Intracranial application of near-infrared light in a hemi-parkinsonian rat model: the impact on behavior and cell survival

J Neurosurg. 2016 Jun;124(6):1829-41. doi: 10.3171/2015.5.JNS15735. Epub 2015 Nov 27.

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.

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.

MeSH terms

  • Animals
  • Apomorphine / pharmacology
  • Cell Survival / physiology
  • Cell Survival / radiation effects
  • Dopamine Agonists / pharmacology
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / pathology
  • Dopaminergic Neurons / physiology
  • Dopaminergic Neurons / radiation effects
  • Dose-Response Relationship, Radiation
  • Feasibility Studies
  • Immunohistochemistry
  • Low-Level Light Therapy
  • Male
  • Mesencephalon / drug effects
  • Mesencephalon / pathology
  • Mesencephalon / physiopathology*
  • Mesencephalon / radiation effects*
  • Movement / drug effects
  • Movement / radiation effects
  • Optical Fibers / adverse effects
  • Oxidopamine
  • Parkinsonian Disorders / pathology
  • Parkinsonian Disorders / physiopathology*
  • Parkinsonian Disorders / therapy*
  • Phototherapy / adverse effects
  • Phototherapy / instrumentation
  • Phototherapy / methods*
  • Prostheses and Implants / adverse effects
  • Rats, Wistar
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Dopamine Agonists
  • Oxidopamine
  • Tyrosine 3-Monooxygenase
  • Apomorphine