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Biomedical subjects

Hiroki Ohkuma

Publications and source records attributed to Hiroki Ohkuma.

At least 19 recordsLinked to original sources
PubMed2006

Inhibition of integrin alphavbeta3 ameliorates focal cerebral ischemic damage in the rat middle cerebral artery occlusion model.

BACKGROUND AND PURPOSE: Recent studies have shown that selective inhibition of specific subsets of intercellular adhesion molecules protects the brain during ischemia. We studied selective inhibition of integrin alphavbeta3 with cyclo [Arg-Gly-Asp-D-Phe-Val] (cRGDfV) in the rat middle cerebral artery occlusion model (MCAO). METHODS: Rats were treated before and after MCAO with cRGDfV. Physiological parameters, expression of integrin alphavbeta3, infarction volume, brain water content, Evans Blue exudation, IgG exudation, histology, immunohistochemistry, and western blotting were studied in 4 groups of animals: sham operation (n=13), untreated (n=18), nonfunctioning peptide treatment (n=19), and cRGDfV treatment (n=27). RESULTS: Treatment with cRGDfV reduced infarction, reduced brain edema, reduced exudation of Evans blue and IgG, and prevented fibrinogen deposition. Western blotting showed reduction of phosphorylated Flk-1 (a vascular endothelial growth factor [VEGF] receptor), reduction of phosphorylated FAK (an intracellular kinase phosphorylated in the presence of VEGF), reduction of VEGF, and reduction of fibrinogen in the cRGDfV treatment group. CONCLUSIONS: The selective integrin alphavbeta3 inhibitor cRGDfV improves outcomes in the MCAO model by preserving the blood-brain barrier, which mechanistically may occur in a VEGF- and VEGF-receptor-dependent manner.

Animals↗
PubMed2006

Comparison of silicon-coated nylon suture to plain nylon suture in the rat middle cerebral artery occlusion model.

UNLABELLED: A variety of intraluminal sutures have been used in the middle cerebral artery occlusion model (MCAO) of focal ischemia. In the present study we tested commercially available silicon-coated nylon suture in the MCAO model and compared the results to traditional monofilament nylon suture occlusion. Twelve Sprague-Dawley male rats were randomly divided two groups, MCAO with 4-0 nylon suture (Group N, n=6) and MCAO with silicone-coated 4-0 nylon suture (Group S, n=6). Rats were sacrificed 24 h after reperfusion. Assessment included mortality rates, neurological evaluation, and infarct volume. One rat died in each group from subarachanoid hemorrhage. Neurological evaluation demonstrated that Group S tended to have worse neurological outcomes than Group N, although this difference was not statistically significant. On TTC stain Group S had significantly larger infarct volumes than Group N. We conclude that the commercially available silicone-coated occlusion suture provides better occlusion of the middle cerebral artery than the traditional uncoated nylon suture. CLASSIFICATION: Disease-related neuroscience (Section 6).

Animals↗
PubMed2006

Inhibition of integrin alphavbeta3 reduces blood-brain barrier breakdown in focal ischemia in rats.

Ischemic stroke is a major cause of morbidity and mortality in industrialized nations. We tested the effect of postischemic treatment of cyclo-RGDfV (cRGDfV), a selective inhibitor of integrin alphavbeta3, in the middle cerebral artery occlusion (MCAO) model of ischemic stroke in rats. Rats were randomly divided into three groups: sham operation (n = 13), MCAO with no treatment (n = 18), and MCAO with cRGDfV treatment (n = 28). Focal ischemia was induced with the suture occlusion method for 2 hr, and treatment was given 1 hr after reperfusion (3 hr after ischemia). All animals were sacrificed 24 hr after reperfusion. Assessment included neurological scores, infarction volumes, brain water content, Evans blue exudation, IgG exudation, histology, immunohistochemistry, and Western blotting. Treatment with cRGDfV ameliorated neurological deficits, reduced brain edema, and reduced exudation of Evans blue dye and IgG, but failed to reduce infarction volumes. Western blotting showed a reduction in phosphorylation of one subset of vascular endothelial growth factor (VEGF) receptors in the cRGDfV treatment group. Western blotting also demonstrated a significant reduction of fibrinogen in the cRGDfV treatment group. We conclude that poststroke treatment with cRGDfV reduces blood-brain barrier breakdown in focal ischemia, possibly through inhibition of VEGF-mediated vascular breakdown.

Analysis of Variance↗
PubMed2006

Effect of clot removal and the different incidence of vasospasm between clipping and GDC.

The removal of subarachnoid clot has been thought to be effective for prevention of cerebral vasospasm. However, it is suggested that the incidence of cerebral vasospasm is not high in the cases where ruptured cerebral aneurysms are obliterated using Guglielmi detachable coils (GDC) without clot removal. The effect of subarachnoid clot removal on the occurrence of cerebral vasospasm and the different incidence of cerebral vasospasm between clipping cases and in GDC cases are reviewed.Surgical clot removal in experimental model indicated marked preventive effect on cerebral vasospasm. However, the clinical trials of clot removal during early aneurysm surgery had failed to show satisfactory preventive effect for vasospasm, and the cumulative incidence of symptomatic vasospasm in these trials was 29%. As fibrinolytic drug, intrathecal administration of tissue plasminogen activator showed sufficient elimination of subarachnoid clot and prevention of cerebral vasospasm in the experimental studies and in the clinical case trials and nonrandomized case-control trials. However, the multi-center, randomized case-control trial showed no statistically significant effect on symptomatic cerebral vasospasm. On the other hand, the cumulative incidence of cerebral vasospasm in GDC cases was 20%. The comparative studies of the incidence of vasospasm between GDC cases and in clipping cases also showed less incidence of symptomatic vasospasm and a more favorable outcome in GDC cases. From the results of studies reviewed, the incidence of cerebral vasospasm seems less in GDC cases than in clipping cases. It should be clarified why clipping could not be dominant in the prevention of cerebral vasospasm compared to GDC.

Animals↗
PubMed2006

[Leiomyosarcoma of the uterus metastatic to the brain].

A case of 52-year-old female presented with dysarthria and paresis of right upper extremity 3 years after an operation and chemotherapy for uterine leiomyosarcoma. Magnetic resonance imaging showed an enhanced mass in the left corona radiata. Brain biopsy was carried out and pathological examination of the specimen showed features of a leiomyosarcoma. Uterine leiomyosarcoma is an uncommon tumor and its metastasis to the brain is rare. Only 13 other cases have been published. The patient underwent gamma-knife therapy and obtains good quality of life.

Brain Neoplasms↗
PubMed2004

Usefulness of acellular dermal graft as a dural substitute in experimental model.

BACKGROUND: Friction injury of cortical surface or cerebrospinal fluid leakage are the major complications of polytetrafluoroethylene (ePTFE) duraplasty because of their strong surface tension and lesser adaptability. Autologous duraplasties are also accompanied by potential donor-site complications and are inappropriate for large defects. Acellular Dermal Graft (ADG), prepared from cadaver human skin, does not have the above-mentioned drawbacks because of its human nature. Moreover, the dermal basement membrane and supporting tissues remain intact, so the rate of cellular migration and transformation to the surrounding host tissue is supposed to be excellent. We studied ADG in canine model to observe the rate of transformation into the surrounding dura mater via collagen synthesis from the invaded fibroblasts to evaluate its usefulness as a duraplasty. METHODS: Dural grafting surgery was performed on 6 adult mongrel dogs weighing from 8 to 12 kgs under general anesthesia. Three dogs were sacrificed after 1 month (acute) of surgery and the other three (chronic) were sacrificed after 3 months with overdose of pentobarbital sodium. Transcardiac perfusion-fixation with 4% paraformaldehyde was done. Hematoxylin-eosin and trichrome masson stains were performed to see the graft cellularity. Thickness of grafts was also assessed along the length of the histologic sections. RESULTS: Duralization, which was microscopically characterized by infiltration with regular array of collagen fibers, was observed at a few places in every high-power field in acute group. But in chronic animals, where dermal side of ADG was facing towards cranium, duralization was excellent. CONCLUSIONS: Our result suggests that ADG can be considered as a useful dural substitute.

Animals↗
PubMed2003

Measurement of ankle brachial index for assessment of atherosclerosis in patients with stroke.

BACKGROUND: Though atherosclerosis is generally regarded as a risk factor for stroke, its quantitative assessment in patients with stroke has not yet been reported. Recently, the ankle brachial index (ABI) has been receiving increasing attention as a noninvasive measurement of atherosclerosis. In this study, we investigated ABI to determine the degree of atherosclerosis in patients with stroke. METHODS: ABI was measured in 114 patients who had suffered a stroke, and the significance of differences between the ABI of the stroke subgroups and that of the normal group was investigated. The correlation of ABI with the degree of cerebral artery stenosis was also investigated. RESULTS: There was no significant difference in ABI between the hemorrhagic groups and the normal group, but in the infarction group (p = 0.0002) ABI was significantly less than the normal group. ABI was significantly correlated with the degree of stenosis in the intracranial internal carotid artery and middle cerebral artery (p < 0.0001, respectively). CONCLUSIONS: A strong relationship between ischemic stroke and atherosclerosis was demonstrated quantitatively by ABI measurement. A decrease in ABI may be a risk factor for ischemic stroke.

Aged↗
PubMed2003

A case of definitely congenital glioblastoma manifested by intratumoral hemorrhage.

BACKGROUND: A female infant was born with a left-sided glioblastoma that manifested clinically with weakened crying and feeding on day 1 of life, fever and bulging anterior fontanel on day 4, and right hemiparesis by day 10. METHODS: Preoperative magnetic resonance imaging showed hemosiderin intensity indicating that hemorrhage had occurred during the prenatal period. Radical surgical removal of the tumor was performed on the 22nd postnatal day. RESULTS: Postoperatively, the right hemiparesis did not worsen and the patient did not have any new neurological deficits. The right hemiparesis gradually improved after her initial surgery, and she was able to stand by herself at 18 months of age. Adjuvant chemotherapy and radiation were administered. This patient survived for 27 months following birth, which is a relatively long time for glioblastoma cases. Radical removal at the first operation with reliance on the plasticity of infant cerebral function was the key point in the long survival.

Adult↗
PubMed2003

Role of a decreased expression of the local renin-angiotensin system in the etiology of cerebral aneurysms.

BACKGROUND: Local renin-angiotensin systems (RAS) have been implicated as playing an important role in vascular remodeling. The relationship of this system to the etiology of cerebral aneurysm was investigated. METHODS AND RESULTS: The aneurysmal wall from patients with a ruptured or unruptured cerebral aneurysm and the cortical cerebral artery in control patients with head trauma or a glioma were taken during surgery for study. Local RAS were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and/or immunohistochemistry. RT-PCR analysis revealed a significantly decreased expression of angiotensin-converting enzyme (ACE), angiotensin type 1 (AT1) receptor, basic fibroblast growth factor, platelet-derived growth factor-AA, and tissue inhibitor of matrix metalloproteinases-1 mRNA in the aneurysmal wall as compared with the control cortical arterial wall. Immunohistochemistry also revealed a decreased expression of ACE, AT1 receptor, and angiotensin II in the aneurysmal wall. CONCLUSIONS: Expression of local RAS was decreased in the aneurysmal wall, which may induce aneurysm formation caused by a lack of vascular remodeling that prevents the arterial wall from thickening under increased hemodynamic stress. This is the first report that suggests that a decreased expression of local RAS plays a part in the pathogenesis of any disease.

Angiotensin II↗
PubMed2003

Phenotypic modulation of smooth muscle cells and vascular remodeling in intraparenchymal small cerebral arteries after canine experimental subarachnoid hemorrhage.

Cerebral microcirculatory changes are an important factor regulating cerebral blood flow. The aim of this study was to investigate the possibility of phenotypic modulation of smooth muscle cell (SMC) and vascular remodeling of intraparenchymal small cerebral arteries after subarachnoid hemorrhage (SAH). Seven to 14 days after canine experimental SAH, in intraparenchymal perforating arteries, the amount of beta-actin mRNA evaluated by Northern blot analysis increased, the structural change of the 3' untranslated region of beta-actin mRNA detected by polymerase chain reaction analysis was enhanced, and immunohistochemistry showed marked induction of the embryonal isoform of myosine heavy chain accompanied by decreased expression of smooth muscle myosin heavy chain (SM2). Histological morphometric analysis showed an increase in the area of the arterial wall without changes in the number of nuclei of SMC. This is the first report suggesting that vascular remodeling accompanied by phenotypic modulation occurs in intraparenchymal small arteries. These changes may affect cerebral blood flow after SAH by inducing increased cerebrovascular resistance.

Actins↗
PubMed2003

Effects of thrombin inhibitor on thrombin-related signal transduction and cerebral vasospasm in the rabbit subarachnoid hemorrhage model.

BACKGROUND AND PURPOSE: Thrombin is activated in the cerebrospinal fluid (CSF) after a subarachnoid hemorrhage (SAH). However, the relationship between thrombin and cerebral vasospasm has not yet been fully established. The aim of this study was to investigate the possibility of thrombin as a causative factor for cerebral vasospasm and to delineate the signal transduction mechanism that results in thrombin-inducing sustained vasoconstriction in cerebral vasospasm. METHODS: In the SAH group, SAH was simulated by the 2-hemorrhage rabbit model. In the treatment group, antithrombin III (AT-III) was injected into the cisterna magna just before production of the SAH. CSF samples were obtained serially to measure d-dimer with latex photometric immunoassay. On day 4, the basilar artery was excised after perfusion-fixation. The degree of cerebral vasospasm was evaluated by measuring the cross-sectional area of each basilar arterial lumen, and the expression of mitogen-activated protein kinase (MAPK) in the vascular wall was examined with an immunohistochemical technique. RESULTS: In the treatment group, the value of d-dimer on day 4 was 0.83+/-0.07 microg/mL, which was statistically significantly lower than that in the nontreated SAH group (2.49+/-0.09 microg/mL, P<0.01). The cross-sectional area of the arterial lumen in the treatment group was 3.67x10(5)+/-1.58x10(4) square pixels, which was statistically significantly larger than that in the nontreated SAH group (2.60x10(5)+/-2.29x10(4) square pixels; P<0.01). MAPK was detected diffusely in the vascular smooth muscle cell layer in the nontreated SAH group, but it was absent in the treatment group. CONCLUSIONS: Inhibition of thrombin activity leads to amelioration of cerebral vasospasm and suppression of MAPK diphosphorylation. This suggests that thrombin and its related signal transduction, including the MAPK cascade, appear to play an important role in the pathogenesis of cerebral vasospasm after SAH.

Animals↗
PubMed2003

Risk factors for aneurysmal subarachnoid hemorrhage in Aomori, Japan.

BACKGROUND AND PURPOSE: Japan is known to have an incidence of aneurysmal subarachnoid hemorrhage (SAH) as high as that in Finland, where SAH is especially common. However, the risk factors for SAH in Japan are unknown. The purpose of this study was to identify the risk factors and then examine their possible roles in cases of SAH in Japan. METHODS: Case-control data were collected in the Aomori prefecture between June 2000 and May 2001 and in the Shimokita area between 1989 and 1998. A history of hypertension, cigarette smoking, alcohol consumption, hypercholesterolemia, and diabetes mellitus were examined as possible risk factors for SAH by using stepwise logistic regression analysis. RESULTS: Stepwise logistic regression analysis showed that a history of hypertension and current smoking increased the risk of SAH and that a history of hypercholesterolemia decreased the risk of SAH. Alcohol consumption and a history of diabetes mellitus were excluded from the model, because their log-likelihood ratios were not significant. The adjusted odds ratios, obtained by forcing matching factors, were 2.29 for a history of hypertension (95% CI, 1.66 to 3.16), 3.12 for current smoking (95% CI, 2.05 to 4.77), and 0.41 for a history of hypercholesterolemia (95% CI, 0.24 to 0.71). The prevalence of hypertension in control subjects was 27% in men and 31% in women, whereas the prevalence of cigarette smoking in control subjects was 46% in men and 9% in women. CONCLUSIONS: Hypertension and cigarette smoking seem to be independent risk factors for SAH in Japan. The high prevalence of hypertension in both sexes and the high prevalence of cigarette smoking in men in the general population might contribute to the high incidence of SAH in Japan.

Case-Control Studies↗
PubMed2003

Pituitary abscess showing high uptake of thallium-201 on single photon emission computed tomography--case report.

A 32-year-old female presented with a rare case of pituitary abscess manifesting as homonymous hemianopsia. Serum prolactin level was slightly high (40.8 ng/ml). Magnetic resonance (MR) imaging showed the content of the lesion as homogeneously isointense on the T1-weighted images and hyperintense on the T2-weighted images. The capsule of the lesion, which appeared thin and smooth, was enhanced by gadolinium. Dural enhancement around the sella turcica was also recognized. Thallium-201 single photon emission computed tomography (201Tl SPECT) showed homogeneous high accumulation in the pituitary region on both the early and delayed images. The lesion was treated via a transnasaltranssphenoidal approach. The cystic lesion contained pus and the capsule consisted of normal pituitary gland with inflammatory changes. The patient was treated with antibiotics for 3 weeks and the pituitary abscess was cured completely. Pituitary abscess can be differentiated from pituitary adenoma as lesion with a homogeneous high uptake on 201Tl SPECT on both the early and delayed images, and no enhancement of the central portion on MR images.

Adult↗
PubMed2003

In vitro effects of new generation fungal derived nitric oxide donors on rabbit basilar artery.

The fungal derived nitric oxide donors, (E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409) and N-[(E)-4-ethyl-3-[(Z)-hydroxyimino]-5-nitro-3-hexen-1-yl]-3-pyridinecarboxamide (FR144420), were evaluated for the treatment and prevention of cerebral vasospasm induced by subarachnoid hemorrhage (SAH) by an in vitro study using rabbit basilar artery. The tension-relaxation of a 3 mm-long artery segment was carried out in a micro-tissue organ bath with a real-time recorder to record the tension-relaxation curve. Steady contraction of the specimens was induced by KCI (n = 12) and oxyhemoglobin (oxyHb) (n = 12). Sodium nitroprusside was used for comparison. Each of the agents was added in ascending concentration. Relaxation caused by FK409 and FR144420 was significantly greater (p < 0.05) than that by sodium nitroprusside. Relaxation effects of FK409 and FR144420 on the KCl-induced steady contraction were better than those on the oxyHb-induced contraction. FK409 and FR144420 have potential uses for the treatment and prevention of SAH-induced cerebral vasospasm.

Animals↗
PubMed2003

Cortical blood flow during cerebral vasospasm after aneurysmal subarachnoid hemorrhage: three-dimensional N-isopropyl-p-[(123)I]iodoamphetamine single photon emission CT findings.

BACKGROUND AND PURPOSE: The relationship between regional cerebral blood flow (rCBF) during cerebral vasospasm after subarachnoid hemorrhage (SAH) and angiographic vasospasm and the value of rCBF in predicting vasospasm and the prognosis are not fully delineated. Our aim was to investigate the changes in extent of vasospasm-induced decreased cortical rCBF on three-dimensional (3D) displays of single photon emission CT (SPECT) findings. The clinical usefulness of these assessments was analyzed. METHODS: In 58 cases of SAH, SPECT and digital subtraction angiography were performed on the same day, 5-9 days after SAH or within 24 hours after the onset of delayed ischemic neurologic deficit (DIND). Cerebral blood flow data were assessed by measuring the area of decreased cortical rCBF on 3D SPECT images. RESULTS: The area of decreased cortical rCBF on the 3D images was significantly increased in cases with DIND (P <.001), in cases with a large infarction due to vasospasm (P =.006), and in cases with a poor prognosis after vasospasm (P =.045). These increases were also related to the type of angiographic vasospasm; the greatest decrease in cortical rCBF occurred in the combined type (combination of the peripheral and proximal types) of vasospasm, followed by cases with the peripheral type, proximal type, and no angiographic vasospasm. In cases with DIND, patchy decreased cortical rCBF areas were seen before the onset of DIND. CONCLUSION: Combined-type vasospasm leads to reductions in CBF greater than those due to isolated peripheral or proximal vasospasm. Two-dimensional and mean-hemispheric CBF analyses are less sensitive for this change than is 3D SPECT.

Adult↗
PubMed2003

Neuroradiologic and clinical features of arterial dissection of the anterior cerebral artery.

BACKGROUND AND PURPOSE: Case reports of nontraumatic arterial dissection of the anterior cerebral artery (ACA) have recently increased. The aim of this study was to investigate the neuroradiologic and clinical features of ACA dissection based on a series of collected cases. METHODS: The cases of 18 patients with a diagnosis of ACA dissection based on clinical signs and neuroradiologic findings from 46 stroke centers during a 5-year period were collected. The neuroradiologic and clinical records were analyzed. RESULTS: The mean patient age was 52.8 +/- 9.8 years. Five cases presented with subarachnoid hemorrhage, nine with cerebral ischemia, and four with both ischemic symptoms and subarachnoid hemorrhage. In cases presenting with ischemia, the main site of the lesion was the A2 portion and the main angiographic finding was stenosis with or without dilation. Follow-up angiography showed progression of the stenosis in the acute stage and resolution of the stenosis in the chronic stage. Hyperintensity around the flow void due to intramural hematoma on T1-weighted MR images was often seen during the second week. In all cases, the findings of MR angiography corresponded to the findings of cerebral angiography. Eight of nine cases showed a good prognosis. In three of the patients with bleeding, in whom the site of the lesion was at the A1 portion, a diffuse thick subarachnoid hemorrhage was present and surgical treatment was required but resulted in a poor prognosis. In the other patients with bleeding, in whom the site of the lesion was at the distal ACA, the prognosis was good and no rebleeding or need for surgical treatment occurred. CONCLUSION: ACA dissection presenting with ischemia has several identifiable neuroradiologic and clinical characteristics, which suggests that it may be classified as a unique clinical entity.

Adult↗