Biomedical subjects

Satoshi Kuroda

Publications and source records attributed to Satoshi Kuroda.

At least 19 recordsLinked to original sources

PubMed2006

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

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

Animals↗

PubMed2006

The effects of neuronal induction on gene expression profile in bone marrow stromal cells (BMSC)--a preliminary study using microarray analysis.

Bone marrow stromal cells (BMSC) have been anticipated as a donor for cell type for transplantation therapy in various neurological disorders. However, their neurogenic capacity still remains undetermined. In this study, we aimed to clarify whether in vitro chemical treatment promotes their neuronal differentiation on the level of gene expression. Mice BMSC were cultured with medium supplemented with DMSO, retinoic acid, and basic fibroblast growth factor, and their morphology and expression of neuronal markers were evaluated. Subsequently, using microarray and RT-PCR techniques, the treatment-induced changes in the gene expression profile were analyzed. After exposure to the medium, the BMSC simulated a neuron-like appearance and increased their immunoreactivity for nestin and Tuj-1. Microarray analysis revealed that the BMSC per se express the multilineage cellular genes, including those associated with the neuron. Chemical treatment significantly decreased the expression of genes related to mesenchymal cells and increased the expression of 5 neuron-associated genes. Microarray and RT-PCR analyses also demonstrated that the BMSC express the genes for several growth factors including NGF-beta and BDNF, indicating their therapeutic role in protecting the injured central nervous system. The present results suggest that at least a certain subpopulation of the BMSC have the potential to alter their gene expression profile in response to the surrounding environment and may possibly protect the host tissue by secreting neuroprotective factors.

Animals↗

PubMed2006

How does spontaneous hemostasis occur in ruptured cerebral aneurysms? Preliminary investigation on 247 clipping surgeries.

BACKGROUND: Rupture of cerebral aneurysms results in subarachnoid hemorrhage. In many cases, bleeding from aneurysms spontaneously arrests. Although bleeding from cerebral aneurysms has been reported to arrest from outside, bleeding from some aneurysms can arrest in different ways. METHODS: Between April 2002 and March 2004, we prospectively investigated mechanisms of spontaneous hemostasis in ruptured aneurysms by macroscopic examination when performing craniotomy and clipping surgeries. RESULTS: Hemostatic mechanisms were investigated in 247 patients with ruptured aneurysm (77 men, 170 women; age range, 25-95 years). Hemostatic mechanisms were divided into 3 different patterns. In the most common pattern (79.4%), the surface of the aneurysm rupture point was sealed from the outside by a platelet plug or fibrin net (outside-arrest pattern). In some aneurysms (10.1%), a thrombus or platelet plug was attached to the rupture point from inside the aneurysm (inside-arrest pattern). In a very small number of aneurysms (1.6%), a naked thrombus covered the hole made on the arterial wall or small remnant of the aneurysmal dome (bursting pattern) The mechanism remained unclear in the remaining 8.9% of aneurysms. Multivariate analysis revealed that alert consciousness on admission (WFNS grade I) significantly associated with usual hemostasis (outside arrest pattern: OR, 3.8; 95% CI, 1.4-10.0; P = .008). Borderline association with usual hemostasis was found in aneurysms with a size of 5 or smaller than 5 mm (OR, 2.6; 95% CI, 0.99-7.1; P = .052). CONCLUSIONS: The present preliminary study revealed that arrest of bleeding from a ruptured cerebral aneurysm does not always occur from outside the aneurysm. Unusual mechanisms of hemostasis are seen in approximately 12% of ruptured aneurysm. The outside-arrest-pattern aneurysm was more common for smaller aneurysms, and these patients tended to be of better grade. Further studies are necessary to explore the mechanism of hemostasis for ruptured cerebral aneurysms.

Adult↗

PubMed2006

Bone marrow stromal cell transplantation preserves gammaaminobutyric acid receptor function in the injured spinal cord.

A surprising shortage of information surrounds the mechanisms by which bone marrow stromal cells (BMSC) restore lost neurologic functions when transplanted into the damaged central nervous system. In the present study, we sought to elucidate whether BMSCs express the neuron-specific gamma-aminobutyric acid (GABA) receptor when transplanted into injured spinal cord. To examine this, we harvested and cultured rat femoral BMSCs. We then subjected Sprague-Dawley rats to thoracic spinal cord injury (SCI) with a pneumatic impact device. Fluorescence-labeled BMSCs (n = 7) were transplanted stereotactically or the vehicle in which these cells were cultured (n = 4) was introduced stereotactically into the rostral site of SCI at 7 days after injury. We evaluated GABA receptor function by measuring the binding potential for 125I-iomazenil (125I-IMZ) through in vitro autoradiography at 4 weeks after BMSC transplantation and simultaneously examined the fate of the transplanted BMSCs by immunocytochemistry. We found that the transplanted BMSC migrated toward the core of the injury and were densely distributed in the marginal region at 4 weeks after transplantation. BMSC transplantation significantly increased the binding potential for 125I-IMZ (p = 0.0376) and increased the number of GABA receptor-positive cells (p = 0.0077) in the marginal region of the injury site. Some of the transplanted BMSCs were positive for microtubule-associated protein-2 and the alpha1 subunit of GABA(A) receptor in the region of injury. These findings suggest that BMSCs have the potential to support the survival of neurons in the marginal region of SCI and can partly differentiate into neurons, regenerating spinal cord tissue at the site of injury.

Animals↗

PubMed2006

Simultaneous superficial temporal artery to middle cerebral or anterior cerebral artery bypass with pan-synangiosis for Moyamoya disease covering both anterior and middle cerebral artery territories.

Some patients with moyamoya disease treated by conventional surgical procedures may develop postoperative refractory ischemia and perioperative cerebral infarction in the anterior cerebral artery (ACA) territory. We present a novel operative procedure for moyamoya disease to avoid the risk of ischemia in the ACA territory, which consists of simultaneous superficial temporal artery (STA) to middle cerebral artery (MCA) or ACA bypass with pan-synangiosis, encephalo-duro-arterio-myo-synangiosis for the lateral frontal and temporal areas, and encephalo-galeo-arterio-synangiosis for the medial frontal area. This procedure can establish direct bypass to the ACA territory at the first intervention. Simultaneous STA-MCA and STA-ACA bypasses with pan-synangiosis is suitable for patients with moyamoya disease associated with severely impaired perfusion of the ACA territory requiring direct bypass surgery.

Adolescent↗

PubMed2006

Improved expression of gamma-aminobutyric acid receptor in mice with cerebral infarct and transplanted bone marrow stromal cells: an autoradiographic and histologic analysis.

UNLABELLED: Recent studies have indicated that bone marrow stromal cells (BMSC) have the potential to improve neurologic function when transplanted into animal models of central nervous system disorders. However, how the transplanted BMSC restore the lost neurologic function is not clear. In the present study, therefore, we aimed to elucidate whether BMSC express the neuron-specific gamma-aminobutyric acid (GABA) receptor when transplanted into brain that has been subjected to cerebral infarction. METHODS: The BMSC were harvested from green fluorescent protein-transgenic mice and were cultured. The mice were subjected to permanent middle cerebral artery occlusion. The BMSC or vehicle was transplanted into the ipsilateral striatum 7 d after the insult. Using autoradiography and fluorescence immunohistochemistry, we evaluated the binding of 125I-iomazenil and the expression of GABA receptor protein in and around the cerebral infarct 4 wk after transplantation. RESULTS: Binding of 125I-iomazenil was significantly higher in the periinfarct neocortex in the BMSC-transplanted animals than in the vehicle-transplanted animals. Likewise, the number of the GABAA receptor-positive cells was significantly higher in the periinfarct neocortex in the BMSC-transplanted animals than in the vehicle-transplanted animals. A certain subpopulation of the transplanted BMSC expressed a neuron-specific marker, microtubule-associated protein 2, and the marker protein specific for GABAA receptor in the periinfarct area. CONCLUSION: These findings suggest that BMSC may contribute to neural tissue regeneration through migrating toward the periinfarct area and acquiring the neuron-specific receptor function.

Animals↗

PubMed2006

[Repeated, reversible MR angiographic findings in pediatric moyamoya disease: case report].

The authors report a 6-year-old girl presented with headache and transient ischemic attack due to moyamoya disease. MR angiography (MRA) revealed that her symptoms were closely related to reversible deterioration of stenosis in the left middle cerebral artery (MCA). Deterioration of stenosis led to a decreased flow signal in the distal branches of the left MCA. MRA could also detect reversible stenotic changes in the right MCA, although she did not develop any neurological symptom. Although precise mechanism of reversible MR angiographic findings is still unknown, the phenomenon may play an important role in disease progression in pediatric patients with moyamoya disease.

Child↗

PubMed2006

[CNS sarcoidosis presenting with intracerebral hemorrhage: case report].

Sarcoidosis is a systemic, chronic inflammatory disease characterized by non-caseating epithelioid granuloma. It is well known that the central nervous system (CNS) is also involved in about 5% of patients with systemic sarcoidosis. Although CNS sarcoidosis presents with various neurological manifestations, intracerebral bleeding is quite rare. In this report, we describe a case in which a patient suffered from intracerebral hemorrhagic due to CNS sarcoidosis. A 57-year-old male who had been diagnosed as having systemic sarcoidosis was admitted to our hospital due to status epilepticus. Plain CT scan showed a subcortical hematoma in the left marginal gyrus. Serial MR imaging revealed that an enhanced mass in the overlying cortex had gradually increased its size. Subsequently, the enhanced mass and hematoma were totally removed, using a navigation system. Pathological examination revealed typical findings of sarcoidosis. We discuss the mechanism of intracerebral bleeding due to CNS sarcoidosis in this report.

Brain↗

PubMed2006

[Motor cortex stimulation for post-stroke pain using neuronavigation and evoked potentials: report of 3 cases].

Although motor cortex stimulation (MCS) has been accepted as an effective therapeutic option for central pain, the efficacy of MCS widely varies among previous reports. In this report, we describe our recent trial for successful MCS in 3 patients with central pain due to cerebral stroke. Medical treatments were transiently effective, but gradually became ineffective in all of the cases. During surgery, the appropriate cortical target was determined by using neuronavigation, somatosensory evoked potential (SEP), and motor evoked potential (MEP). A flat, four-plate electrode was positioned on the dura mater parallel to the motor cortex. After surgery, pain almost resolved in 2 of 3 patients and markedly improved in another. The pain relief depended on their motor function. These findings strongly suggest that both patient selection and intraoperative monitoring for targeting the motor cortex are quite important for successful MCS, although further studies were essential.

Aged↗

PubMed2006

[A novel method of dural repair using polyglycolic acid non-woven fabric and fibrin glue: clinical results of 140 cases].

This paper presents a report based on the results obtained from clinical applications of a biocompatible dural substitute made of polyglycolic acid non-woven fabric and fibrin glue. The cases subjected to this study were the ones needing reconstruction of dura mater which had become defective due to injury or brain tumor and the ones in which primary suture of the dura mater was considered to be too difficult or inadequate with ordinary methods. The dural substitute was used in 140 cases during the period between June, 2001 and July, 2005. The operations were performed using the supratentorial approach in 66 cases and infratentorial approach in 74 cases. Among these procedures, 39 cases were indicated for microvascular decompression, the commonest operation performed, then cranial base surgery in 27 cases and tumor resection in 24 cases, and so on. Lumber spinal fluid drainage or re-operation was required in 3 cases (2.1%) due to formation of post-operative cerebrospinal fluid leakage or subcutaneous accumulation of cerebrospinal fluid. With the dural substitute no infection was observed as a complication in any of the cases. Among the 140 cases presented this time, 27 cases were cranial base surgery and 74 cases were performed, using the infratentorial approach. Nevertheless, the study showed that the closing ability of the dural substitute was adequate even in actual clinical settings it is reported above that the incidence rate of post-operative cerebrospinal fluid leakage or subcutaneous accumulation of cerebrospinal fluid which require additional intervention was only 2.1%.

Adult↗

PubMed2005

Cerebral oxygen metabolism and neuronal integrity in patients with impaired vasoreactivity attributable to occlusive carotid artery disease.

BACKGROUND AND PURPOSE: It is still unclear that impaired cerebrovascular reactivity (CVR) to acetazolamide is comparable to elevated oxygen extraction fraction (OEF) on positron emission tomography (PET) in patients with occlusive carotid diseases. Therefore, in this study, the authors aimed to clarify whether OEF is elevated in all patients with reduced cerebral blood flow (CBF) and CVR (type 3) on single photon emission computed tomography (SPECT), and, if not, to specify the underlying pathophysiology of type 3 but normal OEF. METHODS: This study included 46 patients who had decreased CBF and CVR on N-isopropyl-p-(123)I-iodoamphetamine SPECT in the ipsilateral middle cerebral artery area attributable to occlusive carotid diseases. Hemodynamic and metabolism parameters were determined in all patients by (15)O-gas PET, and neuronal integrity was evaluated in 19 patients using 11C-flumazenil (FMZ) PET. RESULTS: OEF was significantly elevated in 20 (43.5%) of 46 type 3 patients. Another 26 type 3 patients had normal OEF. Regression analysis showed that OEF significantly correlated with cerebral metabolic rate for oxygen and 11C-FMZ binding potential but not with other parameters. Subcortical infarction had no significant effect on OEF values. CONCLUSIONS: The results strongly suggest that type 3 patients with reduced CBF and CVR may be divided into 2 pathophysiologically different subgroups: misery perfusion attributable to hemodynamic compromise and matched hypometabolism attributable to incomplete infarction. Type 3 but normal OEF may represent a transition stage from misery perfusion to matched hypometabolism.

Aged↗

PubMed2005

Do bone marrow stromal cells proliferate after transplantation into mice cerebral infarct?--a double labeling study.

The present study was aimed to clarify the proliferation capacity of the bone marrow stromal cells (BMSC) transplanted into the brain. The BMSC were harvested from green fluorescence protein (GFP)-transgenic mice, grown to the confluency and passed three times. They were labeled by co-culture with Ferucarbotran, a superparamagnetic iron oxide (SPIO) agent. The proportions of the SPIO-positive cells were evaluated from P3 to P7, using Turnbull blue staining. The GFP-BMSC labeled by Ferucarbotran were transplanted into the ipsilateral striatum of the mice brain subjected to permanent focal ischemia at 7 days after the insult. The distribution and differentiation of GFP- and SPIO-positive cells in the brain were studied 3 months after transplantation, using immunohistochemistry and Turnbull blue staining. As the results, the proportions of the SPIO-positive cells gradually decreased from 93.6% at P3 to 6.5% at P7. Fluorescence immunohistochemistry revealed that the GFP-positive cells were widely distributed around infarct and partially expressed MAP2 and NeuN 3 months after transplantation. However, only a smaller number of SPIO-positive cells could be detected on Turnbull blue staining. The ratio of the SPIO- to GFP-positive cells was approximately 2.7%. The results strongly suggest that the BMSC repeat proliferation many times, migrate into the lesion, and partially express the neuronal phenotype in the host brain during 3 months after transplantation. The double labeling technique would be valuable to prove the proliferation of the transplanted cells in the host tissue because GFP gene and SPIO nanoparticles have different inheritance characteristics.

Animals↗

PubMed2005

Clinical features of familial moyamoya disease.

OBJECTS: This study aims to clarify the genetic background of moyamoya disease by comparing clinical features between familial and sporadic cases to reveal the responsible genes for familial moyamoya disease. METHODS: This study included 155 Japanese patients with moyamoya disease, which included 24 familial cases (10 family pedigrees) and 131 sporadic cases. Clinical features were compared between the familial and sporadic cases. RESULTS AND CONCLUSION: A female preponderance was significantly more prominent in the familial than in the sporadic group (P=0.0421). Mean age at onset was significantly lower in familial than in sporadic cases (P=0.004). In eight parent-offspring pairs, mean age at onset was significantly lower in the second than in the first generation (P<0.0001). These results suggest that familial moyamoya disease is associated with genetic anticipation and female predominance and that a genetic analysis study focused on expanded triplet repeats may clarify the pathogenesis of the disease.

Adolescent↗

PubMed2005

Incidence and clinical features of disease progression in adult moyamoya disease.

BACKGROUND AND PURPOSE: The progression of occlusive lesions in the major intracranial arteries was believed to be very rare in adult patients with moyamoya disease. The present study aims to clarify the incidence and clinical features of disease progression in adult moyamoya disease. METHODS: For the past 15 years, 120 adult Japanese patients were diagnosed with moyamoya disease. Of these, 63 patients were enrolled in this historical prospective cohort study on a total of 86 nonoperated hemispheres. All were followed up with a mean period of 73.6 months. MRI and magnetic resonance angiography were repeated every 6 to 12 months, and cerebral angiography was performed when disease progression was suspected on MRI and magnetic resonance angiography. RESULTS: Disease progression occurred in 15 of 86 nonoperated hemispheres (17.4% per hemisphere) or in 15 of 63 patients (23.8% per patient) during the follow-up period. Occlusive arterial lesions progressed in both anterior and posterior circulations, in both symptomatic and asymptomatic patients, and in both bilateral and unilateral types. Eight of 15 patients developed ischemic or hemorrhagic events in relation to disease progression. Multivariate analysis revealed that the odds ratio conferred by a male patient was 0.20 (95% CI, 0.04 to 0.97). CONCLUSIONS: The incidence of disease progression in adult moyamoya disease is much higher than recognized before, and female patients may be at higher risk for it than male patients. Careful follow-up would be essential to prevent additional stroke occurrence in medically treated adult patients with moyamoya disease, even if they are asymptomatic or are diagnosed as having unilateral moyamoya disease.

Adult↗

PubMed2005

Novel magnetic resonance angiography stage grading for moyamoya disease.

BACKGROUND: Magnetic resonance angiography (MRA) has been acknowledged as a noninvasive diagnostic modality for moyamoya disease. However, in terms of staging of moyamoya disease, conventional angiography is still the gold standard. Therefore, the purpose of this study was to establish MRA grades for moyamoya disease as an alternative to conventional angiography. METHODS: Twenty-two patients (44 sides) with moyamoya disease diagnosed by conventional angiography were evaluated by MRA during the past 5 years. MRA scores were assigned based on the severity of occlusive changes of the internal carotid artery, the horizontal portion of the middle cerebral artery, the anterior and the posterior cerebral arteries and the signals of the distal branches of these arteries. Total points ranged from 0 (normal) to 10 (most severe). RESULTS: MRA scores (0-10) were significantly consistent with the conventional angiographic staging. Four grades based on this novel MRA scores correlated well with Suzuki's stages, with high sensitivity and specificity. CONCLUSIONS: These novel MRA grades can be a reliable alternative to conventional staging. By employing these novel MRA grades, the use of conventional angiography can be avoided for the purpose of evaluation of the stages of moyamoya disease.

Adolescent↗

PubMed2005

Comparison of imaging modalities for the accurate delineation of arteriovenous malformation, with reference to stereotactic radiosurgery.

PURPOSE: To investigate the discrepancy between the arteriovenous malformations seen on magnetic resonance angiography (MRA) and on stereotactic digital subtracted angiography (DSA). METHODS AND MATERIALS: The target volume on stereotactic DSA (V(DSA)) and the target volume on MRA (V(MRA)) were separately delineated in 28 intracranial arteriovenous malformations. The coordinates of the center and the outer edges of V(DSA) and V(MRA) were calculated and used for the analyses. RESULTS: The standard deviations (mean value) of the displacement of centers of V(MRA) from V(DSA) were 2.67 mm (-1.82 mm) in the left-right direction, 3.23 mm (-0.08 mm) in the anterior-posterior direction, and 2.16 mm (0.91 mm) in the craniocaudal direction. V(MRA) covered less than 80% of V(DSA) in any dimensions in 9 cases (32%), although no significant difference was seen in the target volume between each method, with a mean value of 11.9 cc for V(DSA) and 12.3 cc for V(MRA) (p = 0.948). CONCLUSION: The shift of centers between each modality is not negligible. Considering no significant difference between V(DSA) and V(MRA), but inadequate coverage of the V(DSA) by V(MRA), it is reasonable to consider that the target on MRA might include the feeding artery and draining vein and possibly miss a portion of the nidus.

Adolescent↗

PubMed2005

Neuroprotective effect of a heat shock protein inducer, geranylgeranylacetone in permanent focal cerebral ischemia.

Previous studies have strongly suggested that heat shock protein 70 (HSP70) has protective effects in ischemia/reperfusion in tissues such as brain, heart, and liver. This study was performed to assess the efficacy of the HSP70 inducer geranylgeranylacetone (GGA) in experiments involving permanent middle cerebral artery (MCA) occlusion. Male Balb/c mice were subjected to permanent MCA occlusion by direct occlusion through small craniectomy. Vehicle or GGA (200 or 1000 mg/kg) was injected intraperitoneally 1 h prior to the onset of ischemia. Infarct volumes were evaluated at 24 h of ischemia by using 2,3,5-triphenyltetrazolium chloride (TTC) staining. The effect of GGA on the induction of HSP70 was studied at 3 h after ischemia with fluorescence immunocytochemistry. The percentage of infarct volume in the control mice (n=10) was 23.0+/-4.0% (mean+/-SD) of the contralateral hemisphere, while those in the treated groups were 22.6+/-7.3% (200 mg/kg group; n=5, P>0.05) and 15.7+/-3.8% (1000 mg/kg group; n=5, P<0.05). Pretreatments with 1000 mg/kg of GGA enhanced the ischemia-related induction of HSP in the neurons and astrocytes in the boundary zone of infarct. The results demonstrate that GGA significantly reduces infarct volume due to permanent MCA occlusion when given 1 h prior to the induction of ischemia.

Animals↗

PubMed2005

In vivo fluorescence tracking of bone marrow stromal cells transplanted into a pneumatic injury model of rat spinal cord.

Recent experimental studies have shown that bone marrow stromal cells (BMSC) differentiate into neural cells and reduce neurological deficits when transplanted into traumatized spinal cord. These findings have been derived primarily from histological analyses. We conducted a study directed chiefly at developing a non-invasive system for tracking BMSC transplanted into the spinal cord of living animals. In this study, we induced spinal cord injury (SCI) in rats with a pneumatic device. BMSC were harvested from transgenic mice expressing green fluorescence protein (BMSC-GFP), and were transplanted stereotactically into a control group of rats without SCI (n = 6) and a group with SCI (n = 3). At 2 and 4 weeks after transplantation, the dura mater was exposed and green fluorescence derived from the transplanted BMSC-GFP was observed. The distribution and differentiation of the transplanted cells were subsequently evaluated with immunohistochemistry. Green fluorescence could be detected around the transplantation site in three of six of the control rats. In all three rats subjected to SCI, green fluorescence was shown to spread from the site of BMSC-GFP injection toward the injury site, suggesting that the transplanted cells had migrated toward the lesion within the 4-week post-transplantation period. Histological evaluation suggested that the detected green fluorescence was emitted by cells that had distributed in the dorsal white matter, and demonstrated that some of the transplanted cells expressed neuronal or astrocytic markers. These results suggest the possibility of tracking BMSC transplanted into the spinal cord in living animals. Such noninvasive bioimaging techniques would be valuable for monitoring the fate of these transplanted cells and assessing the safety and efficacy of their transplantation.

Animals↗