Photobiomodulation therapy promotes neurogenesis by improving post-stroke local microenvironment and stimulating neuroprogenitor cells.

Recent work has indicated that photobiomodulation (PBM) may beneficially alter the pathological status of several neurological disorders, although the mechanism currently remains unclear. The current study was designed to investigate the beneficial effect of PBM on behavioral deficits and neurogenesis in a photothrombotic (PT) model of ischemic stroke in rats. From day 1 to day 7 after the establishment of PT model, 2-minute daily PBM (CW, 808nm, 350mW/cm2, total 294J at scalp level) was applied on the infarct injury area (1.8mm anterior to the bregma and 2.5mm lateral from the midline). Rats received intraperitoneal injections of 5-bromodeoxyuridine (BrdU) twice daily (50mg/kg) from day 2 to 8 post-stoke, and samples were collected at day 14. We demonstrated that PBM significantly attenuated behavioral deficits and infarct volume induced by PT stroke. Further investigation displayed that PBM remarkably enhanced neurogenesis and synaptogenesis, as evidenced by immunostaining of BrdU, Ki67, DCX, MAP2, spinophilin, and synaptophysin. Mechanistic studies suggested beneficial effects of PBM were accompanied by robust suppression of reactive gliosis and the production of pro-inflammatory cytokines. On the contrary, the release of anti-inflammatory cytokines, cytochrome c oxidase activity and ATP production in peri-infarct regions were elevated following PBM treatment. Intriguingly, PBM could effectively switch an M1 microglial phenotype to an anti-inflammatory M2 phenotype. Our novel findings indicated that PBM is capable of promoting neurogenesis after ischemic stroke. The underlying mechanisms may rely on: 1) promotion of proliferation and differentiation of internal neuroprogenitor cells in the peri-infarct zone; 2) improvement of the neuronal microenvironment by altering inflammatory status and promoting mitochondrial function. These findings provide strong support for the promising therapeutic effect of PBM on neuronal repair following ischemic stroke.

Low-Level Laser Irradiation Improves Depression-Like Behaviors in Mice.

Major depressive disorder (MDD) is one of the leading forms of psychiatric disorders, characterized by aversion to mobility, neurotransmitter deficiency, and energy metabolic decline. Low-level laser therapy (LLLT) has been investigated in a variety of neurodegenerative disorders associated with mitochondrial dysfunction and functional impairments. The goal of this study was to examine the effect of LLLT on depression-like behaviors and to explore the potential mechanism by detecting mitochondrial function following LLLT. Depression models in space restriction mice and Abelson helper integration site-1 (Ahi1) knockout (KO) mice were employed in this work. Our results revealed that LLLT effectively improved depression-like behaviors, in the two depression mice models, by decreasing immobility duration in behavioral despair tests. In addition, ATP biosynthesis and the level of mitochondrial complex IV expression and activity were significantly elevated in prefrontal cortex (PFC) following LLLT. Intriguingly, LLLT has no effects on ATP content and mitochondrial complex I-IV levels in other tested brain regions, hippocampus and hypothalamus. As a whole, these findings shed light on a novel strategy of transcranial LLLT on depression improvement by ameliorating neurotransmitter abnormalities and promoting mitochondrial function in PFC. The present work provides concrete groundwork for further investigation of LLLT for depression treatment.

Low-level laser therapy for beta amyloid toxicity in rat hippocampus.

Beta amyloid (Aß) is well accepted to play a central role in the pathogenesis of Alzheimer's disease (AD). The present work evaluated the therapeutic effects of low-level laser irradiation (LLI) on Aß-induced neurotoxicity in rat hippocampus. Aß 1-42 was injected bilaterally to the hippocampus CA1 region of adult male rats, and 2-minute daily LLI treatment was applied transcranially after Aß injection for 5 consecutive days. LLI treatment suppressed Aß-induced hippocampal neurodegeneration and long-term spatial and recognition memory impairments. Molecular studies revealed that LLI treatment: (1) restored mitochondrial dynamics, by altering fission and fusion protein levels thereby suppressing Aß-induced extensive fragmentation; (2) suppressed Aß-induced collapse of mitochondrial membrane potential; (3) reduced oxidized mitochondrial DNA and excessive mitophagy; (4) facilitated mitochondrial homeostasis via modulation of the Bcl-2-associated X protein/B-cell lymphoma 2 ratio and of mitochondrial antioxidant expression; (5) promoted cytochrome c oxidase activity and adenosine triphosphate synthesis; (6) suppressed Aß-induced glucose-6-phosphate dehydrogenase and nicotinamide adenine dinucleotide phosphate oxidase activity; (7) enhanced the total antioxidant capacity of hippocampal CA1 neurons, whereas reduced the oxidative damage; and (8) suppressed Aß-induced reactive gliosis, inflammation, and tau hyperphosphorylation. Although development of AD treatments has focused on reducing cerebral Aß levels, by the time the clinical diagnosis of AD or mild cognitive impairment is made, the brain is likely to have already been exposed to years of elevated Aß levels with dire consequences for multiple cellular pathways. By alleviating a broad spectrum of Aß-induced pathology that includes mitochondrial dysfunction, oxidative stress, neuroinflammation, neuronal apoptosis, and tau pathology, LLI could represent a new promising therapeutic strategy for AD.