Research reportEffects of a higher dose of near-infrared light on clinical signs and neuroprotection in a monkey model of Parkinson's disease

•Near infrared light delivered intracranially at high dose is not toxic to brain.•Compared to lower NIr doses, higher doses are less beneficial after MPTP insult.•Clinical impairment after MPTP insult not improved greatly with higher NIr dose.•Neuroprotection after MPTP insult not substantial after higher NIr dose.

We have reported previously that intracranial application of near-infrared light (NIr) - when delivered at the lower doses of 25 J and 35 J - 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 (125 J) generated beneficial effects in the same MPTP monkey model (n=15). We implanted an NIr (670 nm) optical fibre device within a midline region of the midbrain in macaque monkeys, close to the substantia nigra of both sides. MPTP injections (1.8-2.1 mg/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 125 J was not as beneficial to MPTP-treated monkeys as compared to the lower doses of 25 J and 35 J, boding well for strategies of NIr dose delivery and device energy consumption in a future clinical trial.