Biomedical subjects

Wassilios Meissner

Publications and source records attributed to Wassilios Meissner.

25 records · Page 2Linked to original sources

PubMed2003

Deep brain stimulation in dystonia.

Renewed interest in stereotaxy for dystonia followed the introduction of deep brain stimulation (DBS) in Parkinson's disease and essential tremor in the 1990s. DBS evolved from ablative surgery, which was applied with varying results in the 1950s in patients with movement disorders such as Parkinson's disease, essential tremor and dystonia. The present review summarizes the current knowledge on clinical aspects of DBS in dystonia (Dec. 2002). Excellent results have been achieved in dystonic patients carrying a mutation in the DYT1 gene with improvements up to 90 %. Similar results may also be obtained in patients with idiopathic generalized dystonia, myoclonus-dystonia syndrome, and tardive dystonia. Substantial improvement has been observed in patients with focal dystonia (for instance cervical dystonia). Patients with secondary dystonia often display a lesser and more variable degree of improvement. Long-term studies are warranted to assess both motor and neuropsychological sequelae of DBS in dystonia. Furthermore, the optimal target for different dystonic disorders remains to be determined, although the globus pallidus internus has currently emerged as the most promising target for dystonia.

Dystonia↗

PubMed2003

Compensatory regulation of striatal neuropeptide gene expression occurs before changes in metabolic activity of basal ganglia nuclei.

Compensatory mechanisms delay the appearance of parkinsonian symptoms. However, both the order of appearance and potential interactions of compensatory mechanisms acting within the nigrostriatal pathway as well as inside and outside the basal ganglia are not clear. We hypothesize that, after the striatal dopaminergic homeostasis breakdown, a modification in the expression of several striatal markers (neuropeptide precursors and dopamine receptors) may occur before a change in the activity of both globus pallidus (GP) and substantia nigra pars reticulata (SNr) in response to a partial nigrostriatal lesion. The present data show, in MPTP-treated mice, that preproenkephalin-A and preprotachykinin mRNA expression and D(3) receptor binding are modified without changes in cytochrome oxidase metabolic activity in both GP and SNr, respectively. These changes in neuropeptide expression would compensate for the dopamine depletion-induced changes in inhibitory GABAergic input from the striatum to GP and SNr. It also indicates that nondopaminergic compensatory mechanisms inherent to the basal ganglia are activated before those residing outside the basal ganglia.

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

PubMed2003

High-frequency stimulation of the subthalamic nucleus enhances striatal dopamine release and metabolism in rats.

High-frequency stimulation of the subthalamic nucleus is believed to exert its main effects via the basal ganglia output structures. Previously, we have shown a concomitant increase in striatal dopamine (DA) metabolites in normal and 6-hydroxydopamine-lesioned rats. The present study was designed to determine whether this increase in striatal DA metabolites reflects enhanced intraneuronal DA turnover or, alternatively, is due to increased DA release with subsequent rapid and efficient reuptake and/or metabolism. Thus, high-frequency stimulation of the subthalamic nucleus was performed in normal rats after inhibition of DA reuptake, metabolism or DA depletion. Extracellular levels of striatal DA and its metabolites were assessed using microdialysis. Our data suggest that subthalamic high-frequency stimulation increases striatal DA release and activates independent striatal DA metabolism. Since such changes could be triggered by modification of either the activity or the gene expression of the rate-limiting enzyme tyrosine hydroxylase, an activity assay and RT-PCR of striatal and nigral samples were performed. Subthalamic stimulation increased striatal tyrosine hydroxylase activity without affecting gene expression. We, therefore, conclude that the application of subthalamic high-frequency stimulation could partially compensate for the DA deficit by inducing increased striatal DA release and metabolism.

Animals↗

PubMed2003

The deafferented nonhuman primate is not a reliable model of intractable pain.

Before extending the application of motor cortex stimulation it is important to investigate the intimate mechanisms by which it alleviates intractable pain and to consider possible side effects. Self-mutilation in animals following extensive neurectomy or posterior rhizotomy of a limb is thought to reveal severe dysesthesias in the deafferented zone suggesting its usefulness as an animal model of chronic pain in humans. We here show in deafferented nonhuman primates that the autotomy behavior immediately follows the surgery and disappears after 28 days. In keeping with the experience of Y. Lamarre, the simple but careful care of all wounds is sufficient to abolish this behavior. Our results do not exclude the possibility that the deafferentiation is still painful for the monkeys, but they definitely rule out that autotomy is a consistent response to deafferentation.

Animals↗

PubMed2003

Time-course of nigrostriatal degeneration in a progressive MPTP-lesioned macaque model of Parkinson's disease.

Parkinson's disease (PD) is characterized by a progressive loss of substantia nigra pars compacta (SNc) neurons. The onset of clinical symptoms only occurs after the degeneration has exceeded a certain threshold. In most of the current 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) nonhuman primate models, nigrostriatal lesions and the onset of PD symptoms are the result of an immediate neuronal degeneration in the SNc caused by acute injection of the toxin. In order to develop a model that more closely mimics the degeneration pattern of human PD, we eventually established a protocol that produces a progressive parkinsonian state by treating monkeys repeatedly with MPTP for 15 +/- 2 d. Mean onset of parkinsonian symptoms occurred after 13.2 d of treatment. At this time, 56.8 +/- 6.3% of tyrosine hydroxylase immunoreactive neurons and 75.2 +/- 6.2% of Nissl-stained cells remained in the SNc. Striatal dopamine transporter (DAT) binding and dopamine (DA) content decreased to 19.7 +/- 4.9% and 18.2 +/- 5.6% of untreated monkeys. Parallel 123I-PEI single-photon emission computed tomography (SPECT) imaging in living animals showed a similar decrease in striatal DAT binding. In this article, we examine how this and other chronic MPTP models fit with human pathology.

Animals↗

PubMed2002

Deep brain stimulation of subthalamic neurons increases striatal dopamine metabolism and induces contralateral circling in freely moving 6-hydroxydopamine-lesioned rats.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) alleviates Parkinson's disease (PD) symptoms. Although widely used, the mechanisms of action are still unknown. In an attempt to elucidate those mechanisms, we have previously demonstrated that STN-DBS increases striatal extracellular dopamine (DA) metabolites in anaesthetized rats. PD being a movement disorder, it remains to be determined whether these findings are related to any relevant motor or behavioural changes. Thus, this study investigates concomitant behavioural changes during STN-DBS and extracellular striatal DA metabolites measured using microdialysis in freely moving 6-hydroxydopamine-lesioned rats. STN-DBS induced an increase of striatal DA metabolites in awake, freely moving animals. Furthermore, we observed concomitant contralateral circling behaviour. Taken together, these results suggest that STN-DBS could disinhibit (consequently activate) substantia nigra compacta neurons via inhibition of gamma-aminobutyric acid-ergic substantia nigra reticulata neurons.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2002

Oscillatory local field potentials recorded from the subthalamic nucleus of the alert rat.

Hitherto, high-frequency local field potential oscillations in the upper gamma frequency band (40-80 Hz) have been recorded only from the region of subthalamic nucleus (STN) in parkinsonian patients treated with levodopa. Here we show that local field potentials recorded from the STN in the healthy alert rat also have a spectral peak in the upper gamma band (mean 53 Hz, range 46-70 Hz). The power of this high-frequency oscillatory activity was increased by 30 +/- 4% (+/-SEM) during motor activity compared to periods of alert immobility. It was also increased by 86 +/- 36% by systemic injection of the D2 dopamine receptor agonist quinpirole. The similarities between the high-frequency activities in the STN of the healthy rat and in the levodopa-treated parkinsonian human argue that this oscillatory activity may be physiological in nature and not a consequence of the parkinsonian state.

Animals↗