The effect of different doses of near infrared light on dopaminergic cell survival and gliosis in MPTP-treated mice

Abstract

We have used the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model to explore whether (i) the neuroprotective effect of near infrared light (NIr) treatment in the SNc is dose-dependent and (ii) the relationship between tyrosine hydroxylase (TH)+ terminal density and glial cells in the caudate-putamen complex (CPu). Mice received MPTP injections (50 mg/kg) and 2 J/cm2 NIr dose with either 2 d or 7 d survival period. In another series, with a longer 14 d survival period, mice had a stronger MPTP regime (100 mg/kg) and either 2 J/cm2 or 4 J/cm2 NIr dose. Brains were processed for routine immunohistochemistry and cell counts were made using stereology. Our findings were that in the 2 d series, no change in SNc TH+ cell number was evident after any treatment. In the 7 d series however, MPTP insult resulted in ∼45% reduction in TH+ cell number; after NIr (2 J/cm2) treatment, many cells were protected from the toxic insult. In the 14 d series, MPTP induced a similar reduction in TH+ cell number. NIr mitigated the loss of TH+ cells, but only at the higher dose of 4 J/cm2; the lower dose of 2 J/cm2 had no neuroprotective effect in this series. The higher dose of NIr, unlike the lower dose, also mitigated the MPTP- induced increase in CPu astrocytes after 14 d; these changes were independent of TH+ terminal density, of which, did not vary across the different experimental groups. In summary, we showed that neuroprotection by NIr irradiation in MPTP-treated mice was dose-dependent; with increasing MPTP toxicity, higher doses of NIr were required to protect cells and reduce astrogliosis.

Near‐infrared light is neuroprotective in a monkey model of Parkinson disease

“…Our experimental paradigm of simultaneous administration of MPTP insult and therapeutic application was similar to that of previous studies on animal models of PD . This paradigm is unlike clinical reality, where there is cell loss prior to therapeutic intervention.…”

“…Three monkeys had an optical fiber implant (but not activated) into the midbrain (see below), whereas 2 were left intact. A control group exposed to NIr was not included, because we have published previously that NIr has no impact on the survival and function of cells in normal brains . Given the consistency of these results, together with the rareness of primate tissue and the ethical considerations to reduce the number of primates used, we felt that the extra control group was redundant and not justified in our study. MPTP (n = 11): monkeys were administered 1.5mg/kg MPTP over 5 days (n = 6) or 2.1mg/kg over 7 days (n = 5); 10 of these monkeys were left intact, and 1 had an optical fiber implant (not activated). MPTP‐NIr (n = 9): monkeys were administered MPTP as above, in conjunction with optical fiber implants delivering NIr over 5 (total dose of 25J; n = 5) or 7 days (total dose of 35J; n = 4).…”

“…In essence, we explored whether there was true and/or functional neuroprotection. The number of nigral TH + and Nissl‐stained cells (main body of the nucleus, ie, ventral tier) was estimated using the optical fractionator method (Stereo Investigator; MBF Bioscience, Williston, VT), as outlined previously . Briefly, systematic random sampling of sites—with an unbiased counting frame—within defined boundaries of SNc was undertaken.…”

“…NIr treatment has been reported to reduce cell death, increase adenosine triphosphate (ATP) content, and decrease levels of oxidative stress among cultured cells after exposure to parkinsonian toxins . Furthermore, NIr offers neuroprotection to dopaminergic cells in the well‐known 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) mouse model and in the K369I transgenic mouse model, which also shows a progressive degeneration of nigral dopaminergic cells . Together with preserving dopaminergic cell survival in these models, NIr corrects the abnormal neuronal activity generated by MPTP toxicity, as well as improving locomotor activity …”

Low‐Intensity Photobiomodulation Decreases Neuropathic Pain in Paw Ischemia‐Reperfusion and Spared Nervus Ischiadicus Injury Experimental Models

“…Recent researches support the ability of light to penetrate the brain tissue and exert biological effects on photoacceptor molecules present in central nervous system structures . Several studies have shown its potential benefits in retinal diseases, stroke, neurodegeneration, neuromuscular disorders, and memory and mood disorders . In addition, the increase of the pain threshold in the right hindpaw of mice (measured by von Frey filaments) was demonstrated after photobiomodulation with infrared (810 nm) applied to different anatomical locations.…”