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Biomedical subjects

N Otani

Publications and source records attributed to N Otani.

At least 19 recordsLinked to original sources

Alteration of gap junction proteins (connexins) following lateral fluid percussion injury in rats.

Gap junctions are intercellular channels that mediate the cytoplasmic exchange of small hydrophilic molecules and are formed by a family of integral membrane proteins called connexins (Cxs). Cx43 is expressed predominantly in astrocytes, while Cx36 is expressed in neurons. In this study, we show alteration of Cx43 and Cx36 in the hippocampus after traumatic brain injury in rats. Adult male Sprague-Dawley rats were subjected to lateral fluid percussion injury of moderate severity. Brain coronal sections were used for immunohistochemistry with Cx43 and Cx36 antibodies. Cx43 immunoreactivity was increased in reactive astrocytes in the damaged hippocampus 24 hours after injury, and persisted for 72 hours. On the other hand, Cx36 immunoreactivity increased in CA3 neurons 1 hour after injury, and decreased later. These results indicate that gap junctions might participate in the pathophysiological process after traumatic brain injury.

Adaptation, Physiological↗

Distal posterior inferior cerebellar artery aneurysms: clinical characteristics and surgical management.

BACKGROUND: Aneurysms located on the distal posterior inferior cerebellar artery (PICA) are rare, and their underlying clinical features and surgical management are poorly understood. We report our series of 16 patients with 18 distal PICA aneurysms. METHOD: All patients with distal PICA aneurysms were treated between March 1996 and August 2004. We excluded all PICA aneurysms that involved the vertebral artery. Patients were analysed in the light of their clinical profiles, radiological studies, intraoperative findings and outcomes. All patients underwent non-enhanced and contrast enhanced CT scans followed by 4-vessel cerebral angiography on admission. The hemorrhagic patterns on initial CT scans were assessed using the Fisher Grading Score. The outcomes were documented using the Glasgow Outcome Scale at time of discharge and at three or twelve months follow-up. FINDINGS: The series included 6 men and 10 women. Massive intraventricular haemorrhage was found in 13 patients with proven CT subarachnoid haemorrhage, one patient revealed SAH without intraventricular components, one presented with only intraventricular blood in the occipital horns and 3 aneurysms were found incidentally without presence of blood. Fourteen aneurysms were saccular and four were fusiform. Nine cases were associated with another cerebrovascular lesion. A lateral transcondylar or a median suboccipital approach was used to secure the aneurysms in 15 patients, either by direct clipping (14 lesions) or vessel sacrifice (3 lesions). One aneurysm was treated by an endovascular approach. At long-term follow up, an excellent or good outcome was achieved in 75% of cases. One patient died due to pre-existing cardiopulmonary complications. CONCLUSIONS: Most of our cases of ruptured distal PICA aneurysms presented with haematocephalus. These were frequently associated with another vascular abnormality and 22% were fusiform or multilobulated. These specific features require special management strategies entailing an appropriate surgical approach to the aneurysm, clipping method, haematoma removal, ventricular drainage and when suitable choice of endovascular interventions.

Adult↗

Focal brain edema and natriuretic peptides in patients with subarachnoid hemorrhage.

Central salt wasting syndrome may be caused by pathological increases in serum natriuretic peptides after subarachnoid hemorrhage (SAH). However, it is unclear as to why the serum concentration of atrial natriuretic peptide (ANP) or brain natriuretic peptide (BNP) increases in the subacute phase of SAH. The present study was designed to assess the correlation between focal brain edema and serum concentration of ANP or BNP in patients with SAH. Focal brain edema was found in 8 SAH-patients and peaked between days 4 and 7 of SAH. The mean serum ANP and BNP levels in patients with focal brain edema were significantly higher than those in patients without focal brain edema between days 4 and 14 of SAH. These results suggest that focal brain edema might correlate with increased levels of ANP and BNP in the subacute phase of SAH.

Atrial Natriuretic Factor↗

Vascular endothelial growth factor expression in pituitary adenomas.

Vascular endothelial growth factor (VEGF) is known to be a mediator of angiogenesis and vascular permeability. A cystic component and hemorrhage are often found in pituitary adenomas. In the present study we assess the VEGF expression based on immunohistochemical examinations in 48 pituitary adenomas. All the adenomas showed some VEGF immunoreactivity mainly in the cytoplasm of tumor cells. Of the 48 adenoma-cases, 16 cases had a strong VEGF immunoreactivity, 26 cases had a moderate one, and 6 cases had a weak one. On the MR images, a cystic component was found in 16 cases (33.3%), and a hemorrhage was found in 18 cases (37.5%). The VEGF immunoreactivity had a significant relationship with the cystic component but neither the hemorrhage, size, recurrence, or HE classification. These findings suggest that VEGF might play a potential role in the pathogenesis of cystic formation in pituitary adenomas.

Adenoma↗

Characteristic phosphorylation of the extracellular signal-regulated kinase pathway after kainate-induced seizures in the rat hippocampus.

Extracellular signal-regulated kinase (ERK) pathways play a crucial role in cell growth and long-lasting neuronal plasticity. Several studies have shown that phosphorylated-ERK (p-ERK) significantly increases after kainic acid (KA) administration. However, little or no information is available about the spatial distribution of p-ERK after KA-induced seizures. We herein show that KA-induced seizures significantly increase p-ERK in both neurons and astrocytes in rat brain using Western blots and immunohistochemistry. A strong immunoreactivity for p-ERK was induced in the dentate hilar neurons and CA3 neurons 30 mins and 6 hrs after KA injection. In addition, immunoreactivity for p-ERK was seen in astrocytes 6 hrs after KA injection. 72 hrs after KA injection, all pyramidal neurons had died. These findings suggest that the ERK pathway participates in the KA-induced neurotoxicity in the rat hippocampus.

Animals↗

Extracellular superoxide dismutase following cerebral ischemia in mice.

We describe the changes in extracellular superoxide dismutase (EC-SOD) following cerebral ischemia in mice. Mice were subjected to transient forebrain ischemia and reperfusion. The measurements of EC-SOD using ELISA showed increased brain EC-SOD after 24 h of reperfusion. The immunohistochemical examination showed that EC-SOD immunoreactivity in cortical and striatal capillary wall was conspicuous after 3 h. EC-SOD immunoreactivity was also noted in cortical neurons after 24 h. Northern blot analysis showed an increased EC-SOD mRNA expression in the brain after 24 h. In situ hybridization study demonstrated no mRNA expression of EC-SOD following ischemia and reperfusion in the capillary wall. These findings suggest that serum EC-SOD might accumulate on brain endothelial cells, while cortical neurons produce EC-SOD themselves after cerebral ischemia with reperfusion.

Animals↗

A role of glial fibrillary acidic protein in hippocampal degeneration after cerebral trauma or kainate-induced seizure.

Astrocytes perform a variety of functions in the adult central nervous system (CNS). Recent evidence suggests the robust upregulation of glial fibrillary acidic protein (GFAP) after CNS insult. However, little is known about the role of GFAP in the hippocampal degeneration after brain injury. We herein compared the GFAP knockout (KO) and wild type (WT) mice on the histological and behavioral outcome in response to cerebral trauma or kainic acid (KA)-induced seizure. Although all KO mice showed hippocampal CA3 neuronal degeneration. WT mice did not show any neuronal degeneration in CA3 subfield at 72 hrs after trauma. Thereafter, KO mice showed a higher susceptibility to KA-induced seizures and an increased number of pyknotic CA3 neurons 72 hrs after KA administration. These results indicate that GFAP plays a crucial role in the hippocampal neurodegeneration after CNS insult.

Animals↗

Mitogen-activated protein kinases phosphorylation in posttraumatic selective vulnerability in rats.

Mitogenic stimulation of the Mitogen-activated protein kinase (MAPK) pathway modulates the activity of many transcriptional factors leading to biological responses. Of these, three MAPK cascades are well characterized as extracellular signal-regulated protein kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), and p38 pathways. The aim of this study was to investigate the topographic distribution and the role of activated MAPK pathways after fluid percussion injury (FPI) in rats. In the present results, FPI significantly induced ERK- and JNK-phosphorylation, but not p38-phosphorylation in the cortex and hippocampus at the injury site. The immunoreactivity for phospho-ERK was localized in the superficial neuronal layers, dentate hilar neurons, and the damaged CA3 neurons after 30 mins of FPI. Double immunostaining showed that phospho-ERK was prominent in astrocytes 6 hrs after TBI. The current results suggest that MAPK pathways are involved in signal transduction after FPI.

Animals↗

Female gender as a risk factor for hypokalemia and QT prolongation after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) often causes hypokalemia and QT prolongation. The sex disparities among 73 patients with SAH and 96 control subjects were examined. On the first day of SAH, the mean serum potassium level was significantly lower and the mean corrected QT interval was significantly longer in the female SAH group compared with either the female control or male SAH group. These findings suggest female susceptibility to hypokalemia and QT prolongation after SAH.

Acute Disease↗

Evaluation of spontaneous intracranial hypotension: assessment on ICP monitoring and radiological imaging.

We describe two recent cases of spontaneous intracranial hypotension. A 38-year-old woman developed a severe postural headache. Magnetic resonance imaging (MRI) showed marked dural enhancement. Histopathological findings of dural biopsy showed numerous dilated vessels in the dura, rather than hypertrophic change. Lumber CSF pressure was 5 cmH2O and RI cisternography suggested CSF leakage. A 58-year-old woman with postural headache and vertigo had bilateral subdural haematoma associated with diffuse dural enhancement on MRI. Lumber CSF monitoring confirmed persistent low pressure ranging from 0-5 cm H2O. MRI myelography revealed multiple CSF pouches along the whole spinal axis. CSF leakage was demonstrated on Radioisotope (RI) cisternography. Both cases described in this report were diagnosed as spontaneous intracranial hypotension caused by CSF leakage from spinal meningeal diverticula and were successfully treated by intravenous Factor XIII administration.

Adult↗

Suppression of cell proliferation by tissue plasminogen activator during the early phase after balloon injury minimizes intimal hyperplasia in hypercholesterolemic rabbits.

Thrombus formation is a key component of the pathogenesis of restenosis after arterial balloon injury. The purpose of this study was to determine whether intimal hyperplasia could be attenuated by infusion of recombinant tissue plasminogen activator (tPA). Forty-two Kurosawa and Kusanagi hypercholesterolemic rabbits were divided into tPA (n = 20) and control (n = 22) groups, the former receiving 7 days of continuous tPA infusion (0.6 mg/kg/day) via ear veins. The walls of the common iliac arteries were injured using 2.5-mm balloon catheters and then examined histologically 7, 14, 21, and 28 days later. Cell proliferation was assessed by immunohistochemical analysis of proliferating cell nuclear antigen (PCNA), and transforming growth factor (TGF)-beta immunohistochemistry was carried out to estimate cell proliferation and differentiation. It was observed that 28 days after balloon injury, intimal cross-sectional areas in the tPA group were significantly smaller than in controls (0.11 +/- 0.03 mm2 vs. 0.57 +/- 0.08 mm2, p < 0.01), as were ratios of the cross-sectional areas of the intima and media (0.21 +/- 0.07 vs. 1.06 +/- 0.18, p < 0.05). In addition, the numbers of PCNA-positive medial cells were significantly lower (0.06 +/- 0.01 vs. 0.36 +/- 0.08, p < 0.05) and TGF-beta-positive vessel wall areas were significantly smaller in tPA-treated animals 7 days after balloon injury (0.47 +/- 0.28% vs. 4.55 +/- 1.44%, p < 0.05). Thus infusion of tPA after arterial balloon injury appears to decrease medial cell proliferation and suppress intimal hyperplasia.

Animals↗

tPA via infusion catheters followed by continuous IV infusion for 3 days prevents intimal hyperplasia after balloon injury.

A rabbit model was used to examine the effects of tissue plasminogen activator (tPA) on development of intimal hyperplasia following balloon injury. Thirty-two hereditary hypercholesterolemic (KHC) rabbits underwent percutaneous transluminal coronary artery balloon catheterization and injury to the common iliac artery, after which they were divided into four groups: untreated (control); Dispatch catheterized-30 minutes local saline delivery [D(+)-tPA(-)]; D(+)-30 minutes local tPA delivery (0.6 mg/kg) [D(+)-tPA(30 min)]; and D(+)-30 minutes local tPA + 3 days intravenous infusion (0.6 mg/kg/24 h) [(D(+)-tPA(30 min + 3 d)]. Twenty-eight days later, the intimal cross-sectional areas of all three Dispatch catheterized groups were significantly smaller than those of control groups, as were the intimal/medial area ratios. Moreover, the intima/media ratios of the D(+)-tPA(30 min + 3 d) group were significantly smaller than those of the D(+)-tPA(-) group. Thus, local delivery of tPA via Dispatch catheters followed by continuous intravenous infusion of tPA for 3 days prevented intimal hyperplasia after angioplasty.

Angioplasty, Balloon, Coronary↗

Anomalous internal carotid artery associated with ipsilateral cerebral arteriovenous malformation--case report.

A 15-year-old girl presented with an extremely rare anomalous origin of the internal carotid artery (ICA) from the common carotid artery, associated with an arteriovenous malformation in the brain and aberrant course of the ICA in the temporal bone. These anomalies, which were found on the same side, may be due to a maldevelopment of the vascular network including the aortic arches.

Adolescent↗

Peduncular hallucinosis due to a pineal meningioma. Case report.

The authors report the case of a 53-year-old woman who experienced visual hallucinations diagnosed as peduncular hallucinosis (PH). The cause of the PH was compression of the quadrigeminal plate and/or the splenium due to a meningioma originating from the falcotentorial junction (pineal meningioma). The nature of the visual hallucinations was depicted in drawings created by the patient herself. This is the first report of PH caused by a tumor located in the pineal region.

Female↗

Prevention of coronary arterial renarrowing by continuous 3-day infusion of tissue plasminogen activator after successful percutaneous transluminal coronary angioplasty: a randomized, double-blind, placebo-controlled study.

Vascular injury resulting from percutaneous transluminal coronary angioplasty (PTCA) and subsequent thrombus formation are important factors in the pathogenesis of coronary arterial restenosis. The present study was undertaken to determine whether infusions of tissue plasminogen activator (tPA), beginning immediately after PTCA, would decrease the renarrowing of the coronary arterial lumen. Patients were randomized and divided into two groups: one group (15 patients, 16 lesions) received continuous, 3-day, intravenous infusions of tPA (0.25 mg/kg/day in 0.9% saline), beginning immediately after successful PTCA, while the other group (17 patients, 17 lesions) received saline alone. Coronary angiography was performed before, immediately after, 24 hours after, and 3 months after PTCA. Coronary stenosis (%), reference diameters, and minimum luminal diameters were measured by quantitative coronary angiography. The incidence of restenosis tended to be lower in the tPA group than in the placebo group (tPA group, 13%; placebo group, 41%; NS), although diameter stenoses before and immediately after PTCA were not significantly different in the two groups. Three months later, however, diameter stenoses were significantly smaller in the tPA group (35.6 +/- 13.3 vs 47.7 +/- 18.9%; P<0.05). Thus, intravenous tPA infusion beginning immediately after successful PTCA may inhibit renarrowing of the coronary arterial lumen.

Aged↗

The vascular endothelial growth factor/fms-like tyrosine kinase system in human ovary during the menstrual cycle and early pregnancy.

In human ovaries, angiogenesis is known to be associated with the development of follicles and the formation of the corpus luteum (CL). A complex vascular network is formed within the thecal cell layer during follicular growth, and rapid neovascularization occurs toward the granulosa cell layer after ovulation. Vascular endothelial growth factor (VEGF) is a multifunctional cytokine, stimulating endothelial cell growth and enhancing microvascular permeability. A specific receptor for VEGF, fms-like tyrosine kinase (Flt-1), is expressed in vascular endothelial cells that mediates the action of VEGF. We examined the localization and expression of VEGF and Flt-1, using an immunohistochemical technique and RT-PCR analysis, in human follicles and corpora lutea during the normal menstrual cycle and early pregnancy. We measured concentrations of VEGF in extracts of human CL using an enzyme-linked immunosorbent assay during the luteal phase and early pregnancy. Immunostaining for VEGF was observed in granulosa cells from small antral follicles to preovulatory follicles. The staining was detected in thecal cells from medium-sized to preovulatory follicles. The intensity of the staining was gradually increased as a follicle grew. Flt-1 was localized in granulosa and thecal cells of preovulatory follicles as well as in endothelial cells. In the human CL, the intense staining for VEGF was observed in granulosa and thecal lutein cells, especially in the midluteal phase. The immunostaining for Flt-1 was faint in endothelial cells in the CL, whereas it was distinct in granulosa and thecal lutein cells. The concentrations of VEGF in lutein extracts were high in the early and midluteal phases and tended to decrease toward the late luteal phase. During early pregnancy, a measurable amount of VEGF was detected. RT-PCR analysis demonstrated that messenger ribonucleic acids encoding VEGF121, VEGF165, and Flt-1 were expressed in the CL. These results suggest that VEGF might have an autocrine role in the ovulatory process and luteal function as well as a paracrine role in angiogenesis.

Adult↗