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Biomedical subjects

B Bioulac

Publications and source records attributed to B Bioulac.

At least 73 records · Page 4Linked to original sources
PubMed1997

Effects of different schedules of MPTP administration on dopaminergic neurodegeneration in mice.

Although a valuable 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of human Parkinson's disease has been developed, our knowledge of the course of nigral degeneration remains fragmentary. Experimental factors which could possibly influence the destructive process must be taken into account. To evaluate the impact of experimental design, we compared the effects of different schedules of injection of the same cumulative dose of MPTP, in mice, by measuring tyrosine hydroxylase immunoreactivity in the substantia nigra pars compacta. Massive injection of the total dose over 1 day (4 injections of 20 mg/kg) destroyed more dopaminergic neurons than did the long-term daily injections of a lower dose of MPTP (20 injections of 4 mg/kg). This suggests that different schedules of administration of MPTP might induce different mechanisms of neuronal death. These mechanisms need to be better understood if chronic models of intoxication that replicate the evolution of human Parkinson's disease more precisely are to be developed.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1997

Compensatory effects of glutamatergic inputs to the substantia nigra pars compacta in experimental parkinsonism.

The effect of transitory blockage of substantia nigra pars compacta glutamatergic inputs by intracranial injections of kynurenic acid were evaluated in two monkey treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The MPTP protocol was designed to mimic the gradual evolution of human Parkinson's disease. No effects were observed before MPTP treatment or in the first stage of treatment. Once clinical signs appeared, however, motor abnormalities were significantly aggravated by blockage of these inputs (P < 0.001). Conversely, after full Parkinsonism was established, blockage no longer had any behavioural effect. These results confirm the postulated compensatory role of the glutamatergic pathways feeding the substantia nigra pars compacta. This added insight into the physiopathology of the basal ganglia, when compared with previous data on the presymptomatic revelation of experimental Parkinsonism, should help elucidation of the time pattern of evolution of Parkinson's disease.

Animals↗
PubMed1997

Objective measurement of sleepiness in summer vacation long-distance drivers.

The study investigated whether sleepiness at the wheel is a problem in non-commercial drivers going on summer vacation. All drivers, who stopped at a rest area on a large European freeway while one of the interviewers was available, were systematically approached and asked to respond to a questionnaire. All subjects who had driven at least 400 km (240 miles), whose age was between 20 and 46 years of age, and who agreed to participate were asked to undergo a longer investigation that included a short sleep/wake diary describing overall sleep habits during the year, a sleep/wake log covering the days just prior to departure, an analog visual scale indicating sleepiness at time of interview, and a polygraphically monitored two nap sleep test (TNST). A control group was recruited that consisted of subjects of the same age range, normal sleep habits, and normal nocturnal sleep time before administration of the TNST. One hundred and four drivers (2 women) participated between 08:00 and 20:00 h. The total group was subdivided into 6 subgroups based upon the time of day of their investigation (08:00-10:00 h, 10:01-12:00 h, etc.). The control group included 50 men with 50-55% of control subjects, relative to the total number of index-cases, in each subgroup. Eighty-eight percent (n = 92) of studied drivers had experienced acute sleep deprivation within one day prior to departure due to the planned long driving. The TNST demonstrated that, overall, drivers had a significantly shorter sleep latency in nap 1 and nap 2 than controls, had a significantly longer sleep duration in nap 1 and nap 2, and there was a significant correlation between the sleep debt prior to departure and the sleep stage reached during the TNST. It is concluded that the TNST is a test which allows the objective study of sleepiness in drivers without the burden of the multiple sleep latency test. Many drivers are excessively sleepy when making long summer vacation journeys.

Adult↗
PubMed1997

Prevalence and correlates of nocturnal desaturations in a sample of elderly people.

We designed an epidemiological study to estimate the prevalence and correlates of nocturnal desaturations in a sample of elderly subjects from the general population. Sleep-related respiratory disturbances were assessed by questionnaire and MESAM IV (MADAUS electronic sleep apnoea monitor) ambulatory monitoring. An oxygen desaturation index (ODI), oxygen desaturation being defined as a decrease in SaO2 of or exceeding 4%, was then computed from these data. An oxygen desaturation index > or = 10 was observed in 27.0% of the 293 subjects studied (mean age 76.6+/-5.7 y, median=75 y, min.=69, max.=99), an oxygen desaturation index > or = 30in 4.4%. Multivariate analysis identified as correlates to an oxygen desaturation index > or = 10: male gender (OR=1.80; P=0.04), a high body mass index (BMI) in men (OR=1.20 per kg m2; P=0.0009), and advanced age in women (OR=1.09 per y; P=0.02). A positive association was found between loud snoring (OR=1.75; P=0.06) and an oxygen desaturation index > or = 10. However, there was no statistically significant relationship between an oxygen desaturation index > or = 10 and either daytime somnolence (OR=1.50; P=0.19) or trouble getting to sleep (OR=0.59; P=0.09). We found no significant relationship in our sample between oxygen desaturation index and arterial hypertension or cardiac dysrhythmia. Previous studies on younger populations have reported different results. It may well be the advanced age of our sample that explains these inconsistencies. For the elderly persons we studied our results underline the relatively high prevalence of sleep-related respiratory disturbances. However, these may be of less consequence than in younger populations.

Aged↗
PubMed1997

High-frequency stimulation of the globus pallidus internalis in Parkinson's disease: a study of seven cases.

The effectiveness of ventroposterolateral pallidotomy in the treatment of akinesia and rigidity is not a new discovery and agrees with recent investigations into the pathogenesis of Parkinson's disease, which highlight the role played by the unbridled activity of the subthalamic nucleus (STN) and the consequent overactivity of the globus pallidus internalis (GPi). Because high-frequency stimulation can reversibly incapacitate a nerve structure, we applied stimulation to the same target. Seven patients suffering from severe Parkinson's disease (Stages III-V on the Hoehn and Yahr scale) and, particularly, bradykinesia, rigidity, and levodopa-induced dyskinesias underwent unilateral electrode implantation in the posteroventral GPi. Follow-up evaluation using the regular Unified Parkinson's Disease Rating Scale has been conducted for 1 year in all seven patients, 2 years in five of them, and 3 years in one. In all cases high-frequency stimulation has alleviated akinesia and rigidity and has generally improved gait and speech disturbances. In some cases tremor was attenuated. In a similar manner, the authors observed a marked diminution in levodopa-induced dyskinesias. This could be an excellent primary therapy for younger patients exhibiting severe bradykinesia, rigidity, and levodopa-induced dyskinesias, which would allow therapists to keep ventroposterolateral pallidotomy in reserve as a second weapon.

Adult↗
PubMed1996

High frequency stimulation of the internal Globus Pallidus (GPi) simultaneously improves parkinsonian symptoms and reduces the firing frequency of GPi neurons in the MPTP-treated monkey.

The firing pattern of the neurons of the internal Globus Pallidus (GPi) is greatly disturbed in Parkinson's disease. Surgical lesion or high frequency stimulation (HFS) of the GPi reduces parkinsonian rigidity and akinesia. We evaluated in this study the effects of HFS of the GPi on the firing pattern of its neurons. Extracellular recordings were carried out under three types of experimental conditions in rhesus monkeys, normal state, after MPTP treatment and during HFS of the GPi. After intracarotidian MPTP injection, the firing rate of GPi cells increased significantly. During HFS, MPTP-induced parkinsonian motor symptoms clearly improved correlatively with a significant decrease in the firing rate of GPi cells in the stimulated area. HFS restored a firing frequency similar to that in normal animals and, unexpectedly, did not completely block neuronal activity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1996

Responses of substantia nigra pars reticulata neurons to intrastriatal D1 and D2 dopaminergic agonist injections in the rat.

Extracellular neuronal recordings were performed in the substantia nigra pars reticulata (SNr) of normal and 6-hydroxydopamine (6-OHDA)-lesioned rats during intrastriatal D1 and D2 dopaminergic-agonist injections. Three types of responses were observed, inhibition, excitation and/or regularization of neuronal discharge patterns. In normal rats, variable responses were observed after D2 injections and a predominance of inhibition after D1 injections. In lesioned rats, the percentage of neurons inhibited and that of neurons regularized increased following D2 injections. During sequential intrastriatal D1 and D2 agonist injections, a response to both dopaminergic agents was observed in 22.5% and 55.5% of SNr neurons in normal and lesioned rats, respectively. Our data suggests that the physiological relevance of direct and indirect pathways convergence upon a given SNr target neuron depends on their respective synaptic weight, the influence of surrounding SNr neurons and the state of dopamine depletion.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1996

Alleviation of experimental hemiparkinsonism by high-frequency stimulation of the subthalamic nucleus in primates: a comparison with L-Dopa treatment.

Experimental studies in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys have shown that akinesia and rigidity are linked to a hyperactivity of glutamatergic subthalamic nucleus neurons and that the lesion of this nucleus can ameliorate parkinsonian motor signs. In our study, high-frequency stimulation applied at the subthalamic level was performed on two Macaca mulatta monkeys rendered hemiparkinsonian by unilateral infusion of MPTP. Its effects on rigidity and bradykinesia have been quantified. The results exhibit an important alleviation of both symptoms during the application of subthalamic stimulation comparable to that obtained during L-Dopa treatment, but without the appearance of abnormal movements such hemiballism or dyskinesia. Our data show that subthalamic stimulation has a beneficial effect on experimental parkinsonian rigidity and bradykinesia and suggests a new therapy approach for the treatment of Parkinson's disease by using subthalamic high-frequency stimulation instead of L-Dopa treatment.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1996

Determinants of sleepiness in automobile drivers.

Governmental agencies do not systematically investigate the presence of daytime sleepiness as a determinant of driving accidents. We surveyed automobile drivers traveling on summer vacations and driving long distances on a European highway. We evaluated their subjective daytime sleepiness while driving and any sleep deprivation just prior to departure. Five-hundred sixty-seven automobile drivers (mean age 37.7 +/- 11 years) were interviewed at a roadside rest-stop. Questions covered the sleep/wake schedule during the year, sleep habits, and the presence of symptoms frequently associated with sleep-disordered breathing. Sleep behavior just prior to departure was compared to the usual sleep schedule during the year. Fifty percent of the responders had a sleep restriction just prior to departure (mean -203 minutes) compared to usual total sleep time during the year; 10% had no nocturnal sleep prior to departure. Drivers younger than 30 years were significantly more acutely sleep deprived than other drivers. Economic migrants (subjects with low economic status) also experienced significant acute sleep restriction.

Accidents, Traffic↗
PubMed1996

A randomised, double blind, placebo controlled trial of botulinum toxin in the treatment of spastic foot in hemiparetic patients.

OBJECTIVE: To confirm the apparent effectiveness of botulinum toxin (BTX) in hemiparetic patients with ankle plantar flexors and foot invertor spasticity. METHODS: Twenty three hemiparetic patients with spasticity of the ankle plantar flexors and foot invertors were included in a randomised double blind, placebo controlled study with BTX. Patients were examined on days 0, 30, 90, and 120 and received one injection of BTX and one of placebo in a random order at day 0 and day 90. RESULTS: Patients reported a clear subjective improvement in foot spasticity after BTX (P = 0.0014) but not after placebo. Significant changes were noted in Ashworth scale values for ankle extensors (P < 0.0001) and invertors (P = 0.0002), and for active ankle dorsiflexion (P = 0.0001). Gait velocity was slightly but not significantly (P = 0.0731) improved after BTX injections. The severity of spasticity did not modify treatment efficacy, but BTX was less effective in patients with longer duration of spasticity (P = 0.0081). CONCLUSION: The efficacy of BTX injections in the treatment of spastic foot suggests that BTX may be particularly useful during the first year after a stroke.

Adult↗
PubMed1995

Activity of area 5 neurons in monkeys during arm movements: effects of dentate nucleus lesion and motor cortex ablation.

Area 5 movement-related neurons were recorded in two trained monkeys respectively before and after (i) bilateral lesion of the dentate nucleus (DN), (ii) ablation of the motor cortex (area 4). DN lesion does not modify the proportion of early (command) and late (somaesthetic) neuronal changes. It does, however, increase both cellular and behavioural reaction times. The ablation of area 4 induces a clear-cut increase in the number of early neuronal changes during the period of recovery from arm palsy. These results show that: (i) the neocerebellum enhances the excitability of area 5 movement-related neurons; (ii) area 5 may compensate for the deficiency in area 4 by unmasking silent neurons and thereby subserves rehabilitation mechanisms.

Animals↗
PubMed1995

Reduction of apomorphine-induced rotational behaviour by subthalamic lesion in 6-OHDA lesioned rats is associated with a normalization of firing rate and discharge pattern of pars reticulata neurons.

The effect of subthalamic nucleus (STh) lesion on apomorphine-induced rotational behaviour and unit activity of substantia nigra pars reticulata (SNr) neurons was studied in normal, sham-control and unilateral 6-OHDA-lesioned rats [SN pars compacta (SNc)-lesioned]. In the latter, contraversive rotational behaviour was greatly reduced by an additional ipsilateral STh lesion. A moderate ipsiversive rotation was observed in rats with a single STh lesion. Concurrently, SN unit extracellular recordings were performed in age-matched normal rats, sham-controls for both lesions, STh-lesioned rats, SNc-lesioned rats, and SNc-lesioned rats with an ipsilateral STh lesion (SNc+STh-lesioned). Pars reticulata neurons had a higher mean firing rate in SNc-lesioned rats than in control rats. Furthermore, 68% of SNr neurons in SNc-lesioned rats had a tonic discharge pattern (against 92.3% in control rats) and 32% a mixed or bursting pattern. After STh lesion, a clear decrease in SNr firing rate was observed in SNc-lesioned rats. Moreover, STh lesion improved interspike interval regularity and decreased the occurrence of bursting patterns. In rats with a single STh lesion, the firing rate was no different from that of the sham-controls but the discharge pattern was more regular. These data show that STh lesion decreased apomorphine-induced rotational behaviour in dopamine-depleted animals. This effect could be related to the suppression of the excitatory effect of STh efferents on the SNr neurons. STh lesion both counterbalanced the increased activity of SNr neurons and regularized their discharge pattern.

Animals↗
PubMed1995

Lateralization of prefrontal activation during internal mental calculation: a functional magnetic resonance imaging study.

1. Functional magnetic resonance imaging (fMRI) at 1.5 T was used to investigate the lateralization of prefrontal cortex activity during internal mental calculation in 16 human volunteers (8 right-handed and 8 left-handed). Subjects were asked to perform two different tasks: 1) a serial subtraction of prime numbers and 2) a control task in which they mentally recited numbers. 2. Signal modifications were regularly observed in the prefrontal cortex (Brodmann's area 46) during the serial subtraction of prime numbers, whereas the number listing task poorly activated the same areas. 3. In right-handed subjects, activation was clearly lateralized in the left dorsolateral prefrontal cortex, whereas a frequent bilateral activation was found in left-handed subjects. 4. We conclude that prefrontal activation during mental calculation is lateralized in a manner similar to that reported during linguistic tasks, i.e., a clear lateralization in right- but not in left-handed subjects.

Adult↗
PubMed1993

Reversal of rigidity and improvement in motor performance by subthalamic high-frequency stimulation in MPTP-treated monkeys.

In Parkinson's disease the loss of dopaminergic neurons in the substantia nigra is associated with global disorganization of basal ganglia activity and, in particular, with increased activity of the excitatory glutamatergic neurons of the subthalamic nucleus. Recent experimental studies have shown that parkinsonian symptoms can be alleviated by selective lesioning of the subthalamic nucleus in monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We measured the effect of high-frequency stimulation of the subthalamic nucleus in two unilaterally MPTP-treated monkeys in order to determine whether it was possible to obtain reversible, gradual and controllable functional impairment of this structure. Clinical, mechanographic and electromyographic results demonstrate that this technique can alleviate parkinsonian rigidity and bradykinesia without causing dyskinesia or hemiballismus. This study supports the hypothesis that the subthalamic nucleus and its excitatory projections have an important role in the mechanisms sustaining the expression of parkinsonian motor changes, and suggests that high-frequency stimulation of the subthalamic nucleus could be included in treatment for parkinsonism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1992

MPTP induced hemiparkinsonism in monkeys: behavioral, mechanographic, electromyographic and immunohistochemical studies.

A single infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) into the right internal carotid artery of Macaca mulatta monkeys resulted in akinesia and rigidity of the contralateral limb. The immunohistochemical study revealed a dramatic reduction in the number of TH-immunoreactive cells in the substantia nigra of the infused side (70-81%). After unilateral MPTP-treatment movement parameters and EMG activity were altered; the agonist muscle developed increased EMG activity associated with a shift of antagonist muscle activity. These results confirm that hemiparkinsonian monkeys are a valuable model of parkinsonism which can be useful in studies of movement disorder physiology and therapy of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗