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Yasuhiro Kumai

Publications and source records attributed to Yasuhiro Kumai.

12 recordsLinked to original sources
PubMed2006

Postischemic gene transfer of soluble Flt-1 protects against brain ischemia with marked attenuation of blood-brain barrier permeability.

Brain edema is a major and often mortal complication of brain ischemia. Vascular endothelial growth factor (VEGF) is also known as a potent vascular permeability factor and may play detrimental roles at the acute stage of brain infarction. Our goal in this study was to explore protective effects of gene transfer of soluble flt-1 (sFlt-1), a natural inhibitor of VEGF, on focal brain ischemia. Adenoviral vector encoding sFlt-1 or beta-galactosidase as control was injected into the lateral ventricle 90 mins after photochemical distal middle cerebral artery occlusion in male spontaneously hypertensive rats. The transduced sFlt-1 was released to the cerebrospinal fluid from the ventricular wall and significantly increased 6 h, 1 and 7 days after sFlt-1 transfection. One day after brain ischemia, sFlt-1 gene transfer significantly reduced infarct volume (by 35%), brain edema (by 35%), and blood-brain barrier permeability (Evans blue extravasation; by 69%) with diminished phosphorylation of focal adhesion kinase (FAKtyr397 and FAKtyr861) in the ischemic vessels. Seven days after ischemia, sFlt-1 gene transfer also significantly attenuated infarct volume (by 29%) and monocyte/macrophage infiltration (by 27%), although there were no reductions in angiogenesis by sFlt-1 overexpression. These results suggest that sFlt-1 gene therapy targeting brain edema in acute stage of brain ischemia may be useful for brain infarction.

Animals↗
PubMed2005

Transcranial color-coded sonography for vertebrobasilar disorders in end-stage renal disease.

Because vertebrobasilar arterial disorders seem to be common in patients with end-stage renal disease, a neuroradiological evaluation of vertebrobasilar circulation is necessary for patients with possible vertebrobasilar insufficiency. In three patients on maintenance hemodialysis, contrast-enhanced transcranial color-coded real-time sonography (TCCS) through a suboccipital window delineated occlusion of bilateral vertebral arteries with reversal of the basilar artery, reversal of the left vertebral artery mimicking left subclavian steal phenomenon, and dolichoectasia of the basilar artery and bilateral vertebral arteries with signals of turbulent flow. TCCS has several advantages over computed tomographic angiography and magnetic resonance angiography, including the direction of blood flow, handy performance even during hemodialysis, and contrast agent free from nephrotoxicity. Thus, TCCS is useful in the evaluation of intracranial circulation in patients with end-stage renal disease.

Aged↗
PubMed2005

NAD(P)H oxidases in rat basilar arterial endothelial cells.

BACKGROUND AND PURPOSE: Reactive oxygen species (ROS) may play a critical role in the regulation of vascular tone and development of vascular diseases, such as stroke. NAD(P)H oxidase is a major source of ROS in vascular cells, including endothelial cells. It has been considered that Nox2 and Nox4 are exclusively expressed among Nox homologues in the endothelial cells of noncerebral blood vessels. However, the precise molecular identity of the NAD(P)H oxidase in the endothelial cells of the cerebral arteries is not fully understood. We examined the expression of Nox homologues and their activation mechanism in the endothelial cells of the cerebral arteries. METHODS: We isolated and cultured basilar artery endothelial cells (BAECs) of Sprague-Dawley rats. Expression of NAD(P)H oxidase was examined by reverse-transcription-polymerase chain reaction (RT-PCR) and immunohistological staining. RESULTS: RT-PCR disclosed abundant expression of Nox4 with marginal Nox2 in BAEC. In addition, Nox1 was expressed highly both at mRNA and protein levels in BAECs. Immunohistological staining also showed the prominent expression of Nox1 in the endothelial cells of the basilar artery. With respect to the cytosolic components of NAD(P)H oxidases, BAECs expressed p67phox and, to a lesser extent, p47phox, Noxo1, and Noxa1. Both NADH and NADPH induced superoxide production of the BAEC membranes. The phagocyte-type cytosolic components, p47phox and p67phox, significantly enhanced the NADH-induced superoxide production of the BAEC membranes, whereas the components failed to increase the NADPH-induced superoxide production. CONCLUSIONS: Nox1 is highly expressed in the endothelial cells of the cerebral arteries along with Nox2 and Nox4, and the endothelial NAD(P)H oxidase of the cerebral arteries may have a unique activation mechanism by the phagocyte-type cytosolic components.

Animals↗
PubMed2005

Postischemic gene transfer of interleukin-10 protects against both focal and global brain ischemia.

BACKGROUND: Gene therapy may be a promising approach for treatment of brain ischemia, although the efficiency of postischemic gene therapy is not established. Our goal in this study was to examine the effects of gene transfer of interleukin-10 (IL-10), an antiinflammatory cytokine, after induction of brain ischemia. METHODS AND RESULTS: Brain ischemia was produced by either photochemical occlusion of distal middle cerebral artery for focal ischemia or bilateral carotid occlusion for global ischemia in spontaneously hypertensive rats. Adenoviral vectors encoding human IL-10 (AdIL10) or beta-galactosidase (control) were injected into the lateral ventricle 90 or 60 minutes after focal or global ischemia. Five days after ischemia, IL-10, IL-1beta, or tissue necrosis factor-alpha in the cerebrospinal fluid, infarct volume, infiltrations of leukocytes/macrophages in the infarct area, or hippocampal neuronal damages were determined. The transduced IL-10 was released to the cerebrospinal fluid from the ventricular wall and increased to 7623+/-2965 pg/mL 5 days after AdIL10 transfection. Cerebral blood flow during ischemia was not different between treatments in either focal or global ischemia. Brain infarction of the AdIL10 group was significantly smaller and infiltrations of leukocytes and macrophages were fewer in the IL-10 treatment than control. Hippocampal neurons after global ischemia were more preserved, and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling-positive cells were diminished by the IL-10 gene transfer with attenuated IL-1beta and augmented tissue necrosis factor-alpha. CONCLUSIONS: Postischemic gene transfer of IL-10 into the lateral ventricle attenuated brain infarction and hippocampal damages, suggesting the promise for treatment of brain ischemia.

Animals↗
PubMed2005

Stroke in patients on maintenance hemodialysis: a 22-year single-center study.

BACKGROUND: Few studies have reported the detailed clinical features of stroke in patients with end-stage renal disease. We examined the frequency of the subtypes, mechanism, and outcome of stroke in patients receiving hemodialysis (HD). METHODS: We studied 151 consecutive patients who developed an acute stroke among the maintenance HD population in our kidney center during 22 years, divided into the initial 17-year (n = 61) and the more recent 5-year (n = 90) groups. For purposes of comparison, we also studied 1,017 stroke patients with normal renal function. RESULTS: Stroke patients receiving HD were younger (age, 64 +/- 10 versus 67 +/- 13 years; P < 0.02) and more frequently had hypertension (87% versus 43%; P < 0.0001) and diabetes (53% versus 23%; P < 0.0001) compared with stroke patients with normal renal function. In the initial HD group, brain hemorrhage was the major subtype of stroke (52%), whereas in the more recent group, brain infarction (BI) replaced hemorrhage as the leading subtype (68%; P < 0.005). In patients with BI, large-artery atherosclerosis was more prevalent in the more recent group than in the initial HD group (33% versus 12%; P < 0.05). A vertebrobasilar territory infarct was more prevalent for HD patients than for those with normal renal function (48% versus 33%; P < 0.05). BI (especially large-artery atherosclerosis and cardioembolism) occurred more frequently during or less than 30 minutes after the dialysis procedure (34%) than brain hemorrhage (19%; P < 0.05). Receiving HD was an independent indicator for poor functional outcome and mortality after stroke. CONCLUSION: In our maintenance HD population, stroke showed several unique characteristics compared with the control population, including a predominance of vertebrobasilar arterial territory infarcts. The dialysis procedure itself seems to be associated more frequently with ischemic rather than hemorrhagic strokes.

Aged↗
PubMed2004

Anti-monocyte chemoattractant protein-1 gene therapy protects against focal brain ischemia in hypertensive rats.

Monocyte chemoattractant protein-1 (MCP-1) is expressed in the ischemic cortex after focal brain ischemia and appears to exacerbate ischemic damage. The authors examined the effect of gene transfer of dominant negative MCP-1, called 7ND, 90 minutes after induction of focal brain ischemia in hypertensive rats. Adenoviral vectors encoding mutant MCP-1 (Ad7ND; n = 11), or Escherichia coli beta-galactosidase (AdlacZ; n = 17) as control were injected into the lateral ventricle of male spontaneously hypertensive rats. Both AdlacZ (n = 12) and Ad7ND (n = 6) administration provided transgene expression as early as 6 hours after injection and the expression further increased on day 1, followed by a sustained detection on day 5. Five days after ischemia, infarct volume (75 +/- 13 mm, n = 5, mean +/- SD) significantly reduced to 72% of control (104 +/- 22 mm3, n = 5, P < 0.05) by 7ND gene transfer. Numbers of leukocytes in the vessels (48.3 +/- 32.9/cm2) and macrophage/monocyte infiltration (475.2 +/- 125.5/mm2) of the infarct area in the Ad7ND group were significantly less than those measured in the AdlacZ group (143.8 +/- 72.1/cm2 and 671.8 +/- 125.5/mm2, P < 0.05, respectively). In summary, the postischemic gene transfer of dominant negative MCP-1 attenuated the infarct volume and infiltration of inflammatory cells, suggesting potential usefulness of the anti-MCP-1 gene therapy.

Adenoviridae↗
PubMed2003

Incidence, etiology, and outcome of stroke in patients on continuous ambulatory peritoneal dialysis.

BACKGROUND: Little information exists on clinical features of stroke in patients receiving continuous ambulatory peritoneal dialysis (CAPD). The goals of this study was to clarify features of stroke in CAPD patients, to determine factors to predict onset of stroke during chronic CAPD, and to determine whether CAPD had an advantage over hemodialysis (HD) for prevention of stroke. METHODS: We determined features of stroke in 12 patients (14 attacks including 7 parenchymal and 1 subarachnoid hemorrhage and 6 infarction) among 188 consecutive patients on CAPD, and compared them with those of 137 stroke patients among 1,681 consecutive patients on hemodialysis. RESULTS: Incidence of stroke for CAPD patients (15.7 per 1,000 person-years) was high compared with that of HD patients (approximately 12) or general residents in our suburban town. Patients with stroke on CAPD were younger than those on HD (52 +/- 12 vs. 62 +/- 11 years, p = 0.008). Mean arterial pressure (MAP) of patients with stroke increased after the introduction of CAPD (p = 0.01), whereas that of patients without stroke did not change. Increase in MAP during chronic CAPD was related independently to the occurrence of total stroke or brain hemorrhage. The majority of CAPD patients with stroke (67%) were dead or dependent in the chronic stage of stroke. CONCLUSION: CAPD patients seem to have a greater risk of stroke than the general population primarily because of poor control of hypertension, presumably in part due to overhydration. CAPD does not seem to have an advantage over HD for the prevention of stroke.

Adult↗
PubMed2003

Brain ischemia augments exo-focal transgene expression of adenovirus-mediated gene transfer to ependyma in hypertensive rats.

The ependyma is one of the feasible targets for gene transfer to the brain. Using two different replication-deficient recombinant adenoviral vectors, AdCMVbetaGal or AdRSVIL10, we examined effects of cortical brain ischemia on transgene expression in the ependyma after administration of the vector into the lateral ventricle of spontaneously hypertensive rats (SHR). Expression of the reporter gene lacZ at the lateral ventricle was detected by histochemistry for semiquantitative scoring or by biochemical assay for quantitative analysis. Ependymal cells in the ventricles expressed the transgene as early as 6 h after gene transfer in both sham treatment and ischemia treatment. In the sham treatment, the expression peaked at 12 h and slowly decreased toward day 4 and day 7. However, transgene expressions in the ischemic brain on day 4 and day 7 were significantly higher than sham treatment. In the biochemical assay, beta-galactosidase activity detected on day 4 at the periventricular area of the ischemic group (37 +/- 9 mU/mg protein) was significantly greater than that of the sham group (12 +/- 4, P < 0.01). In the enzyme-linked immunosorbent assay for gene transfer of interleukin-10 (IL-10), IL-10 in the cerebrospinal fluid (CSF) of the ischemic group (11,633 +/- 4322 pg/ml) was significantly greater than that in the sham group (2460 +/- 1486, P < 0.05) on day 5. These results suggest that transgene expression in the exo-focal remote area of ependyma is augmented by cortical ischemia, and the ependyma may be a promising target of gene transfer of brain ischemia.

Adenoviridae↗
PubMed2002

Bilateral deafness as a prodromal symptom of basilar artery occlusion.

Bilateral deafness is a rare but possible symptom for ischemia of the vertebrobasilar system, primarily derived from occlusion of anterior inferior cerebellar arteries or their branches. Patients 1 and 2 developed sudden bilateral deafness, soon followed by coma. The proximal segment of the basilar artery was occluded due to atherothrombosis in Patient 1 and arterial dissection in Patient 2. Thrombolytic therapy failed to recanalize the basilar arterial flow. Both patients died of extensive infarction in the vertebrobasilar arterial territory. Sudden bilateral deafness can be a warning sign of imminent brainstem ischemia by occlusion of the basilar artery regardless of age. Prompt and intensive management for stroke is needed for patients with sudden bilateral deafness.

Adult↗
PubMed2002

Hypertensive encephalopathy extending into the whole brainstem and deep structures.

In patients with hypertensive encephalopathy, brain edema is frequently distributed in the parieto-occipital white matter. We report a patient with high arterial blood pressure of over 300/160 mmHg on admission, who had extensive MRI-documented reversible lesions throughout the whole brain, including the brainstem, thalami, basal ganglia, and cerebellum. Extraordinarily severe acceleration of hypertension may be essential for the breakdown of autoregulation in the deep structures, especially in the brainstem including medulla.

Aged↗
PubMedDate not supplied

Brain ischemia as a potential target of gene therapy.

Brain infarction is one of the most important age-associated medical conditions, and the age-related neuronal vulnerability to brain ischemia is suggested to play an important role. Recent advancements in gene transfer techniques have provided promising approaches to the treatment of brain ischemia. In experimental studies, the ischemic penumbra area can be targeted by gene transfer even after ischemic insult, and post-ischemic gene therapy seems effective in attenuation of ischemic damage in both global and focal brain ischemia. Perivascular approaches of gene transfer to the cerebral blood vessels through the subarachnoid space may lead to prevention of brain ischemia caused by vasospasm after subarachnoid hemorrhage. Gene transfer to cerebral blood vessels and ischemic brain tissue may offer future therapeutic approaches to stroke.

Adenoviridae↗