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Biomedical subjects

M Asanuma

Publications and source records attributed to M Asanuma.

At least 91 records · Page 5Linked to original sources
PubMed1993

[A case of progressive supranuclear palsy showing marked improvements of frontal hypoperfusion, as well as parkinsonism with amitriptyline].

A patient with progressive supranuclear palsy (PSP) showing severe akinesia, postural instability and gait disturbance like frozen gait was treated with amitriptyline (30 mg/day). Four weeks after drug administration, we recognized tendencies for improvement on akinesia, postural instability, frozen gait and vertical gaze palsy. Thereafter, gait disturbance almost disappeared and slow motor response and depression also improved with the amitriptyline for 8 weeks. The changes of cerebral blood flow (CBF) with amitriptyline treatment were evaluated in this case by 123I-IMP single photon emission computed tomography. Before the treatment, clear reduction of CBF was shown in the frontal lobes, especially in the frontal cortices, while this frontal hypoperfusion markedly improved 6 weeks after the treatment. These results, showing marked improvements of frontal hypoperfusion, as well as parkinsonism with amitriptyline treatment, may imply possibilities that these symptoms of PSP result from the frontal hypoperfusion and the improvement of the hypoperfusion with amitriptyline is involved in the improvement of these symptoms.

Amitriptyline↗
PubMed1992

Post-ischemic administration of bifemelane hydrochloride prohibits ischemia-induced depletion of the muscarinic M1-receptor and its mRNA in the gerbil hippocampus.

Parallel determinations of muscarinic cholinergic M1 receptor (M1-R) binding and of M1-R mRNA levels were carried out in the gerbil hippocampus 14 days after 5 min of transient ischemia. Both were reduced in the ischemic tissue to about 50% of the levels found in sham-operated controls, indicating that the late loss of M1-R is probably dependent on decreased synthesis. Three administrations of bifemelane hydrochloride (15 mg/kg, i.p., just after ischemia and 6 and 12 h later) completely prevented neuronal death in the hippocampus and ischemia-induced losses of hippocampal M1-R and its mRNA. Since vascular dementia may depend upon the ischemia-induced losses in cholinergic communication in the hippocampus, these findings suggest that it may be possible to prevent its occurrence by post-ischemic treatment with bifemelane hydrochloride.

Animals↗
PubMed1992

Effects of dihydroergotoxine on central cholinergic neuronal systems and discrimination learning test in aged rats.

We evaluated changes in the cholinergic neuronal system and learning ability with aging. Choline acetyltransferase (ChAT) activity, a presynaptic index of the cholinergic system, was decreased in the cerebral cortex, hippocampus, striatum, and hypothalamus in the brain of aged rats compared with young adults. Muscarinic cholinergic binding sites (receptors, MCR), a postsynaptic index of the cholinergic system, were markedly decreased in all areas of the brain. However, intraperitoneal injection of 1 mg/kg of dihydroergotoxine (DHET) for 14 days normalized both ChAT and MCR in the cerebral cortex and hippocampus. In the striatum, ChAT was normalized, but MCR did not recover. Aged rats showed marked learning impairment in a 30-day operant type brightness discrimination learning test. Daily DHET administration restored the discrimination ability in the aged rats to nearly the young adult level. DHET had no effects on central cholinergic indices or learning test results in young adult rats. These findings suggest that learning is impaired in aged rats due to impairment in the central cholinergic neuronal system, and that DHET normalizes the decreased function in this system, restoring the learning ability.

Aging↗
PubMed1992

Late onset and long-lasting suppressive effects of ceruletide, an analogue of cholecystokinin, on c-fos mRNA expression in the rat striatum.

C-fos mRNA expression by stimulation with subcutaneous (s.c.) administration of saline or cycloheximide (CHX) was examined in the rat striatum with or without pretreatment with ceruletide, an analogue of cholecystokinin. The c-fos mRNA induction 1 h after CHX stimulation (25 mg/kg, s.c.) was significantly suppressed by ceruletide pretreatment (80 micrograms/kg, s.c.) 2 h before CHX stimulation in the striatum, and tended to be suppressed by ceruletide pretreatment 4 h before saline or CHX stimulation. Long-lasting and inhibitory effects of ceruletide on dyskinesia and on dopaminergic (DAergic) neuronal systems, and c-fos mRNA expression by activation of the DAergic system have been reported. The present findings together with previous reports suggest that ceruletide might have late onset and long-lasting suppressive effects on the expression of c-fos mRNA in the striatum and that these effects might be related to its effects on DAergic neuronal transmission.

Animals↗
PubMed1992

Effects of chronic bifemelane hydrochloride administration on receptors for N-methyl-D-aspartate in the aged-rat brain.

We assayed N-methyl-D-aspartate (NMDA) receptors [3H]3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid ([3H]CPP) bindings) and evaluated their distribution in the brain by quantitative autoradiography in young adult and aged rats. In the young adult rats, NMDA receptors were present at relatively high concentrations in the cerebral cortex and hippocampus. In the aged rats, NMDA receptors were decreased in the nealy all areas of the brain, especially in the cerebral cortex and hippocampus. Chronic administration of bifemelane hydrochloride, a drug for sequela of cerebrovascular diseased, at a dose of 15 mg/kg/day for 14 days, markedly attenuated these decrease in NMDA receptors. Since NMDA receptors are considered to be involved in memory and learning processes, our results suggest that bifemelane hydrochloride may be applicable to the treatment of disturbed memory and learning.

Aging↗
PubMed1992

Comparison of the effects of bifemelane hydrochloride, idebenone and indeloxazine hydrochloride on ischemia-induced changes in brain monoamines and their metabolites in gerbils.

Bifemelane hydrochloride (bifemelane), idebenone and indeloxazine hydrochloride (indeloxazine) are used clinically to reduce apathy and other emotional disturbances in patients with cerebrovascular disease. In gerbil brains, ischemia affects many monoaminergic neurotransmitters and their metabolites. In the present study, the effects of treatment with bifemelane, idebenone and indeloxazine on ischemia-induced changes in monoamines and their metabolites were studied in ischemic gerbil brains. Although these drugs had no effect on the monoaminergic neurotransmitters or their metabolites in sham-operated animals, in the ischemic brains both dopamine and serotonin turnovers were abnormal after idebenone or indeloxazine treatment. Bifemelane, in contrast, tended to correct the ischemia-induced changes in the dopaminergic and serotonergic systems in the cerebral cortex, hippocampus and thalamus + midbrain. From the present results and those in previous reports, we conclude that bifemelane is more appropriate than idebenone or indeloxazine as a treatment for the ischemia-induced changes in monoaminergic neurotransmitter systems.

Animals↗
PubMed1992

Opposite effects of rough and gentle handling with repeated saline administration on c-fos mRNA expression in the rat brain.

The rough handling with repeated saline administration (1.2 ml/kg s.c. for 7 days) enhanced cortical c-fos mRNA expression in the rat brain after a single saline stimulation (1.2 ml/kg s.c.) due to increasing baseline c-fos mRNA levels, whereas the gentle handling with repeated saline administration declined c-fos mRNA expression after a single injection due to decreasing the baseline of c-fos mRNA levels. These two types of handling with the repeated injection led to diametrically opposite results on c-fos mRNA expression after a single stimulation. Neither two types of handling with repeated saline injections affected the net increment of c-fos mRNA induction after a single stimulation, therefore, the effects of handling with repeated treatment on c-fos mRNA expression might be independent of the effects of a single saline stimulation. The present study suggests that c-fos mRNA induction after a single stimulation might be affected by the types or intensities of handling and that care must be taken to estimate c-fos mRNA induction.

Animals↗
PubMed1992

Muscarinic cholinergic receptor-mediated modulation on striatal c-fos mRNA expression induced by levodopa in rat brain.

To clarify the interactions between dopamine receptors and muscarinic cholinergic receptors by which neurotransmitters may affect genetic responses, we studied the effects of the muscarinic cholinergic agonist, carbachol, and the muscarinic cholinergic antagonist, trihexyphenidyl, on levodopa-induced c-fos messenger RNA (mRNA) expression in rat striatum. Animals were administered levodopa (levodopa with one-tenth dosage of carbidopa), carbachol or thrihexyphenidyl alone or administered in combination as levodopa (100 mg/kg) + carbachol, or levodopa+trihexyphenidyl given as a single bolus. Levodopa given alone increase the expression of c-fos mRNA. Although carbachol or trihexyphenidyl alone was ineffective in inducing c-fos mRNA, the combination of levodopa and carbachol (> or = to 0.1 mg/kg) significantly suppressed the induction of c-fos mRNA as compared with levodopa given alone. The combined administration of levodopa and trihexyphenidyl showed a trend toward an additive effect on the induction of c-fos mRNA vs levodopa alone. These findings suggest that the muscarinic cholinergic system may modulate the levodopa-induced c-fos mRNA expression which then regulates the expression of other mRNAs.

Actins↗
PubMed1992

Effects of chronic catecholamine depletions on muscarinic M1-receptor and its mRNA in rat brain.

In order to compare the effects of total catecholamine (CA) or noradrenaline (NA) depletions on cholinergic systems, and the mechanisms of receptor regulation in various brain regions, the regional changes in the levels of acetylcholine (ACh), M1-receptor (M1-R) binding, and M1-R messenger RNA (mRNA) were mainly examined in rats which had received either repeated reserpine treatment or a single injection of the selective noradrenergic neurotoxin N-2-chloroethyl-N-ethyl-2-bromo-benzylamine (DSP-4). The levels of dopamine (DA), its metabolites, NA, binding to both D1 and D2 sites, and the mRNA encoding the D2 receptor were also measured. Administration of reserpine (0.5 mg/kg/day, s.c.) for 2, 7 and 14 days depleted DA and NA in virtually all brain regions, while the short-term treatment increased DA metabolites in the striatum (at 2 days) and basal forebrain (at both 2 and 7 days). Administration of DSP-4 (50 mg/kg, i.p.) resulted in a specific loss of NA in the brain 10 days after the injection. These DSP-4 treated rats showed no change in the levels of ACh or M1-R except for an increase in ACh in the frontal cortex. In contrast, numerous changes in cholinergic indices were seen in the reserpine treated groups, and these changes varied from region to region of brain and with the length of drug treatment. In the striatum, ACh levels were increased in rats treated for 2 or 7 days but were normal after 14 days. M1-Rs were decreased at 14 days. These changes suggest that striatal DA, initially released by reserpine, inhibits the release of ACh from striatal cholinergic interneurons, while prolonged depletion of DA relieves this inhibition, leading to a subsequent down-regulation of M1-Rs. In the frontal cortex, ACh and M1-R levels were all decreased by reserpine treatment for 2 or 7 days, and the M1-Rs remained depressed at 14 days. In the basal forebrain, which contains the cholinergic cells that project to the cortex, DA metabolism was increased by 2 or 7 day reserpine treatment. This increased DAergic activity in the basal forebrain may facilitate cholinergic neurons, causing increased release of ACh in the frontal cortex. This, in turn, may lead to a down-regulation of the M1-Rs in that region. The levels of mRNAs encoding M1-Rs were increased in the striatum and frontal cortex by reserpine treatment, despite the decreases in the M1-Rs themselves.(ABSTRACT TRUNCATED AT 400 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Changes of neuropeptides and their receptors in experimental stroke gerbil brains.

Eight kinds of neuropeptides and four kinds of neuropeptide receptors were examined in the right and left hemispheres of mongolian gerbils after unilateral carotid ligation-induced stroke and in normal controls. Five hours after ligation of the right common carotid artery, beta-endorphin concentration in the right hemisphere (ischemic side) of the stroke group was significantly increased compared with that in the contralateral hemisphere (non-ischemic side), but there were no differences between sides in other neuropeptides either with or without stroke. Furthermore, although there were no differences in [3H]naloxone binding, [3H]thyrotropin-releasing hormone binding or 125I-vasoactive intestinal polypeptide binding in the brain in this model of stroke, [3H]enkephalin binding was significantly lower on the ischemic side than on the non-ischemic side in the stroke group. These results suggest that increased activity in the beta-endorphinergic system in the brain might be partly caused by ischemic brain failure.

Animals↗
PubMed1992

Development of a simple spasticity quantification method: effects of tizanidine on spasticity in patients with sequelae of cerebrovascular disease.

A simple method that can be performed at the bedside using a spring balance was developed in order to quantify spasticity. The effects of tizanidine on spasticity were evaluated in 30 patients with sequelae of cerebrovascular disease using this method. Treatment with tizanidine was effective in 60% of the patients; there were high correlations between spasticity before and after tizanidine administration and the severity of symptoms and also between the degree of improvement in spasticity and in that of the symptoms. Atonic seizures, due to overdose of tizanidine, were observed in only one patient. The simple spasticity quantification method developed was useful for monitoring tizanidine administration in order to prevent drug overdose. The method appears to be very useful for evaluating the degree of spasticity at the bedside and in measuring the effects of antispastic drugs.

Aged↗
PubMed1992

Age-related changes in cerebrospinal fluid gamma-aminobutyric acid concentration.

The purpose of this study was to clarify the effect of aging on brain gamma-aminobutyric acid metabolism. We measured the cerebrospinal fluid gamma-aminobutyric acid concentration in subjects of various ages, including healthy volunteers and patients without neurological or psychiatric disease. The cerebrospinal fluid gamma-aminobutyric acid concentration was determined by radiolabelled receptor assay using [3H]gamma-aminobutyric acid. Cerebrospinal fluid gamma-aminobutyric acid was significantly higher in the control group (20s and 30s) than in the groups of subjects in their 50s, 60s, 70s and 80s. There was a significant negative correlation between cerebrospinal gamma-aminobutyric acid concentration and age (p less than 0.01). These data suggest that dysfunction of brain gamma-aminobutyric acid metabolism increases with age, and that the various symptoms caused by abnormal gamma-aminobutyric acid metabolism in the brain are therefore more likely to appear in elderly people.

Adult↗
PubMed1992

[Chronic administration of lisuride hydrogen maleate increases muscarinic acetylcholine receptor binding in aged rat brain].

Changes in the distribution and densities of muscarinic acetylcholine receptors (mACh-R) in young adult and aged rat brain, and the effects of chronic administration of lisuride hydrogen maleate (lisuride) on these changes were studied by in vitro quantitative autoradiography of [3H] quinuclidinyl benzilate binding. mACh-R was relatively higher in the striatum, hippocampus and cerebral cortex in the young adult rats. In contrast, mACh-R binding was markedly reduced in the striatum, accumbens nucleus, amygdaloid nucleus and frontal cerebral cortex of aged rats compared to young adult rats. However, chronic administration of lisuride significantly increased mACh-R binding in the parietal cerebral cortex as well as in the above-mentioned regions in aged rats. This lisuride-induced increase in mACh-R of aged rat brain is considered to have important implications concerning the mechanism of therapeutic efficacy of lisuride.

Aging↗
PubMed1992

[Influence of protein-restricted diet on motor response fluctuations in Parkinson's disease].

The clinical management of Parkinson's disease has been revolutionized by the introduction of levodopa therapy. It has significantly reduced disability and has extended life expectancies of patients with Parkinson's disease. However, motor response fluctuations frequently appear in patients after long-term treatment with levodopa. In this study, we investigated the effect of protein-restricted diet on fluctuations in eight patients with Parkinson's disease who had been receiving long-term levodopa treatment (mean 12.5 years). Two weeks of protein-restricted daytime diet (7.5 g total at breakfast and lunch) was followed by 12.5 g total at breakfast and lunch. At night, high-protein diet (40-50 g at dinner) was offered to the patients in order to maintain total daily protein intake at Japanese standard level. The medication schedule of levodopa and other antiparkinsonian drugs was not changed within 2 weeks after the study was began. Fluctuations were reduced in 7 of the 8 patients. But in only one patient (case 6), dyskinesia and general condition got worse and stopped this therapy. Body weight, serum protein and albumin levels did not change significantly for at least three month after the study was begun in every 6 patients who were examined. Homovanillic acid level of cerebrospinal fluid reduced in every 4 patients who were examined. We concluded that protein-restricted diet during the daytime offers a fascinating technique for the control of motor response fluctuations in patients with Parkinson's disease undergoing long-term levodopa treatment. But this therapy must be indicated carefully. Mechanism of this therapy may has something to do with improvement of dopamine metabolism in the brain.

Adult↗
PubMed1992

Effect of propentofylline on ischemia-induced loss of muscarinic cholinergic receptor binding in the gerbil hippocampus.

Super-delayed loss of muscarinic-1 (M1) receptors and the protective effect of propentofylline on these changes were examined in the gerbil hippocampus after transient ischemia with radioactive pirenzepine. M1 receptors were markedly decreased in the gerbil hippocampus 14 days after transient ischemia. Single administration of propentofylline (20 mg/kg, ip) just after transient ischemia almost completely prevented the ischemia-induced decrease in the number of M1 receptors, and had no effect in sham-operated controls. These findings suggest that one of the therapeutic efficacies of propentofylline is the result of the normalization of the dysfunction of the acetylcholine neuronal system in cerebrovascular disease.

Animals↗
PubMed1991

Long-lasting effect of ceruletide on dyskinesia and monoaminergic neuronal pathways in rats treated with iminodipropionitrile.

In a model of dyskinesia induced by the administration of iminodipropionitrile (IDPN) in the rat, we evaluated the effects of ceruletide, an analogue of cholecystokinin, on behavioral abnormalities and monoaminergic neuronal function. Vertical head twitching in the IDPN-treated animals was inhibited for over 5 h following a single subcutaneous dose of 160 micrograms/kg ceruletide. In animals dosed daily for 2 or 3 days, the number of head twitches at 24 h after the last dose was about one-third of the number before treatment. After repeated daily doses of ceruletide for 6 days, the number of head twitches was reduced to low levels and remained significantly below pretreatment levels until the 4th posttreatment day. These results indicate that the inhibition of dyskinesia by ceruletide was long-lasting. Assays of monoaminergic neurotransmitters and their metabolites in various brain regions indicate that an imbalance between dopaminergic and serotonergic neuronal systems plays a major role in the pathogenesis of the IDPN-induced dyskinesia, i.e. the ratio of (DOPAC+HVA)/5-HIAA was significantly greater in the striatum but significantly smaller in the hippocampus of the IDPN-treated vs normal animals. This initially abnormal ratio of (DOPAC+HVA)/5-HIAA in the striatum and hippocampus of IDPN-treated animals returned to normal following treatment with ceruletide, corresponding with the reduction of the head twitching. The alterations in monoaminergic neuronal function induced by repeated administration of ceruletide persisted for at least 3 days, even though its plasma half-life is several minutes. Ceruletide also exerted a marked effect on monoaminergic neuronal function in the IDPN-treated rats, in contrast to only a slight effect in normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗