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Neuroprotective Surgical Strategies in Parkinson's Disease: Role of Preclinical Data.

ABSTRACT: Although there have been many pharmacological agents considered to be neuroprotective therapy in Parkinson's disease (PD) patients, neurosurgical approaches aimed to neuroprotect or restore the degenerative nigrostriatal system have rarely been the focus of in depth reviews. Here, we explore the neuroprotective strategies involving invasive surgical approaches (NSI) using neurotoxic models 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA), which have led to clinical trials. We focus on several NSI approaches, namely deep brain stimulation of the subthalamic nucleus, glial neurotrophic derived factor (GDNF) administration and cell grafting methods. Although most of these interventions have produced positive results in preclinical animal models, either from behavioral or histological studies, they have generally failed to pass randomized clinical trials to validate each approach. We argue that NSI are promising approaches for neurorestoration in PD, but preclinical studies should be planned carefully in order not only to detect benefits but also to detect potential adverse effects. Further, clinical trials should be designed to be able to detect and disentangle neuroprotection from symptomatic effects. In summary, our review study evaluates the pertinence of preclinical models to study NSI for PD and how this affects their efficacy when translated into clinical trials.

SUBMITTER: Torres N

PROVIDER: S-EPMC5666871 | biostudies-other | 2017 Oct

REPOSITORIES: biostudies-other

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Neuroprotective Surgical Strategies in Parkinson's Disease: Role of Preclinical Data.

Torres Napoleon N Molet Jenny J Moro Cecile C Mitrofanis John J Benabid Alim Louis AL

International journal of molecular sciences 20171020 10

Although there have been many pharmacological agents considered to be neuroprotective therapy in Parkinson's disease (PD) patients, neurosurgical approaches aimed to neuroprotect or restore the degenerative nigrostriatal system have rarely been the focus of in depth reviews. Here, we explore the neuroprotective strategies involving invasive surgical approaches (NSI) using neurotoxic models 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA), which have led to clini ...[more]

PMID: 29053638

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Project description:Parkinson's disease (PD) is caused by progressive degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc), resulting in the deficiency of DA in the striatum. Thus, symptoms are developed, such as akinesia, rigidity and tremor. The aetiology of neuronal death in PD still remains unclear. Several possible mechanisms of the degeneration of dopaminergic neurons are still elusive. Various mechanisms of neuronal degeneration in PD have been proposed, including formation of free radicals, oxidative stress, mitochondrial dysfunction, excitotoxicity, calcium cytotoxicity, trophic factor deficiency, inflammatory processes, genetic factors, environmental factors, toxic action of nitric oxide, and apoptosis. All these factors interact with each other, inducing a vicious cycle of toxicity causing neuronal dysfunction, atrophy and finally cell death. Considerable evidence suggests that free radicals and oxidative stress may play key roles in the pathogenesis of PD. However, currently, drug therapy cannot completely cure the disease. DA replacement therapy with levodopa (L-Dopa), although still being a gold standard for symptomatic treatment of PD, only alleviates the clinical symptoms. Furthermore, patients usually experience severe side effects several years after the L-Dopa treatment. Until now, no therapy is available to stop or at least slow down the neurodegeneration in patients. Therefore, efforts are made not only to improve the effect of L-Dopa treatment for PD, but also to investigate new drugs with both antiparkinsonian and neuroprotective effects. Here, the advantages and limitations of current and future therapies for PD were dicussed. Current therapies include dopaminergic therapy, DA agonists, MAO-B inhibitor, COMT inhibitors, anticholinergic drugs, surgical procedures such as pallidotomy and more specifically deep brain stimulation of the globus pallidus pars interna (GPi) or subthalamic nucleus (STN), and stem cell transplantation.

Dataset Information

Neuroprotective Surgical Strategies in Parkinson's Disease: Role of Preclinical Data.

Publications

Neuroprotective Surgical Strategies in Parkinson's Disease: Role of Preclinical Data.

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