Document Detail

Exploring the neuroprotective effects of modafinil in a marmoset Parkinson model with immunohistochemistry, magnetic resonance imaging and spectroscopy.
MedLine Citation:
PMID:  18076869     Owner:  NLM     Status:  MEDLINE    
Neuroprotective therapeutics stop or slow down the degeneration process in animal models of Parkinson's disease (PD). Neuronal survival in PD animal models is often measured by immunohistochemistry. However, dynamic changes in the pathology of the brain cannot be explored with this technique. Application of proton magnetic resonance (MR) imaging (MRI) and spectroscopy (MRS) can cover this lacuna as these techniques are non-invasive and can be repeated over time in the same animal. Therefore, the sensitivity of both techniques to measure changes in PD-pathology was explored in an experiment studying the neuroprotective effects of the vigilance enhancer modafinil in a marmoset PD model. Eleven marmoset monkeys were treated with the neurotoxin 1-methyl-1,2,3,6-tetrahydropyridine (MPTP). Six of these 11 animals, simultaneously, received a daily oral dose of modafinil (100 mg/kg) and five received vehicle for 27 days. MR experiments were performed at baseline and 1 and 3.5 weeks after the MPTP intoxication period after which brains were analyzed with immunohistochemistry. Tyrosine hydroxylase immunoreactive (TH-IR) staining of dopamine neurons of the substantia nigra pars compacta confirmed that modafinil was able to partially prevent the MPTP-induced neuronal damage. In MRS, N-acetylaspartate (NAA)/phosphocreatine (tCR) ratios confirmed the protective effect indicating that this is a sensitive measure to detect neuroprotection in the MPTP marmoset model. Furthermore, the number of TH-IR positive neurons and the NAA/tCR ratio were significantly correlated to behavioral observations indicating that the changes measured in the brain are also reflected in the behavior and vice versa.
S A M van Vliet; S A M van Vlieta; E L A Blezer; M J Jongsma; R A P Vanwersch; B Olivier; I H C H M Philippens
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Publication Detail:
Type:  Journal Article     Date:  2007-11-01
Journal Detail:
Title:  Brain research     Volume:  1189     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-01-14     Completed Date:  2008-06-02     Revised Date:  2008-06-17    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  219-28     Citation Subset:  IM    
Department of Diagnosis and Therapy, TNO Defence, Security and Safety, Rijswijk, The Netherlands.
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MeSH Terms
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / adverse effects
Aspartic Acid / analogs & derivatives,  analysis,  metabolism
Benzhydryl Compounds / pharmacology*,  therapeutic use
Biological Markers
Brain / drug effects*,  metabolism,  pathology*
Disease Models, Animal
Dopamine / metabolism
Drug Administration Schedule
Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy
Nerve Degeneration / chemically induced,  drug therapy,  prevention & control
Neurons / drug effects,  metabolism,  pathology
Neuroprotective Agents / pharmacology*,  therapeutic use
Neurotoxins / adverse effects
Parkinsonian Disorders / drug therapy*,  metabolism,  pathology*
Phosphocreatine / analysis,  metabolism
Predictive Value of Tests
Reproducibility of Results
Substantia Nigra / drug effects,  metabolism,  pathology
Treatment Outcome
Tyrosine 3-Monooxygenase / metabolism
Reg. No./Substance:
0/Benzhydryl Compounds; 0/Biological Markers; 0/Neuroprotective Agents; 0/Neurotoxins; 28289-54-5/1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 56-84-8/Aspartic Acid; 67-07-2/Phosphocreatine; 68693-11-8/modafinil; 997-55-7/N-acetylaspartate; EC 3-Monooxygenase
Erratum In:
Brain Res. 2008 Apr 14;1204:123
Note: van Vlieta, S A M [corrected to van Vliet, S A M]

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