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Biomedical subjects

A Benazzouz

Publications and source records attributed to A Benazzouz.

At least 55 records · Page 3Linked to original sources
PubMed1997

Chronic administration of DL-allyl-glycine into the neostriatum, disorganises the firing modes of the nigral dopaminergic neurons in the rat.

Nigral dopaminergic (DA) neurons have been reported to fire according to three modes: very regular (pacemaker 42%) irregular (random 46%) and bursty (12%). The switch from simple spiking mode (pacemaker or random) to bursty firing would correspond to an increase in DA release necessary for the performance of a new motor act. As nigral DA cells are impinged upon by a high percentage of GABAergic afferents we blocked striatal GABAergic output neurons by chronic administration into the neostriatum of allyl-glycine, a glutamic acid decarboxylase (GAD) inhibitor. After treatment, rats presented hyperkinesia and hypertonia on the injected side and recordings showed a drastic change in the percentage distribution of nigral DA cell discharge patterns; 85% were 'random', 12% 'pacemaker' and 3% bursty. Such a disturbance, by impeding adapted DA release, may account for the hyperkinetic and dystonic disorders observed.

Animals↗
PubMed1996

Abnormal involuntary movements induced by subthalamic nucleus stimulation in parkinsonian patients.

Chronic electrical subthalamic nucleus (STN) stimulation is under investigation for alleviating parkinsonian symptoms. STN alterations may carry the risk of provoking abnormal involuntary movements (AIMs). We took advantage of the reversibility of the stimulation technique to assess the possibility of inducing AIMs, using different electrical variables with or without concomitant levodopa intake. Above a given threshold voltage, stimulation could induce contralateral distal mobile AIMs or hemiballism in the off-drug condition in two patients. AIMs occurred after a latency that varied from a few minutes up to several hours after switching on the stimulator. Hemiballism immediately disappeared upon switching off the stimulator. In these patients, levodopa had never provoked that type of AIMs before surgery. Levodopa-induced AIMs were not modified by electrical stimulation, but off-phase dystonia disappeared in one patient. Stimulation of the STN induced AIMs that resembled both those observed following spontaneous lesions of the STN and levodopa-induced diphasic AIMs in parkinsonian patients. As electrical stimulation provoked AIMs and antiparkinsonian benefit occurred with different electrical variables and different timing, the mechanisms responsible for these two effects could be distinct.

Antiparkinson Agents↗
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

Subthalamic nucleus lesion in rats prevents dopaminergic nigral neuron degeneration after striatal 6-OHDA injection: behavioural and immunohistochemical studies.

Several studies have shown that antagonists of N-methyl-D-aspartate receptors provide protection of the dopaminergic nigrostriatal pathway in animal models of Parkinson's disease. Since the substantia nigra compacta receives a moderate glutamatergic innervation from the subthalamic nucleus, we tried to determine whether subthalamic nucleus lesion could prevent the toxicity of the selective dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA). Experiments were carried out on four groups of rats. Group 1 (n = 10) received a unilateral injection of 6-hydroxydopamine in the striatum and group 2 (n = 10) received kainic acid in the subthalamic nucleus. Group 3 (n = 10) received an injection of kainic acid in the subthalamic nucleus and 1 week later an injection of 6-OHDA in the striatum. Group 4 (n = 5) received the same treatment but kainic acid was replaced by saline. Apomorphine induced an ipsilateral rotation in rats of groups 2 and 3 and a contralateral rotation in rats of groups 1 and 4. The number of tyrosine hydroxylase-immunoreactive cells in the pars compacta of the substantia nigra was not significantly decreased on the side ipsilateral to 6-OHDA striatal injection in rats of groups 1 and 4. These results show that subthalamic nucleus lesion provides neuroprotection of the dopaminergic nigrostriatal pathway against 6-OHDA toxicity and opens a new way for slowing or stopping the progression of Parkinson's disease.

Animals↗
PubMed1996

Chronic electrical stimulation of the ventralis intermedius nucleus of the thalamus as a treatment of movement disorders.

Tremor was suppressed by test stimulation of the thalamic ventralis intermedius (VIM) nucleus at high frequency (130 Hz) during stereotaxy in nonanesthetized patients suffering from Parkinson's disease or essential tremor. Ventralis intermedius stimulation has since been used by the authors over the last 8 years as a treatment in 117 patients with movement disorders (80 cases of Parkinson's disease, 20 cases of essential tremor, and 17 cases of various dyskinesias and dystonias including four multiple sclerosis). Chronic electrodes were stereotactically implanted in the VIM and connected to a programmable stimulator. Results depend on the indication. In Parkinson's disease patients, tremor, but not bradykinesia and rigidity, was selectively suppressed for as long as 8 years. Administration of L-Dopa was decreased by more than 30% in 40 Parkinson's disease patients. In essential tremor patients, results were satisfactory but deteriorated with time in 18.5% of cases, mainly for patients who presented an action component of their but deteriorated with time in 18.5% of cases, mainly for patients who presented an action component of their tremor. In other types of dyskinesias (except multiple sclerosis), results were much less favorable. Fifty-nine patients underwent bilateral implantation and 14 other patients received implantation contralateral to a previous thalamotomy. Thirty-seven patients (31.6%) experienced minor side effects, which were always well tolerated and immediately reversible. Three secondary scalp infections led to temporary removal of the implanted material. There was no permanent morbidity. This tremor suppression effect could be due to the inhibition or jamming of a retroactive loop. Chronic VIM stimulation, which is reversible, adaptable, and well tolerated even by patients undergoing bilateral surgery (74 of 117 patients) and by elderly patients, should replace thalamotomy in the regular surgical treatment of parkinsonian and essential tremors.

Electric Stimulation Therapy↗
PubMed1995

Riluzole prevents MPTP-induced parkinsonism in the rhesus monkey: a pilot study.

Previous studies have shown that riluzole (2-amino-6-trifluoromethoxy-benzothiazole), a drug which interferes with glutamate neurotransmission, has a neuroprotective action in rodent models of global and focal cerebral ischemia. In this pilot study, the protective and palliative effects of riluzole have been examined using an animal model of Parkinson's disease. Two monkeys were rendered hemiparkinsonian by one intracarotid injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and motor signs were evaluated using clinical examination and electromyographic recordings. When riluzole (4 mg/kg) was administered before the injection of MPTP, parkinsonian motor symptoms, in particular bradykinesia and rigidity, were absent. When injected daily in one monkey which presented stable motor symptoms, bradykinesia and rigidity were significantly reduce d. Riluzole pretreatment induced a persistent increase in dopamine turnover when compared to MPTP alone. Thus, a possible neuroprotection and a facilitation of dopamine release may explain the behavioural effects reported with riluzole treatment. These preliminary results suggest that riluzole could possess neuroprotective and palliative effects in a primate model of Parkinson's disease.

Animals↗
PubMed1995

Responses of substantia nigra pars reticulata and globus pallidus complex to high frequency stimulation of the subthalamic nucleus in rats: electrophysiological data.

High frequency stimulation of the subthalamic nucleus (STN-HFS) has been shown to reverse parkinsonian motor symptoms in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. We have studied the effect of STN-HFS on the spontaneous activity of the substantia nigra pars reticulata (SNr), entopeduncular nucleus (EP) and globus pallidus (GP) in rats. STN-HFS induced a decrease in activity of 91% of SNr cells, a suppression of activity in 80% of EP cells and an activation of 100% of GP recorded cells. These results show that STN-HFS exerts an inhibitory influence on the basal ganglia output structures similar to that obtained by STN lesion.

Animals↗
PubMed1995

Effect of parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation.

In monkeys rendered parkinsonian, lesions and electrical stimulation of the subthalamic nucleus reduce all major motor disturbances. The effect of electrical stimulation of the subthalamic nucleus was assessed in three patients with disabling akinetic-rigid Parkinson's disease and severe motor fluctuations. Quadripolar electrodes connected to a pulse generator were implanted in the subthalamic nuclei on both sides. Patients were evaluated with the unified Parkinson's disease rating scale and timed motor tests. 3 months after surgery, activities of daily living scores had improved by 58-88% and motor scores by 42-84%. This improvement was maintained for up to 8 months in the first patient operated upon. One patient was confused for 2 weeks after surgery, and another developed neuropsychological impairment related to a thalamic infarction which improved over 3 months. In one patient, stimulation could induce ballism that was stopped by reduction of stimulation. This is the first demonstration in human beings of the part played by the subthalamic nuclei in the pathophysiology of Parkinson's disease.

Electric Stimulation Therapy↗
PubMed1995

Bilateral subthalamic nucleus stimulation for severe Parkinson's disease.

Subthalamic nucleus (STN) lesions or high-frequency stimulations could improve parkinsonian symptoms in monkeys treated by MPTP. We have applied the procedure of chronic stimulation to the STN in severely disabled parkinsonian patients. This article presents the case of the first patient operated on bilaterally. Bilateral STN stimulation has greatly improved akinesia and rigidity. The benefit was maintained < or = 15 months after surgery. Unilateral stimulation induced motor effects mainly in contralateral limbs. Further studies are needed to evaluate the value of this procedure in the treatment of Parkinson's disease.

Antiparkinson Agents↗
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

Lysolecithin-induced demyelination in primates: preliminary in vivo study with MR and magnetization transfer.

PURPOSE: To study bystander demyelination in multiple sclerosis with an experimental in vivo model of toxic demyelination. METHODS: Toxic demyelinating lesions were created in two monkeys by injection of lysophosphatidylcholine in the centrum semiovale. Follow-up was done clinically and with serial MR studies, including T2-weighted and gadolinium-enhanced T1-weighted images and measurement of magnetization transfer ratio, until the animals were killed at days 14 and 34, respectively. Light and electron microscopy analysis was compared with MR data. RESULTS: Interval measurement of magnetization transfer ratio during the course of the experiment revealed a maximum decrease at day 7 to day 8, associated with the greatest clinical manifestations. The lowest values of magnetization transfer ratio correlated with histopathologic findings of myelin and axon destruction. Magnetization transfer ratio measurements appear to be sensitive to macromolecular destruction and specifically to membrane disorganization. At no time was gadolinium enhancement observed in this model of toxic demyelination. CONCLUSION: Preliminary results of this study indicated that magnetization transfer is a good technique to follow in vivo matrix destruction in brain parenchyma lesions. The results suggest also that phases of toxic demyelination in multiple sclerosis might not show gadolinium enhancement. Differentiation between demyelinating activity and associated inflammation in multiple sclerosis lesions should be considered in further in vivo work.

Animals↗
PubMed1994

Acute and long-term effects of subthalamic nucleus stimulation in Parkinson's disease.

In animal models of Parkinson's disease (PD), it is postulated that the excessive output from the subthalamic nucleus (STN) plays a critical role. Selective lesions or high frequency electrical stimulation of the STN can alleviate parkinsonian symptoms in MPTP-treated monkeys. We decided to carry out STN stimulation in patients suffering from severe akinetic forms of PD. After approval of the institutional ethical committee, we operated on a parkinsonian patient aged 51, suffering for 8 years from a strongly disabling akinetorigid form of PD, complicated by an on-off effect (Hoehn and Yahr stage 5 in the worst-off motor phase). Stereotactic surgery was done on one side under local anesthesia. The theoretical target was chosen according to stereotactic atlases, based on ventriculographic landmarks such as anterior and posterior commissures (AC and PC). The final position of the chronic electrodes was optimized using electrophysiological recording and stimulation along with clinical assessment and surface EMG of agonist and antagonist muscles of the examined limbs. A spontaneous increase in neuronal activity was recorded in an area located 2-4 mm under the level of the intercommissural plane, 10 mm from the midline, at mid-distance between AC and PC. Within the same place, a 130-Hz stimulation induced acute and reversible akinesia alleviation mainly on the contralateral limbs, comparable to that obtained with dopaminergic drugs. No dyskinesia, such as hemiballism, was induced by introduction of electrodes or by stimulation. Then a long-term quadripolar DBS Medtronic electrode was inserted in this area. Studies of the effects of chronic stimulation were extensively performed to determine the best spatiotemporal and electrical stimulation variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Electric Stimulation Therapy↗
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↗
PubMed1993

[Effects of the stimulation of the subthalamic nucleus in Parkinson disease].

In Parkinson's disease, experimental studies favour a neuronal hyperactivity of the subthalamic nucleus. We carried out a subthalamic nucleus electrical stimulation in a patient aged 51, suffering for 8 years from a severe akineto-rigid form of Parkinson's disease, complicated with an on-off effect. Stereotaxic surgery was done under local anaesthesia on one side. Within the theoretical target, a 130 Hz stimulation induced akinesia alleviation mainly on the contralateral limbs. No abnormal movement was noticed. Then a long-term quadripolar DBS Medtronic electrode was inserted in that area. The study of the effects of chronic stimulation is in progress to determine the best temporal and electrical stimulation variables.

Electric Stimulation Therapy↗
PubMed1992

Gradient expression of Cdx along the rat intestine throughout postnatal development.

Rat genomic DNA was isolated by homology with Cdx1, a murine homeogene selectively expressed in intestinal cells of endodermal origin. Southern blot analysis indicated that the rat genome contains a single or a small number of closely related Cdx gene(s). A major 1.7 kb Cdx mRNA was detected in neonate, suckling and adult rats whereas a 6.5 kb mRNA was restricted to sucklings and adults. Both transcripts showed decreasing concentration from the colon towards the proximal part of the small intestine. No obvious correlation could be established with the patterns of expression of transcripts corresponding to markers of cell proliferation and cell differentiation during postnatal development.

Aging↗
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↗