title: Effects of a higher dose of near-infrared light on clinical signs and neuroprotection in a monkey model of Parkinson's disease.
abstract: We have reported previously that intracranial application of near-infrared light (NIr) - when delivered at the lower doses of 25J and 35J - reduces clinical signs and offers neuroprotection in a subacute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of Parkinson's disease. In this study, we explored whether a higher NIr dose (125J) generated beneficial effects in the same MPTP monkey model (n=15). We implanted an NIr (670nm) optical fibre device within a midline region of the midbrain in macaque monkeys, close to the substantia nigra of both sides. MPTP injections (1.8-2.1mg/kg) were made over a five day period, during which time the NIr device was turned on and left on continuously throughout the ensuing three week survival period. Monkeys were evaluated clinically and their brains processed for immunohistochemistry and stereology. Our results showed that the higher NIr dose did not have any toxic impact on cells at the midbrain implant site. Further, this NIr dose resulted in a higher number of nigral tyrosine hydroxylase immunoreactive cells when compared to the MPTP group. However, the higher NIr dose monkeys showed little evidence for an increase in mean clinical score, number of nigral Nissl-stained cells and density of striatal tyrosine hydroxylase terminations. In summary, the higher NIr dose of 125J was not as beneficial to MPTP-treated monkeys as compared to the lower doses of 25J and 35J, boding well for strategies of NIr dose delivery and device energy consumption in a future clinical trial.
authors.affiliation: CLINATEC, EJ Safra Centre, CEA, LETI, University of Grenoble, Alpes F38000, France. Electronic address: cecile.moro@cea.fr.
authors.forename: Cécile
authors.initials: C
authors.lastname: Moro
authors.affiliation: Dept of Anatomy F13, University of Sydney, 2006, Australia. Electronic address: nabil.elmassri@sydney.edu.au.
authors.forename: Nabil
authors.initials: N
authors.lastname: El Massri
authors.affiliation: CLINATEC, EJ Safra Centre, CEA, LETI, University of Grenoble, Alpes F38000, France. Electronic address: fannie.darlot@cea.fr.
authors.forename: Fannie
authors.initials: F
authors.lastname: Darlot
authors.affiliation: CLINATEC, EJ Safra Centre, CEA, LETI, University of Grenoble, Alpes F38000, France. Electronic address: napoleon.torres@cea.fr.
authors.forename: Napoleon
authors.initials: N
authors.lastname: Torres
authors.affiliation: CLINATEC, EJ Safra Centre, CEA, LETI, University of Grenoble, Alpes F38000, France. Electronic address: cl.chabrol@cea.fr.
authors.forename: Claude
authors.initials: C
authors.lastname: Chabrol
authors.affiliation: CLINATEC, EJ Safra Centre, CEA, LETI, University of Grenoble, Alpes F38000, France. Electronic address: diane.agay@cea.fr.
authors.forename: Diane
authors.initials: D
authors.lastname: Agay
authors.affiliation: CLINATEC, EJ Safra Centre, CEA, LETI, University of Grenoble, Alpes F38000, France. Electronic address: vincent.auboiroux@cea.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Auboiroux
authors.affiliation: Dept of Physiology F13, University of Sydney, 2006, Australia. Electronic address: daniel.johnstone@sydney.edu.au.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Johnstone
authors.affiliation: Dept of Physiology F13, University of Sydney, 2006, Australia. Electronic address: jonathan.stone@sydney.edu.au.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Stone
authors.affiliation: Dept of Anatomy F13, University of Sydney, 2006, Australia. Electronic address: john.mitrofanis@sydney.edu.au.
authors.forename: John
authors.initials: J
authors.lastname: Mitrofanis
authors.affiliation: CLINATEC, EJ Safra Centre, CEA, LETI, University of Grenoble, Alpes F38000, France. Electronic address: alimlouis@sfr.fr.
authors.forename: Alim-Louis
authors.initials: AL
authors.lastname: Benabid
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects; D004307:Dose-Response Relationship, Radiation; D000882:Haplorhini; D007259:Infrared Rays / Q000627:therapeutic use*; D028022:Low-Level Light Therapy; D020267:MPTP Poisoning; D008251:Macaca; D008636:Mesencephalon / Q000187:drug effects; D017072:Neostriatum / Q000378:metabolism; D000066829:Neuroprotection / Q000502:physiology; D010300:Parkinson Disease / Q000517:prevention & control / Q000628:therapy*; D020734:Parkinsonian Disorders; D010789:Phototherapy / Q000379:methods*; D013378:Substantia Nigra / Q000187:drug effects
chemical_list: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine
keywords: 670nm; Behaviour; MPTP; Macaque monkeys; Substantia nigra; Tyrosine hydroxylase