Repeated transcranial low‐level laser therapy for traumatic brain injury in mice: biphasic dose response and long‐term treatment outcome

Abstract

We previously showed that near-infrared laser photobiomodulation (PBM) (810 nm, CW, 18 J/cm2, 25 mW/cm2) delivered to the mouse daily for 3-days after a controlled cortical impact traumatic brain injury (TBI) gave a significant improvement in neurological/cognitive function. However the same parameters delivered 14X daily gave significantly less benefit. This biphasic dose response intrigued us, and we decided to follow the mice that received 3X or 14X laser treatments out to 56-days post-TBI. We found the 14X group showed worse neurological function than the no-treatment TBI group at 2-weeks, but started to improve steadily during the next 6-weeks, and by 56-days were significantly better than the no-treatment TBI mice, but still worse than the 3X mice. A marker of activated glial cells (GFAP) was significantly increased in the brain regions (compared to both untreated TBI and 3X groups) at 4-weeks in the 14X group, but the GFAP had fallen to low levels in both 3X and 14X groups by 8-weeks. We conclude that an excessive number of laser-treatments delivered to mice can temporarily inhibit the process of brain repair stimulated by tPBM, but then the inhibitory effect ceases, and brain repair can resume. The mechanism may be temporary induction of reactive gliosis.

Mitochondrial Dysfunction and Parkinson’s Disease—Near-Infrared Photobiomodulation as a Potential Therapeutic Strategy

“…Intriguingly, the beneficial effects of NIR PBM follow a biphasic dose-response curve which adheres closely to the Arndt-Schulz principle (Huang et al, 2009;Sharma et al, 2011;Xuan et al, 2016). At very low doses of stimulation, the effects of PBM are negligible.…”

Effects of altitude changes on mild‑to‑moderate closed‑head injury in rats following acute high‑altitude exposure

“…Additionally, GFAP levels increase when cerebral tissues are damaged due to trauma (52). GFAP is an early diagnostic indicator of TBI and a sensitive indicator of mortality following TBI (53). GFAP is further the major protein of glial intermediate filaments in astrocytes and is often used as a hallmark of astrocyte reactivity (54).…”

Transcranial Low-Level Laser Therapy for Depression and Alzheimer’s Disease

“…Recently, researchers have shifted the focus of research to the application of LLLT on brain disorders [1][2][3]. During the past decade, LLLT has been widely used to study neurological and psychological diseases [3] such as depressionlike behaviors [4][5][6][7][8], Alzheimer's disease (AD) [9][10][11][12][13][14][15][16][17][18][19][20], Parkinson's disease [21], stroke [22,23] and traumatic brain injury (TBI) [24][25][26][27][28][29][30][31][32]. Because red or NIR light can effectively penetrate into brain tissues [33,34], it can be noninvasive and play a beneficial role in increasing ATP biosynthesis and neurogenesis [1,2].…”

“…Transcranial LLLT improved neuromuscular performance, increased brain derived neurotrophic factor (BDNF), reduced brain lesion volume, enhanced learning and memory, and overall improved the neurological severity score in mouse model of TBI [24,25,[28][29][30][31][32]. In addition, the clinical studies found that LLLT could improve cognition and decrease depression, anxiety, headache and insomnia in patients with chronic Review Xiang-Ping Chu and long-term spatial and recognition memory impairments in rats that were injected bilaterally with Aβ 1-42 to the hippocampus CA1 region [9].…”