title: Intracranial application of near-infrared light in a hemi-parkinsonian rat model: the impact on behavior and cell survival.
abstract: OBJECT The authors of this study used a newly developed intracranial optical fiber device to deliver near-infrared light (NIr) to the midbrain of 6-hydroxydopamine (6-OHDA)-lesioned rats, a model of Parkinson's disease. The authors explored whether NIr had any impact on apomorphine-induced turning behavior and whether it was neuroprotective. METHODS Two NIr powers (333 nW and 0.16 mW), modes of delivery (pulse and continuous), and total doses (634 mJ and 304 J) were tested, together with the feasibility of a midbrain implant site, one considered for later use in primates. Following a striatal 6-OHDA injection, the NIr optical fiber device was implanted surgically into the midline midbrain area of Wistar rats. Animals were tested for apomorphine-induced rotations, and then, 23 days later, their brains were aldehyde fixed for routine immunohistochemical analysis. RESULTS The results showed that there was no evidence of tissue toxicity by NIr in the midbrain. After 6-OHDA lesion, regardless of mode of delivery or total dose, NIr reduced apomorphine-induced rotations at the stronger, but not at the weaker, power. The authors found that neuroprotection, as assessed by tyrosine hydroxylase expression in midbrain dopaminergic cells, could account for some, but not all, of the observed behavioral improvements; the groups that were associated with fewer rotations did not all necessarily have a greater number of surviving cells. There may have been other "symptomatic" elements contributing to behavioral improvements in these rats. CONCLUSIONS In summary, when delivered at the appropriate power, delivery mode, and dosage, NIr treatment provided both improved behavior and neuroprotection in 6-OHDA-lesioned rats.
authors.affiliation: CEA, Leti, and Clinatec Departments, University Grenoble Alpes, Minatec Campus, Grenoble, France; and 
authors.forename: Florian
authors.initials: F
authors.lastname: Reinhart
authors.affiliation: Departments of 2 Anatomy and.
authors.forename: Nabil El
authors.initials: NE
authors.lastname: Massri
authors.affiliation: CEA, Leti, and Clinatec Departments, University Grenoble Alpes, Minatec Campus, Grenoble, France; and 
authors.forename: Claude
authors.initials: C
authors.lastname: Chabrol
authors.affiliation: CEA, Leti, and Clinatec Departments, University Grenoble Alpes, Minatec Campus, Grenoble, France; and 
authors.forename: Celine
authors.initials: C
authors.lastname: Cretallaz
authors.affiliation: Physiology, University of Sydney, New South Wales, Australia.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Johnstone
authors.affiliation: CEA, Leti, and Clinatec Departments, University Grenoble Alpes, Minatec Campus, Grenoble, France; and 
authors.forename: Napoleon
authors.initials: N
authors.lastname: Torres
authors.affiliation: CEA, Leti, and Clinatec Departments, University Grenoble Alpes, Minatec Campus, Grenoble, France; and 
authors.forename: Fannie
authors.initials: F
authors.lastname: Darlot
authors.affiliation: CEA, Leti, and Clinatec Departments, University Grenoble Alpes, Minatec Campus, Grenoble, France; and 
authors.forename: Thomas
authors.initials: T
authors.lastname: Costecalde
authors.affiliation: Physiology, University of Sydney, New South Wales, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Stone
authors.affiliation: Departments of 2 Anatomy and.
authors.forename: John
authors.initials: J
authors.lastname: Mitrofanis
authors.affiliation: CEA, Leti, and Clinatec Departments, University Grenoble Alpes, Minatec Campus, Grenoble, France; and 
authors.forename: Alim-Louis
authors.initials: AL
authors.lastname: Benabid
authors.affiliation: CEA, Leti, and Clinatec Departments, University Grenoble Alpes, Minatec Campus, Grenoble, France; and 
authors.forename: Cécile
authors.initials: C
authors.lastname: Moro
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002470:Cell Survival / Q000502:physiology / Q000528:radiation effects; D018491:Dopamine Agonists / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005240:Feasibility Studies; D007150:Immunohistochemistry; D028022:Low-Level Light Therapy; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology* / Q000528:radiation effects*; D009068:Movement / Q000187:drug effects / Q000528:radiation effects; D055100:Optical Fibers / Q000009:adverse effects; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D010789:Phototherapy / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D019736:Prostheses and Implants / Q000009:adverse effects; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine
keywords: 6-OHDA = 6-hydroxydopamine; 6-hydroxydopamine; ATP = adenosine-5’-triphosphate; CPu = caudate-putamen complex; GFAP = glial fibrillary acidic protein; IBA1 = ionized calcium binding adaptor molecule 1; LED = light-emitting diode; MPTP = 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NIr = near-infrared light; NIrC = continuous NIr at weaker power; NIrC+ = continuous NIr at stronger power; NIrP = pulse NIr; PBS = phosphate-buffered saline; Parkinson’s disease; RHS = right-hand side; SNc = substantia nigra pars compacta; SNr = substantia nigra pars reticulata; TH = tyrosine hydroxylase; VTA = ventral tegmental area; functional neurosurgery; neuroprotection; photobiomodulation; substantia nigra