoplasmic CD71 expression was largely negative in angiomatous meningioma cases, but positive in meningothelial and high-grade meningiomas, suggesting that the transferrin-dependent iron transporter was involved in iron uptake in meningiomas. Nuclear expression of 8-OHdG was observed in ≥50% of the tumor cells in all 15 cases of angiomatous meningioma and was associated with the presence of regressive histopathological findings, such as hyalinized vessels and cystic changes. In addition, the fraction of iron-containing tumor cells was correlated to those expressing 8-OHdG (P = 0.005). Our finding indicates that cytoplasmic iron deposition in tumor cells is characteristic of highly vascularized benign meningiomas and related to increased oxidative DNA damage markers.
Neuropathology 02/2013; · 2.02 Impact Factor
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ABSTRACT: Various degrees of peritumoral brain edema (PTBE) are observed in patients with intracranial meningiomas. Factors affecting the occurrence of PTBE in intracranial meningioma were investigated. PTBE was investigated retrospectively for 110 patients with primary intracranial meningiomas. Predictive factors related to PTBE were analyzed, for example patient age, sex, magnetic resonance imaging features (contrast enhancement, tumor shape, tumor location, tumor volume), angiographical features (tumor stain, pial-cortical arterial supply, venous obstruction), and histopathological features (histological subtypes, mindbomb homolog 1 labeling index (MIB1-LI)). Histological subtypes were classified into World Health Organization (WHO) grade I common type (meningothelial, transitional, fibrous), grade I uncommon type, and grade II and III types. The extent of PTBE was assessed by calculation of the edema index (EI). PTBE was present in 53 cases (48 %). Male sex, heterogeneous enhancement, superficial location, tumor volume (≥10 cm(3)), remarkable tumor stain, pial supply, venous obstruction, malignant pathology, and MIB1-LI ≥4 % were correlated with PTBE in univariate analysis. Pial supply and remarkable tumor stain were correlated with PTBE in multivariate analysis. WHO grade I uncommon type had obviously higher EI than WHO grade I common type, and WHO grade II and III types (P < 0.001). Seven cases with prominently high EI (EI ≥10) were all WHO grade I uncommon type, including angiomatous, microcystic, secretory, and lymphoplasmacyte-rich meningioma. Prominently extensive PTBE might indicate the presence of WHO grade I uncommon type meningioma.
Journal of Neuro-Oncology 10/2012; · 3.21 Impact Factor
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ABSTRACT: 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<0.01) and induced remyelination (P<0.01) compared with the control groups. Also the inflammatory response was repressed by MVEC transplantation, judging from fewer ED-1-positive activated microglial cells in the MVEC-transplanted group than in the other groups. Elucidation of the mechanisms by which MVECs ameliorate ischemic damage of the white matter may provide important information for the development of effective therapies for white matter ischemia.
Brain research 07/2012; 1469:43-53. · 2.46 Impact Factor
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ABSTRACT: Management of asymptomatic unruptured intracranial aneurysms remains controversial, and recent prospective follow-up studies showed that the rupture rate of small aneurysms is very low. These results are inconsistent with the finding that the majority of ruptured aneurysms in patients with subarachnoid hemorrhage are small.
A Markov model was constructed to simulate the natural history of intracranial aneurysms. All epidemiological and statistical data obtained from the Portal Site of Official Statistics of Japan (e-Stat) were adjusted to the standardized age distribution. From the selected data of aneurysm formation, the prevalence of unruptured aneurysms was estimated as 1.45% and the incidence of subarachnoid hemorrhage calculated to be 19.7/100 000/year in the whole standardized population.
The function for rupture rate constant with time was first analyzed. Selected values for annual rupture rates of 0.3%, 0.5%, 0.7%, and 1.0% showed inconsistencies in the relationship between the prevalence of unruptured aneurysm and the incidence of subarachnoid hemorrhage. Next, the function for a short period of high risk followed by a long period of low risk was considered. Annual rupture rates of 0.5%, 0.7%, and 1.0% indicated epidemiological compatibility with additional early rupture rates of 20%, 15%, and 10%, respectively.
This study suggests that some aneurysms bleed shortly after formation and thus are rarely detected as unruptured aneurysms. Most aneurysms without early rupture remain stable for the remainder of life through some healing process, and prophylactic treatment for incidentally identified small unruptured aneurysms has no rationale.
Stroke 12/2011; 42(12):3376-81. · 5.73 Impact Factor
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Acta Neurochirurgica 08/2011; 153(10):1995-6. · 1.52 Impact Factor
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ABSTRACT: Pilomyxoid astrocytoma (PMA) is a newly identified variant of pilocytic astrocytoma (PA). We report three cases of PMA with comparison to seven cases of PA in terms of their clinicopathological features. The three cases occurred at the ages of 2, 36 and 6 years, and their tumors were located in the left basal ganglia, the pineal gland, and the cerebellum, respectively. They were diagnosed PMA by surgical specimens that showed a characteristic monomorphous architecture with an angiocentric growth pattern and myxoid background. One patient developed localized relapse at 6 months after the surgery, but the other patients remained alive without tumor progression more than 5 years after treatment. In analysis of the immunohistochemical association in PMA and PA, no specific staining was found to be useful for differential diagnosis of PMA from PA. The expression of biomarkers including O-6-methylguanine-DNA methyltransferase, p53, MIB-1, and EGF receptor neither distinguished PMA from PA nor correlated with outcome. But almost all PMA and PA that demonstrated prominent positivity for nestin showed a high MIB-1 labelling index (LI), and four of these five patients suffered a relapse in the early phase. These results suggest that immunohistochemical expression of nestin and MIB-1 LI may correlate with the aggressiveness of the tumor in PA and PMA.
Neuropathology 04/2011; 31(2):152-7. · 2.02 Impact Factor
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ABSTRACT: 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.
Brain research 03/2011; 1397:55-65. · 2.46 Impact Factor
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Emi Ishida,
Masanobu Yamada,
Kazuhiko Horiguchi,
Ryo Taguchi,
Atsushi Ozawa,
Nobuyuki Shibusawa,
Koshi Hashimoto,
Tetsuro Satoh,
Sachiko Yoshida,
Yoshiki Tanaka,
Machiko Yokota,
Masahiko Tosaka,
Junko Hirato,
Shozo Yamada, Yuhei Yoshimoto,
Masatomo Mori
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ABSTRACT: Tumors in multiple endocrine neoplasia type 1 (MEN1) are generally benign. Since information on the pathogenesis of MEN1 in malignant cases is limited, we conducted genetic analysis and compared the expression of menin, p27(Kip1)(p27)/CDKN1B and p18(Ink4C)(p18)/CDKN2C with levels in benign cases. We describe the case of a 56 year-old male with an atypical prolactinoma and malignant pancreatic neuroenocrine tumor. At age 50, he had undergone transsphenoidal surgery to remove a prolactinoma. However, the tumor relapsed twice. Histological analysis of the recurrent prolactinoma revealed the presence of prolactin, a high MIB-1 index (32.1 %), p53-positive cells (0.2%), and an unusual association with FSH-positive cells. A few years later, he was also found to have a non-functioning pancreatic tumor with probable metastasis to the extradullar region. The metastatic region tested positive for chromogranin and CD56, and negative for prolactin, with 1.2 % of cells p53-positive. Although genetic analyses of the MEN1, p27, and p18 genes demonstrated no mutation, numbers of menin, p27 and p18 immuno-positive cells were significantly down-regulated in the recurrent prolactinoma, but that of p18 was intact in the metastatic region. Furthermore, MEN1 and p27 mRNA levels of the recurrent prolactinoma were down-regulated, particularly the MEN1 mRNA level, compared to levels in 10 cases of benign prolactinoma, while the p18 mRNA level was similar to that of normal pituitary. The tumor in this case may be a subtype of MEN1 showing more aggressive and malignant features probably induced by low levels of menin and p27.
Endocrine Journal 03/2011; 58(4):287-96. · 2.03 Impact Factor
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ABSTRACT: Ruptured aneurysms arising from non-branching sites of the internal carotid artery (ICA) are often difficult to treat by neck clipping or endosaccular coiling. We discuss the feasibility of simple endovascular ICA ligation or trapping to treat aneurysms.
Data from eleven patients were retrospectively analyzed regarding Hunt and Hess grade on admission, angiographic collateral capacities during digital carotid compression, results of balloon test occlusion of the ipsilateral ICA, type of treatment, and Glasgow outcome scale at discharge.
First endovascular treatments were performed by day 5 in four cases. Two patients with good clinical grade and good collateral capacity underwent endovascular ICA trapping in the acute stage and showed good outcomes. Two patients displaying poor clinical grade but good collaterals underwent endosaccular embolization. These aneurysms recurred later and the ICAs were trapped by coils in the chronic stage. Four cases underwent first endovascular treatments in the chronic stage. Three patients with good collaterals underwent endovascular ICA trapping or ligation and showed favorable outcomes.
Seven of eleven patients could be treated by endovascular ICA trapping or ligation, which offers a simple, safe method for ruptured ICA trunk aneurysms, if collateral capacity is good and neurological condition is not serious.
Clinical neurology and neurosurgery 01/2011; 113(4):285-8. · 1.30 Impact Factor
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ABSTRACT: Several kinds of unusual cells have been pathologically identified in epileptic patients. CD34-positive, nestin-positive and tau-positive cells are some of them. However, no reports have investigated the significance of these cells. We examined 14 cases of seizure-associated glioneuronal lesions to investigate the incidences and distributions of these cells and the association between their incidence and clinical parameters. CD34-positive and nestin-positive cells were seen in 43% and 50% of cases, respectively. In the regions with structural anomalies, there were increased numbers of CD34-positive cells and nestin-positive cells, but they were identified as different cells. Both examinations showed many abnormal processes in oligodendroglial-like cells with round nuclei. In contrast, few reactive astrocytes that demonstrated immunoreactivity for glial fibrillary acidic protein were found in this area. Tau accumulation was present in 37% of cases. There was no correspondence with the regions showing increasing numbers of nestin or CD34-positive cells. There were no significant associations between epileptic clinical parameters and the incidences of the abovementioned immunopositive cells. CD34-positive cells and nestin-positive cells are found as frequently as balloon cells and are associated with abnormal reconstitution of the cortex. These findings support the assertion that increases in the numbers of these cells might contribute to promoting epilepsy. In addition, these immunopositive cells are valuable findings for the pathological identification of epileptogenic lesions.
Neuropathology 01/2011; 31(5):468-75. · 2.02 Impact Factor
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ABSTRACT: A 54-year-old female presented with a very rare intraosseous neurofibroma of the frontal bone manifesting as forehead bulging. Skull radiography showed a radiolucent round lesion. Magnetic resonance imaging showed a mass lesion expanding from the frontal bone diploic layer to the epidural space. Fluorodeoxyglucose positron emission tomography and thallium-201 single photon emission computed tomography findings indicated tumor malignancy. The tumor was resected, and the histological diagnosis was benign intraosseous neurofibroma. Intraosseous neurofibroma usually occurs in the mandible. The origin of the present case may have been a peripheral nerve in the diploic vascular tissue.
Neurologia medico-chirurgica 01/2010; 50(8):683-6. · 0.61 Impact Factor
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ABSTRACT: The clarification of mechanisms that negatively regulate the invasive behavior of human glioma cells is of great importance in order to find new methods of treatment. In this study, we have focused on the negative regulation of lysophosphatidic acid (LPA)-induced migration in glioma cells. Using small interference RNA and dominant-negative gene strategies in addition to pharmacological tools, we found that isoproterenol (ISO) and sphingosine-1-phosphate (S1P) negatively but differently regulate the LPA-induced migration. ISO-induced suppression of the migration of glioma cells occurs via beta(2)-adrenergic receptor/cAMP/Epac/Rap1B/inhibition of Rac, whereas S1P has been shown to suppress the migration of the cells through S1P(2) receptor/Rho-mediated down-regulation of Rac1. The expression of tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is required for the inhibitory ISO-induced and Rap1B-mediated actions on the migration, Rac1 activation, and Akt activation in response to LPA. Thus, the PTEN-mediated down-regulation of phosphatidylinositol 3-kinase activity may be involved in the regulation of Rap1B-dependent inhibition of Rac1 activity. These findings suggest that there are at least two distinct inhibitory pathways, which are mediated by the S1P(2) receptor and beta(2)-adrenergic receptor, to control the migratory, hence invasive, behavior of glioma cells.
Molecular biology of the cell 10/2009; 20(24):5156-65. · 5.98 Impact Factor
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ABSTRACT: 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.
Journal of Biological Chemistry 10/2009; 285(1):667-74. · 4.77 Impact Factor
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Mitsunobu Nakamura,
Hideaki Imai,
Kenjiro Konno,
Chisato Kubota,
Koji Seki,
Sandra Puentes,
Ahmad Faried,
Hideaki Yokoo,
Hidekazu Hata, Yuhei Yoshimoto,
Nobuhito Saito
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ABSTRACT: 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.
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.
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.
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.
Journal of Neurosurgery Pediatrics 07/2009; 3(6):488-95. · 1.53 Impact Factor
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ABSTRACT: Several major randomized controlled trials of carotid endarterectomy (CEA) in patients with both symptomatic and asymptomatic carotid artery stenosis have addressed the net effects of CEA on the risk of stroke. However, because the risk of stroke among patients with asymptomatic carotid stenosis is relatively low, whether to treat their stenosis with CEA remains an important public health issue.
The authors constructed a Markov model to evaluate the effectiveness of CEA. In modeling 4 health states, the probability of transition to another state was estimated using data from major randomized controlled trials. Adopting 3 comorbidity index values for baseline analyses, the authors expressed outcomes in terms of the expected number of quality-adjusted life years (QALYs) for a hypothetical cohort undergoing CEA and another without treatment.
In the authors' baseline analysis, CEA for asymptomatic stenosis yielded a very small benefit (0.07 QALY) for 70-year-old, normal-risk CEA candidates. Benefits decreased further, often becoming negative, as patient age, surgical risk, or comorbidity index increased. In patients with symptomatic stenosis, CEA was always more effective than conservative management, even considering variables such as comorbidities limiting life expectancy, advanced age, and increased perioperative risk.
Carotid endarterectomy for severe carotid stenosis consistently and significantly benefits patients with recent symptoms. However, surgery for asymptomatic stenosis appears justified only in carefully selected conditions: low treatment risks in relatively young individuals without any comorbidities.
Journal of Neurosurgery 06/2009; 111(5):970-7. · 2.96 Impact Factor
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ABSTRACT: A previously healthy 22-year-old man presented with thoracic outlet syndrome manifesting as Raynaud's phenomenon in the left hand and embolic occlusion of the basilar artery. Three-dimensional computed tomography angiography showed that the left subclavian artery was occluded as it passed over the abnormal first rib. Retrograde propagation of the thrombus from the site of arterial occlusion and/or reflux of embolic material was suspected. Medical therapy was started. The patient underwent resection of the anomalous rib. Postoperative angiography demonstrated that the subclavian artery was recanalized with almost normal distal flow. The basilar artery was also recanalized. Thoracic outlet syndrome due to a first rib anomaly may cause stroke.
Neurologia medico-chirurgica 09/2008; 48(8):355-8. · 0.61 Impact Factor
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ABSTRACT: 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.
No shinkei geka. Neurological surgery 09/2008; 36(8):703-7. · 0.13 Impact Factor
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ABSTRACT: Sphingosine 1-phosphate (S1P) induced the inhibition of glioma cell migration. Here, we characterized the signaling mechanisms involved in the inhibitory action by S1P. In human GNS-3314 glioblastoma cells, the S1P-induced inhibition of cell migration was associated with activation of RhoA and suppression of Rac1. The inhibitory action of S1P was recovered by a small interference RNA specific to S1P(2) receptor, a carboxyl-terminal region of Galpha12 or Galpha13, an RGS domain of p115RhoGEF, and a dominant-negative mutant of RhoA. The inhibitory action of S1P through S1P(2) receptors was also observed in both U87MG glioblastoma and 1321N1 astrocytoma cells, which have no protein expression of a phosphatase and tensin homolog deleted on chromosome 10 (PTEN). These results suggest that S1P(2) receptors/G(12/13)-proteins/Rho signaling pathways mediate S1P-induced inhibition of glioma cell migration. However, PTEN, recently postulated as an indispensable molecule for the inhibition of cell migration, may not be critical for the S1P(2) receptor-mediated action in glioma cells.
Biochemical and Biophysical Research Communications 03/2008; 366(4):963-8. · 2.48 Impact Factor
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Yukitaka Tanaka,
Hideaki Imai,
Kenjiro Konno,
Takaaki Miyagishima,
Chisato Kubota,
Sandra Puentes,
Takeo Aoki,
Hidekazu Hata,
Kuniaki Takata, Yuhei Yoshimoto,
Nobuhito Saito
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ABSTRACT: 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.
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.
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<0.001, maximum score 25) with motor deficit scores of 3.4 (95% CI, 2.9 to 4.0) and 0.0 (CI, 0.0 to 0.0), respectively (P<0.001, maximum score 9). Histology revealed that the internal capsule lesion expands gradually from acute to chronic phases.
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.
Stroke 02/2008; 39(1):205-12. · 5.73 Impact Factor
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ABSTRACT: Sphingosine 1-phosphate (S1P) is accumulated in lipoproteins, especially high-density lipoprotein (HDL), in plasma. However, it remains uncharacterized how extracellular S1P is produced in the CNS. The treatment of rat astrocytes with retinoic acid and dibutyryl cAMP, which induce apolipoprotein E (apoE) synthesis and HDL-like lipoprotein formation, stimulated extracellular S1P accumulation in the presence of its precursor sphingosine. The released S1P was present together with apoE particles in the HDL fraction. S1P release from astrocytes was inhibited by the treatment of the cells with glybenclamide or small interfering RNAs specific to ATP-binding cassette transporter A1 (ABCA1). Astrocytes from Abca1-/- mice also showed impairment of retinoic acid/dibutyryl cAMP-induced S1P release in association with the blockage of HDL-like lipoprotein formation. However, the formation of either apoE or lipoprotein itself was not sufficient, and additional up-regulation of ABCA1 was requisite to stimulate S1P release. We conclude that the S1P release from astrocytes is coupled with lipoprotein formation through ABCA1.
Journal of Neurochemistry 11/2007; 103(6):2610-9. · 4.06 Impact Factor
