ISSN:0014-3022    

DOI:10.1159/000119533

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Selective and characteristic neuron damage induced by acromelic acid, a potent kainate analogue, was investigated in comparison to a kainate-induced one. A single systemic injection of acromelic acid A caused behavioral and pathological effects distinct from those seen after systemic kainate. There was an initial marked tonic extension of the rat hindlimb, often followed by convulsions and, in surviving rats, by a transient flaccid paralysis and ultimately, a persistent spastic paraplegia. Pathological examination suggested specific lesions of interneurons in the lower spinal cord with little or no damage to the hippocampal neurons preferentially affected by systemic kainate. Another agonist for kainate-type receptors, which is not a kainoid, demonstrated neurological symptoms and neuron damage quite similar to those of kainate. Pharmacological actions of our newly developed agonists for metabotropic glutamate receptors were described with special reference to kainate excitotox-icity. Intraventricular DCG-IV, a new agonist, caused selective neuron damage in the cingulate cortex and the hippocampal subiculum at relatively high doses, but other agonists did not cause neuron damage in the rat. DCG-IV considerably alleviated the kainate-induced limbic seizures. At relatively low doses, DCG-IV protected some kinds of neurons in the hippocampal CA3 and the amygdala against kainate neurotoxicity, when intraventricularly injected to the rat. These new agonists would provide useful probe for elucidating the mechanism underlying neuron damage induced by kainate-type agonists.

ISSN:0014-3022    

DOI:10.1159/000119534

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Plasminogen (PGn), which was identified as a secretory product from microglia, increased dopamine uptake and the number of tyrosine-hydroxylase-expressing neurons in cultured rat mesencephalic neurons. 125I-PGn was found to bind specifically much more to mesencephalic neurons compared to other glial cells. The binding was also recognized in plasma membrane prepared from embryonic rat brain. Furthermore, ligand blotting analysis revealed that 125I-PGn binds to a 45-kD protein in plasma membrane. These results suggest that PGn-dependent neurotrophic effects may be induced through the specific binding of PGn to the 45-kD PGn-receptor-like protein in neurons.

ISSN:0014-3022    

DOI:10.1159/000119536

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

L-Dopa pioneered the symptomatic therapy of Parkinson’s disease. While this treatment proved effective in the treatment of parkinsonian akinesia, rigidity and tremor, prolonged L-dopa treatment was often noted to result in dyskinesia, psychosis and ‘on-off phenomena. This increasing disability of L-Dopa-treated parkinsonian patients, however, is not correlated with the duration of L-dopa treatment. Mortality due to Parkinson’s disease has decreased significantly after the introduction of L-dopa treatment. The development of Dl-selective dopamine agonists and the introduction of neuroprotective rather than symptomatic therapy are required for treating Parkinson’s

ISSN:0014-3022    

DOI:10.1159/000119537

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Recent studies have suggested that free radicals play a key role in the progression of Parkinson’s disease (PD). Although levodopa is the most effective therapeutic agent in the treatment of PD and has improved the quality of life and increased life expectancy, its beneficial effects are not permanent. Long-term treatment with levodopa produces a variety of side effects in patients with PD. We have previously reported that levodopa may accelerate the progression of PD in certain patients. To determine whether neuronal damage can be caused by levodopa overdoses, we estimated the effects of levodopa on free radical formation. Electron spin resonance spectrometry showed that levodopa oxidation produced levodopa radicals. Furthermore, chronic administration of levodopa increased thiobarbituric acid-reacting substances (TBARS) in various brain regions of 6-hydroxydopamine (6-OHDA; i.c.v.)-pretreated mice, although levodopa administration in control mice had no effect on TBARS. These results indicate that high dose levodopa accelerates neuronal degeneration in some parkinsonian brains. We then evaluated the protective effects of bromocriptine on striatal dopaminergic neurons, with determination of dopamine (DA) and its metabolites as markers. Pretreatment of bromocriptine completely protected mice against the decreases in striatal DA and its metabolites induced by intracerebroventricular injection of 6-OHDA, while levodo-pa/carbidopa had no protective effects. Furthermore, in an in vitro system that generated "OH from FeSO4-H2SO4, bromocriptine dose-dependently scavenged ‘OH. These findings clearly indicate that bromocriptine has neuroprotective effects against neurotoxins such as 6-OHDA, probably due in part to its free radical scavenging activity. They further indicate that the early introduction of bromocriptine to PD therapy is superior to treatment with levodopa alone. Combination therapy with a DA agonist such as bromocriptine and low doses of levodopa are likely to create a better balance between D2 and Dl receptors, and to maintain normal DA neurotransmission for longer peri

ISSN:0014-3022    

DOI:10.1159/000119538

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

A 7-year nationwide study of bromocriptine monotherapy and combination therapy with bromocriptine and levodopa in Parkinson’s disease is reported. Of 22 patients who had been on bromocriptine monotherapy for 7 years (group B), 16 remained improved or remained in the same stages of Hoehn and Yahr, and no wearing-off phenomenon or dyskinesia was observed. In another 56 patients who were started on bromocriptine alone, but in whom combination therapy with levodopa was instituted at some time in the 7 years (group BL), disease progressed faster than in group B. A wearing-off phenomenon and dyskinesia occurred in 34% and 5.4% of the patients, respectively. These manifestations appeared only after initiation of levodopa. The favorable course of group B suggests possible neuroprotective effects of bromocriptine or may be due to the inevitable selection of patients who had a favorable course originall

ISSN:0014-3022    

DOI:10.1159/000119539

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Since monoamine oxidase is an enzyme catalyzing bioactive monoamines, inhibitors of monoamines are expected to prolong the activity of monoamines in tissue. Monoamine oxidase type B is an active form in brain, and its preferential substrate is dopamine that is the most constantly reduced monoamine in Parkinson’s disease brain. Therefore, it is natural to expect that monoamine oxidase inhibitors, deprenyl or lazabemide, could exhibit beneficial effects on parkinsonism, i.e. symptomatic effects. This short review summarizes characteristics of monoamine oxidase from biochemical and pharmacological points, and then briefly mentions the situation of clinical evaluation studies of deprenyl and lazabemide in terms of antiparkinsonian effects in Japa

ISSN:0014-3022    

DOI:10.1159/000119540

出版商:S. Karger AG    

年代:1994

数据来源: Karger

ISSN:0014-3022    

DOI:10.1159/000119541

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

A number of cortical and subcortical areas are involved in the control of sac-cades and smooth pursuit, and lesions affecting these areas result in various ocular motor syndromes. Most of these syndromes are relatively subtle and have to be ascertained using recordings, because other brain areas may largely take over the function of a damaged area. Anterior cortical, posterior cortical, large and bilateral cortical, subcortical and degenerative cerebral lesions are successively reviewed. In the anterior part of the cerebral hemisphere, the frontal eye field (FEF), supplementary eye field (SEF) and prefrontal cortex (PFC), i.e area 46 of Brodmann, control eye movements. The FEF appears to be principally involved in the control of intentional saccades, in particular those made with a retinotopic reference system, and in smooth pursuit. The SEF could control saccades made with a spatiotopic reference system, and sequences of saccades (requiring a temporal working memory). The PFC could control the inhibition of unwanted reflexive saccades, and be involved in spatial memory used for programming all types of memory-guided saccades. In the posterior part of the cerebral hemisphere, the parietal eye field (PEF) is involved in the triggering of reflexive visually guided saccades, and the middle temporal (MT) and medial superior temporal (MST) areas in smooth pursuit. Acute and large unilateral lesions usually result in transitory ipsilateral conjugate eye deviation. Bilateral lesions affecting both the FEF and the PEF result in severe saccade and smooth-pursuit paresis, whereas bilateral posterior temporoparietal lesions result in Balint’s syndrome, consisting of both eye movement and visual-attention abnormalities. Subcortical lesions also result in various eye movement abnormalities, which have been little documented to date. Lastly, degenerative cerebral diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, progressive supranuclear palsy and corti-cobasal degeneration result in more or less severe eye movement disturbances. Eye movement recordings may contribute to early differential diagnosis of some of these degenerative d

ISSN:0014-3022    

DOI:10.1159/000117025

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

We investigated the presence of duplication in chromosome 17p11.2 in 4 individuals with sporadic Charcot-Marie-Tooth disease (CMT 1) and 1 isolated case where a definite differential diagnosis between CMT 1 and Dejerine-Sottas disease was not achieved. The 5 affected cases and their parents and relatives were submitted to a complete clinical, neurophysiologic and genetic evaluation. A sural nerve biopsy was performed in all the isolated patients. Paternity was tested and confirmed. The presence of DNA duplication was detected in all the sporadic cases and was absent in all parents and relatives, thus confirming that a de novo dominant mutation is commonly present also in patients without a familial history and that there is a practical relevance of the genetic study in distinguishing isolated cases of CMT 1 from other forms of hereditary motor and sensory neuropathies or demyelinating neuropathies.

ISSN:0014-3022    

DOI:10.1159/000117026

出版商:S. Karger AG    

年代:1994

数据来源: Karger