title: Photobiomodulation inside the brain: a novel method of applying near-infrared light intracranially and its impact on dopaminergic cell survival in MPTP-treated mice.
abstract: OBJECTIVE
  Previous experimental studies have documented the neuroprotection of damaged or diseased cells after applying, from outside the brain, near-infrared light (NIr) to the brain by using external light-emitting diodes (LEDs) or laser devices. In the present study, the authors describe an effective and reliable surgical method of applying to the brain, from inside the brain, NIr to the brain. They developed a novel internal surgical device that delivers the NIr to brain regions very close to target damaged or diseased cells. They suggest that this device will be useful in applying NIr within the large human brain, particularly if the target cells have a very deep location.
  
  
  METHODS
  An optical fiber linked to an LED or laser device was surgically implanted into the lateral ventricle of BALB/c mice or Sprague-Dawley rats. The authors explored the feasibility of the internal device, measured the NIr signal through living tissue, looked for evidence of toxicity at doses higher than those required for neuroprotection, and confirmed the neuroprotective effect of NIr on dopaminergic cells in the substantia nigra pars compacta (SNc) in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson disease in mice.
  
  
  RESULTS
  The device was stable in freely moving animals, and the NIr filled the cranial cavity. Measurements showed that the NIr intensity declined as distance from the source increased across the brain (65% per mm) but was detectable up to 10 mm away. At neuroprotective (0.16 mW) and much higher (67 mW) intensities, the NIr caused no observable behavioral deficits, nor was there evidence of tissue necrosis at the fiber tip, where radiation was most intense. Finally, the intracranially delivered NIr protected SNc cells against MPTP insult; there were consistently more dopaminergic cells in MPTP-treated mice irradiated with NIr than in those that were not irradiated.
  
  
  CONCLUSIONS
  In summary, the authors showed that NIr can be applied intracranially, does not have toxic side effects, and is neuroprotective.
authors.affiliation: CEA-Leti, Grenoble, France; and.
authors.forename: Cécile
authors.initials: C
authors.lastname: Moro
authors.forename: Nabil El
authors.initials: NE
authors.lastname: Massri
authors.forename: Napoleon
authors.initials: N
authors.lastname: Torres
authors.forename: David
authors.initials: D
authors.lastname: Ratel
authors.forename: Xavier
authors.initials: X
authors.lastname: De Jaeger
authors.forename: Claude
authors.initials: C
authors.lastname: Chabrol
authors.forename: François
authors.initials: F
authors.lastname: Perraut
authors.forename: Alain
authors.initials: A
authors.lastname: Bourgerette
authors.forename: Michel
authors.initials: M
authors.lastname: Berger
authors.forename: Sivaraman
authors.initials: S
authors.lastname: Purushothuman
authors.forename: Daniel
authors.initials: D
authors.lastname: Johnstone
authors.forename: Jonathan
authors.initials: J
authors.lastname: Stone
authors.forename: John
authors.initials: J
authors.lastname: Mitrofanis
authors.forename: Alim-Louis
authors.initials: AL
authors.lastname: Benabid
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000528:radiation effects; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000166:cytology / Q000528:radiation effects*; D005240:Feasibility Studies; D007259:Infrared Rays; D008027:Light; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019635:Neurosurgical Procedures / Q000379:methods; D055100:Optical Fibers; D020734:Parkinsonian Disorders / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D010789:Phototherapy / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley