Biomedical subjects

Y Fukuuchi

Publications and source records attributed to Y Fukuuchi.

At least 127 records · Page 7Linked to original sources

PubMed1994

Dilatation of cerebral microvessels mediated by endothelin ETB receptor and nitric oxide in cats.

The functional role of the endothelin (ET)B receptor in the cerebral microvessels was examined in seven anesthetized cats. The effects of intracarotidly injected IRL1620, a selective ETB receptor agonist, on the cerebral blood volume (CBV) in the cortex were examined by a photoelectric method. CBV reflects the cumulative dimensions of the cerebral microvessels. High doses of IRL1620 (0.1-1 nmol/kg) elicited a transient fall in CBV, followed by a marked and dose-related increase of CBV (P < 0.01). The CBV increase was significantly inhibited (P < 0.01) by simultaneous administration of 0.35 mg/kg/min NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis. The marked, but transient, depressor effect of IRL1620 was also attenuated (P < 0.01) by L-NMMA. The ETB receptor subtype and production of nitric oxide, probably in the endothelium, mediate the vasodilatory action of ET in the cerebral microvessels.

Animals↗

PubMed1994

A novel in vivo assay system for consecutive measurement of brain nitric oxide production combined with the microdialysis technique.

A novel spectrophotometric nitrite (NO2-)/nitrate (NO3-) assay system for a small quantity (5 microliter) of dialysate sample obtained by in vivo brain microdialysis was developed based on the diazotization reaction. The system has the advantage of in vivo consecutive measurement, high precision, good reproducibility, technical simplicity, relatively short resolution time (2.5-20 min), and wide availability. The NO3- level in the rat striatum was found to be 3 times higher than the NO2- level. A nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester, reduced striatal NO2-/citrulline formation in a dose-related manner and increased arginine, indicating that the tissue NO2- level detected by this assay system adequately reflects the striatal NO synthase activity.

Amino Acid Oxidoreductases↗

PubMed1994

Modification of striatal arginine and citrulline metabolism by nitric oxide synthase inhibitors.

The effects of NG-substituted L-arginine (ARG) analogues on striatal ARG and citrulline (CIT) levels were investigated using in vivo microdialysis technique. A microdialysis probe was implanted into the striatum of anaesthesized Sprague-Dawley rats. Direct intrastriatal perfusion with 1 mM NG-nitro-L-arginine methyl ester (n = 8) increased striatal ARG release and decreased CIT release, suggesting suppressed NO synthase activity in the tissue. On the other hand, 1 mM NG-monomethyl-L-arginine (L-NMMA) (n = 6) evoked a persistent increase in both ARG and CIT. Considering that 4-320 microM L-ARG (n = 8) failed to increase CIT formation, CIT seems to be synthesized in the striatal tissue from L-NMMA by the enzyme that has been demonstrated in the kidney and aortic endothelium (NG,NG-dimethylarginine dimethyl-aminohydrolase).

Amino Acid Oxidoreductases↗

PubMed1994

Cerebral ischemia-induced amplification phenomenon of somatosensory evoked potentials in cats.

We elucidate the amplification phenomenon of median nerve somatosensory evoked potentials (SEPs) induced in cats by cerebral ischemia and also analyse the relationship between such amplification and cerebral blood flow (CBF). Transient focal cerebral ischemia was carried out by inducing only middle cerebral artery occlusion or jointly with bilateral common carotid artery occlusion. Various SEP alteration patterns were observed with CBF changes; with our overall results suggesting for the first time that the SEP amplification phenomenon occurs only under relatively mild cerebral ischemia.

Animals↗

PubMed1994

Differential behavior of glial and neuronal cells exposed to hypotonic solution.

The comparative modes of swelling of glial and neuronal cells were examined by video-enhanced differential interference contrast (VEC) microscopy. When exposed to hypotonic solution, C6 cells swelled slowly to 5 times their normal volume and burst, whereas N18 cells swelled more rapidly, forming blebs, and then burst partially. The time to burst was 410.6 +/- 45.7 s (mean +/- SD, n = 5) for C6, and 69.3 +/- 10.4 s (n = 5, p < 0.01) for N18, respectively. The present findings suggest a great difference in physical strength of the cell membrane between glial and neuronal cells: the former cell membrane appears to be elastic and tolerant to high tension, while the latter cell membrane is relatively weak.

Animals↗

PubMed1994

Distribution and origins of cerebrovascular NADPH-diaphorase-containing nerve fibers in the rat.

Neuronal NADPH-diaphorase has been proved to be nitric oxide synthase itself. In this study, we investigated distribution and origins of NADPH-diaphorase-containing nerve fibers in the cerebral vessels in the rat. Adult male Sprague-Dawley rats were divided into 4 groups. Nasociliary nerves were transected bilaterally in group 1. In group 2, intracranial branches of the sphenopalatine ganglion were transected bilaterally. In group 3, both of these structures were transected. The remaining animals were served as control (group 4). Two weeks after the above procedures, they were perfused with paraformaldehyde and glutaraldehyde. The pial arteries and superior cervical, trigeminal, internal carotid, otic and sphenopalatine ganglia were dissected. All specimens were processed for NADPH-diaphorase histochemistry. Numerous NADPH-diaphorase-containing nerve fibers with varicosities forming plexuses were observed in the circle of Willis and its branches. Relatively thick nerve bundles were noted in the anterior half of the circle of Willis. They are most abundant in the internal ethmoidal artery. Approximately 5% of such fibers in anterior half of the circle of Willis disappeared in group 1, 90% in group 2, and no fibers were seen to remain in group 3. NADPH-diaphorase reaction was positive in the neurons of sphenopalatine, otic trigeminal and internal carotid ganglia. Among these ganglia, the reaction was prominent in sphenopalatine, otic and internal carotid ganglia. In summary: (1) NADPH-diaphorase-containing nerve fibers distribute to the circle of Willis and its branches.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Cerebral vasodilatory effect of high-dose, intravascular endothelin-1: inhibition by NG-monomethyl-L-arginine.

The effects of intracarotid administration of endothelin-1 on the cerebral microvessels were examined in anesthetized cats. The local cerebral blood volume in the cortex, which reflects the cumulative dimensions of the cerebral microvessels, was measured by our photoelectric method. A low dose of endothelin-1 (0.1 nmol) elicited mild but significant declines in cerebral blood volume. Following a high dose of endothelin-1 (3 nmol), the cerebral blood volume was initially reduced, probably due to the marked fall in arterial blood pressure, but was subsequently increased significantly. The increase in cerebral blood volume was not secondary to the rise in blood pressure, since it was unaffected by inhibition of the blood pressure changes with BQ-123 (1 mg/kg), an endothelin antagonist. However, the cerebral blood volume increase was prevented by continuous administration of NG-monomethyl-L-arginine (0.35 mg/kg per min), an inhibitor of nitric oxide synthesis, plus BQ-123. BQ-123 itself had no significant effects on cerebral blood volume or blood pressure. We conclude that while a low dose of intravascular endothelin-1 steadily constricts the cerebral microvessels, a high dose dilates the cerebral microvessels through the induction of nitric oxide synthesis, probably in the endothelium.

Animals↗

PubMed1994

Presynaptic glutamate receptors facilitate release of norepinephrine and 5-hydroxytryptamine as well as dopamine in the normal and ischemic striatum.

We investigated the effects of selective glutamate (Glu) agonists on the release of monoamine neurotransmitters and their implication in the enhanced monoamine release in cerebral ischemia. In the striatum of anesthetized Sprague-Dawley rats, in vivo microdialysis was performed and the release of excitatory amino acids (Glu and aspartate (Asp)) and monoamines (dopamine (DA), norepinephrine (NE) and 5-hydroxytryptamine (5-HT)) was measured by high-performance liquid chromatography with an electrochemical detector. (1) Forebrain ischemia by 4-vessel occlusion generated significant correlations between the Glu and Asp levels and the DA, NE and 5-HT levels (r = 0.922-0.967, P < 0.01, n = 6). (2) L-Glu and its selective agonists (N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and kainate (KA)) evoked a simultaneous release of striatal DA, NE and 5-HT in a dose-dependent manner (P < 0.01, ANOVA, n = 8). The maximal monoamine release evoked by the Glu agonists showed different magnitudes in the order of DA >> NE > 5-HT (118-, 16- and 9-fold from the baseline levels by 62.5 mM L-Glu, respectively). Each Glu agonist exerted a different magnitude of transmitter release and the order of agonist efficacy was different among NE, 5-HT and DA release: AMPA = KA > L-Glu = NMDA for DA release, AMPA > L-Glu = NMDA = KA for NE release, and L-Glu = NMDA = KA = AMPA for 5-HT release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Presynaptic ionotropic glutamate receptors modulate in vivo release and metabolism of striatal dopamine, noradrenaline, and 5-hydroxytryptamine: involvement of both NMDA and AMPA/kainate subtypes.

In order to explore further the presynaptic modulation of monoamine release by glutamatergic nerve fibers, we investigated the effects of selective agonists for ionotropic glutamate (GLU) receptors on striatal release of dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT). In the striatum of anesthetized Sprague-Dawley rats, in vivo microdialysis was performed to measure the release of monoamines and metabolities, and also to administer GLU agonists locally in the tissue. L-GLU and its selective agonists (N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and kainate (KA)) evoked simultaneous release of striatal DA, NA and 5-HT in a dose-dependent manner. Pretreatment with MK-801 (5 mg/kg i.p.), a noncompetitive NMDA receptor antagonist, selectively suppressed NMDA-evoked monoamine release. The rank order of GLU agonist efficacy in releasing monoamines was different among DA, NA, and 5-HTergic terminals: AMPA = KA > NMDA for DA release, AMPA > NMDA = KA for NA release, and NMDA = AMPA = KA for 5-HT release. In conclusion, presynaptic ionotropic GLU receptors exist extensively on monoaminergic terminals including not only catecholaminergic (DA and NA) but also indoleaminergic (5-HT) terminals in the rat striatum. Their subtypes include both NMDA subtype and AMPA/KA subtype, and show a differential distribution among these three monoaminergic terminals and a differential contribution to facilitating monoamine release.

Animals↗

PubMed1994

Enhanced maximal binding capacity (Bmax) of second messenger ligand in the acute phase of cerebral ischemia--direct visualization by digital image analysis.

Autoradiographic visualization of the Bmax (maximal binding capacity) and Kd (dissociation constant) of [3H]phorbol 12,13-dibutyrate (PDBu) and [3H]forskolin (FK) was performed after 30-min unilateral carotid artery occlusion in the gerbil brain. These parameters and the local cerebral blood flow (CBF) were measured at the level of the caudate-putamen in the same brain using a digital image processing technique developed in our laboratory. The local CBF was measured at the end of the experiment. [3H]PDBu and [3H]FK were utilized as specific ligands to assess the activities of protein kinase C (PKC) and adenylate cyclase (AC), respectively. The local CBF on the occluded side was severely reduced and ranged from 0.2 to 9.0 ml/100 g/min, whereas the local CBF on the non-occluded side exhibited a moderate reduction except in the midline regions. The Bmax values of PDBu and FK were significantly increased not only on the occluded side but also on the non-occluded side in the ischemia group as compared to the corresponding values in the sham group. In contrast, the Kd value of each ligand remained unchanged in the ischemia group. These findings suggest that both the adenylate cyclase and protein kinase C systems may be significantly and diffusely activated in the initial stage of brain ischemia. Thus, severe hemispheric cerebral ischemia in the acute phase may induce severe perturbation of the second messenger systems in extensive bilateral regions.

Acute Disease↗

PubMed1994

Alteration of inositol 1,4,5-trisphosphate receptor after six-hour hemispheric ischemia in the gerbil brain.

In order to evaluate the influence of cerebral ischemia on the inositol 1,4,5-trisphosphate receptor, the alterations of inositol 1,4,5-trisphosphate receptor binding sites and local cerebral blood flow were examined 6 h after occlusion of the right common carotid artery in the gerbil brain. The autoradiographic method developed in our laboratory enabled us to measure both parameters within the same brain. Animals attaining ischemic scores of more than 5, as assessed 1 h after occlusion, were utilized. The local cerebral blood flow was measured 6 h after occlusion by the [14C]iodoantipyrine method. The inositol 1,4,5-trisphosphate binding sites were evaluated in vitro using [3H]inositol 1,4,5-trisphosphate as a specific ligand. The local cerebral blood flow fell below 15 ml/100 g per min in most of the cerebral regions on the occluded side. In contrast, a significant reduction in inositol 1,4,5-trisphosphate binding sites was noted only in the hippocampus CA1 on the occluded side. Inositol 1,4,5-trisphosphate binding tended to decrease when the values of local cerebral blood flow were below 20 ml/100 g per min in this region. On the other hand, the inositol 1,4,5-trisphosphate receptor immunoreactivity in the brain examined with a monoclonal antibody against inositol 1,4,5-trisphosphate receptor protein did not reveal any differences between the ischemia and sham groups on both sides, suggesting that the inositol 1,4,5-trisphosphate receptors may not undergo significant morphological degradation. These findings indicate that the suppression of inositol 1,4,5-trisphosphate binding in the hippocampus CA1 may be attributable to a regionally specific perturbation of the inositol 1,4,5-trisphosphate metabolism in this region.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Constriction/dilatation of the cerebral microvessels by intravascular endothelin-1 in cats.

The effects of intracarotidly injected endothelin (ET)-1 (0.01-3 nmol) on the local cerebral blood volume (CBV) in the parietotemporal cortex were examined by the photoelectric method in 17 anesthetized cats. CBV reflects the cumulative dimensions of the cerebral microvessels. Low doses of ET-1 (0.01 and 0.1 nmol) elicited mild but significant reductions in CBV without changes in the systemic arterial blood pressure (SABP). High doses of ET-1 (3 nmol) initially induced marked declines of CBV, which were attributable to the significant falls in SABP. CBV subsequently exhibited significant increases. The CBV increases were not secondary to the accompanying elevations of SABP, since they were unaffected by inhibition of the SABP changes after preinjection of BQ-123 (1 mg/kg), an ET antagonist specific to the ETA receptors. The CBV increases, however, were prevented by continuous administration of NG-mono-methyl-L-arginine (0.35 mg/kg/min), an inhibitor of nitric oxide synthesis, plus BQ-123. We conclude that while low doses of intravascular ET-1 constrict the cerebral microvessels, high doses of ET-1 dilate the cerebral microvessels through the induction of nitric oxide probably in the cerebrovascular endothelium.

Animals↗

PubMed1994

A MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) mtDNA mutation that induces subacute dementia which mimicks Creutzfeldt-Jakob disease.

A 50-year-old woman with subacute dementia and brain atrophy on CT showed periodic synchronous discharge (PSD) on electroencephalogram (EEG) and myoclonus. She was initially suspected of suffering from Creutzfeldt-Jakob disease (CJD), but dramatically recovered over 5 months. Based on further investigations, the final diagnosis was mitochondrial encephalomyopathy with an A-to-G substitution at nucleotide position 3243 in mitochondrial DNA (mtDNA), commonly seen in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). This case suggests that patients suspected of suffering from CJD should be evaluated for mitochondrial encephalomyopathy.

Creutzfeldt-Jakob Syndrome↗

PubMed1994

Midpontine tegmentum infarction with "one-and-a-half syndrome" demonstrated by magnetic resonance imaging.

Magnetic resonance imaging (MRI) revealed a small midpontine tegmentum infarction in a patient with Fisher's one-and-a-half syndrome. The lesion was extremely restricted to the unilateral paramedian area of the midpontine tegmentum involving both the paramedian pontine reticular formation and medial longitudinal fasciculus. The typical form of this syndrome, that is, a combination of lateral gaze palsy and unilateral internuclear ophthalmoplegia, can be caused by a midpontine lesion.

Aged↗

PubMed1994

Spastic paraplegia with amyotrophy of the legs: a rare case of motor and sensory neuropathy.

A 36-year-old man who suffers from gait disturbance is reported. He noticed deformity of his feet at the age of 15. When he was 32 years old, he complained of heaviness in his lower extremities. Since then his legs have been always stiff. He had no previous illness or familial neuromuscular diseases. Neurological examination revealed no impairment of mental function or cranial nerves. Marked weakness and wasting of the feet were noted. The legs showed an inverted champagne bottle shape and pes cavus deformity was evident. Deep tendon reflexes were normal in the arms but abnormally brisk in the legs. Bilateral Babinski sign and ankle clonus were elicited. The patient tended to walk on his toes and the legs scissored. The motor nerve velocities were less than normal. Sural nerve biopsy showed reduced myelinated fiber density and increased endoneurial connective tissue. Electron microscopy showed axonal swellings filled with neurofilaments. Distal wasting and weakness involving the legs more than the arms resembled that of Charcot-Marie-Tooth disease. According to the classification by Dyck, this disorder could be referred to as hereditary motor and sensory neuropathy type V. Spastic paraplegia with amyotrophy is rare, but should be identified as a distinct disorder. Recognition of this disorder would imply the clinical and genetic heterogeneity of Charcot-Marie-Tooth disease.

Adult↗

PubMed1994

Mechanisms of CBF augmentation during hypoxia in cats: probable participation of prostacyclin, nitric oxide and adenosine.

To elucidate the mechanisms of CBF augmentation during hypoxemic hypoxia, we applied continuous monitoring of CBF and metabolism to examine the participation of prostacyclin, nitric oxide (NO), and/or adenosine in these mechanisms. Cats (n = 32) were anesthetized and ventilated artificially. Cerebrovascular reactivity to hypoxia was assessed by changes in CBF, brain tissue oxygen and carbon dioxide tensions, and mean arterial blood pressure (delta CBF, delta BrPO2, delta BrPCO2, and delta MABP) during a 3-min inhalation of 10% O2 + 90% N2 before and after the intracarotid administration of (1) indomethacin (1 mg/kg, a cyclooxygenase inhibitor, n = 11), (2) L-NG-monomethyl-arginine (LNMMA, 1 mumol/kg/min, an inhibitor of nitric oxide synthesis, n = 11), and (3) caffeine (20 mg/kg, an adenosine antagonist, n = 10). BrPO2 decreased significantly in all groups during the produced hypoxemic hypoxia. CBF significantly increased in this state before the administration of indomethacin, LNMMA, or caffeine, whereas it contrastively did not significantly increase after the administration of indomethacin or caffeine. In addition, CBF significantly decreased under hypoxia during the administration of LNMMA. Taken together, these results suggest that prostacyclin (PGI2), nitric oxide (NO), and adenosine may jointly participate in CBF augmentation during hypoxia.

Adenosine↗

PubMed1994

Paramyotonia congenita without cold paralysis: a case report.

A 27-year-old-woman with paramyotonia congenita was reported. She began to suffer from myotonia since infancy. Myotonia was aggravated by cold, but with intense cooling myotonia did not change to flaccid paralysis. Four generations of her family showed the same symptoms that suggested autosomal dominant inheritance. Neurological examinations revealed no impairments of mental function, cranial nerves and sensory system. Muscular atrophy or hypertrophy was not observed. Percussion myotonia of the tongue and thenar muscles could be elicited at room temperature. Myotonia was aggravated by cold. An oral intake of potassium chloride (7 grammes) did not provoke any muscle weakness or flaccid paralysis. Routine laboratory data and findings of head CT scan, cerebrospinal fluid and electroencephalogram were normal. The nosological distinction between paramyotonia congenita and hyperkalemic periodic paralysis has been debated since 1956. Paralysis induced by cold is thought to be a feature of paramyotonia congenita, thus raising a possible relationships to hyperkalemic periodic paralysis. In our case cold paralysis never occurred spontaneously and could not be provoked by immersion in ice water or by potassium loading. This finding confirms the existence of paramyotonia congenita without cold paralysis and may provide a nosological distinction between paramyotonia congenita and hyperkalemic periodic paralysis.

Adult↗

PubMed1994

Effect of sympathetic stimulation on cerebral circulation.

The role of sympathetic regulation in cerebral circulation was studied in the cat by continuous measurement of cerebral tissue oxygen tension (BrPO2), carbon dioxide tension (BrPCO2), pH(BrpH) and blood pressure. The ipsilateral superior cervical ganglion was electrically stimulated for 3 min. A slight decrease in BrPO2 and a slight but significant increase in BrPCO2 were observed during sympathetic stimulation. These changes suggested that sympathetic stimulation slightly decreased cerebral blood flow. The present results do not rule out a significant role for sympathetic regulation of cerebral circulation. Sympathetic constriction of the extraparenchymal vessels might be compensated for by secondary dilation of the intraparenchymal vessels elicited by a chemical control (escape phenomenon).

Animals↗