Pulsed light irradiation improves behavioral outcome in a rat model of chronic mild stress
Background and objective:
Transcranial laser therapy (TLT) has been used successfully for the treatment of stroke in animal models and clinical trials. These results support the hypothesis that TLT could be used to treat other central nervous system conditions, such as depression. Current therapy for depression emphasizes pharmaco-therapeutics. However, these interventions often cause unwanted side effects. Here, TLT as a treatment for depression was studied in a rat model of chronic mild stress (CMS).
Study design/material and methods:
Wistar rats were randomized into four experimental groups (n = 8): (1) No-stress; (2) stress without treatment (Stress); (3) stress treated with an antidepressant (Drug); and (4) stress treated with TLT (TLT). The rats in the stress groups were exposed sequentially to a variety of mild stressors for 8 weeks. Rats were weighed weekly. After 5 weeks of stressing, the Drug group received a daily injection of fluoxetine (10 mg/kg), and the TLT group was irradiated transcranially 3 times a week (810 nm wavelength laser, 3 mm diameter probe, 350 mW peak power, 100 Hz with 20% duty cycle, 2-minute treatment time, 120 J/cm(2) average energy density on skin surface). After 3 weeks of treatment, a forced swimming test (FST) was performed and recorded for behavioral assessment. Animals were euthanized after 8 weeks of the study.
The No-stress group had significantly higher body weight than stress groups from week 5 (P < 0.05). No weight difference was found between the stress groups before treatment. However, the Drug group had significantly less body weight than both Stress and TLT groups after 2 weeks of treatment (P < 0.05). FST showed that the Stress group had significantly more immobility than the No-stress group (P < 0.05). Both Drug and TLT groups had significantly less immobility than the stress group (P < 0.05). There was no significant difference in immobility between both Drug and TLT groups (P = 0.62).
TLT was comparable to fluoxetine in improving the behavioral outcome after CMS. TLT did not cause weight loss, which is consistently seen in patients treated with fluoxetine. This study demonstrates that TLT has potential as an effective treatment for depression.
Psychological benefits 2 and 4 weeks after a single treatment with near infrared light to the forehead: a pilot study of 10 patients with major depression and anxiety
Many studies have reported beneficial effects from the application of near-infrared (NIR) light photobiomodulation (PBM) to the body, and one group has reported beneficial effects applying it to the brain in stroke patients. We have reported that the measurement of a patient’s left and right hemispheric emotional valence (HEV) may clarify data and guide lateralized treatments. We sought to test whether a NIR treatment could 1. improve the psychological status of patients, 2. show a relationship between immediate psychological improvements when HEV was taken into account, and 3. show an increase in frontal pole regional cerebral blood flow (rCBF), and 4. be applied without side effects.
We gave 10 patients, (5 M/5 F) with major depression, including 9 with anxiety, 7 with a past history of substance abuse (6 with an opiate abuse and 1 with an alcohol abuse history), and 3 with post traumatic stress disorder, a baseline standard diagnostic interview, a Hamilton Depression Rating Scale (HAM-D), a Hamilton Anxiety Rating Scale (HAM-A), and a Positive and Negative Affect Scale (PANAS). We then gave four 4-minute treatments in a random order: NIR to left forehead at F3, to right forehead at F4, and placebo treatments (light off) at the same sites. Immediately following each treatment we repeated the PANAS, and at 2-weeks and at 4-weeks post treatment we repeated all 3 rating scales. During all treatments we recorded total hemoglobin (cHb), as a measure of rCBF with a commercial NIR spectroscopy device over the left and the right frontal poles of the brain.
At 2-weeks post treatment 6 of 10 patients had a remission (a score </= 10) on the HAM-D and 7 of 10 achieved this on the HAM-A. Patients experienced highly significant reductions in both HAM-D and HAM-A scores following treatment, with the greatest reductions occurring at 2 weeks. Mean rCBF across hemispheres increased from 0.011 units in the off condition to 0.043 units in the on condition, for a difference of 0.032 (95% CI: -0.016, 0.080) units, though this result did not reach statistical significance. Immediately after treatment the PANAS improved to a significantly greater extent with NIR “on” relative to NIR “off” when a hemisphere with more positive HEV was treated than when one with more negative HEV was treated. We observed no side effects.
This small feasibility study suggests that NIR-PBM may have utility for the treatment of depression and other psychiatric disorders and that double blind randomized placebo-controlled trials are indicated.
Transcranial near-infrared photobiomodulation attenuates memory impairment and hippocampal oxidative stress in sleep-deprived mice
Sleep deprivation (SD) causes oxidative stress in the hippocampus and subsequent memory impairment. In this study, the effect of near-infrared (NIR) photobiomodulation (PBM) on learning and memory impairment induced by acute SD was investigated. The mice were subjected to an acute SD protocol for 72 h. Simultaneously, NIR PBM using a laser at 810 nm was delivered (once a day for 3 days) transcranially to the head to affect the entire brain of mice. The Barnes maze and the What-Where-Which task were used to assess spatial and episodic-like memories. The hippocampal levels of antioxidant enzymes and oxidative stress biomarkers were evaluated. The results showed that NIR PBM prevented cognitive impairment induced by SD. Moreover, NIR PBM therapy enhanced the antioxidant status and increased mitochondrial activity in the hippocampus of SD mice. Our findings revealed that hippocampus-related mitochondrial damage and extensive oxidative stress contribute to the occurrence of memory impairment. In contrast, NIR PBM reduced hippocampal oxidative damage, supporting the ability of 810 nm laser light to improve the antioxidant defense system and maintain mitochondrial survival. This confirms that non-invasive transcranial NIR PBM therapy ameliorates hippocampal dysfunction, which is reflected in enhanced memory function.
Antioxidant defense; Hippocampus; Memory; Mitochondria; Photobiomodulation; ROS.