Methylene Blue Pretreatment Protects Against Repeated Neonatal Isoflurane Exposure-Induced Brain Injury and Memory Loss.

Perioperative neurocognitive impairment (PND) is a common medical complication in the postoperative period. General anesthesia through volatile anesthetics poses a high risk of POCD. Moreover, the developing brain is especially vulnerable to anesthesia-induced neurotoxicity. Therefore, finding a practical approach to prevent or alleviate neonatal isoflurane (ISO) exposure-induced brain injury and cognitive decline is essential for reducing medical complications following major surgery during the early postnatal period. Using a repeated neonatal ISO exposure-induced PND rat model, we investigated the effects of methylene blue (MB) pretreatment on repeated neonatal isoflurane exposure-induced brain injury and memory loss. Intraperitoneal injection of low-dose MB (1 mg/kg) was conducted three times 24 h before each ISO exposure. The Barnes maze and novel objection test were conducted to assess learning and memory. Immunofluorescence staining, F-Jade C staining, TUNEL staining, and Western blot analysis were performed to determine mitochondrial fragmentation, neuronal injury, degeneration, and apoptosis. Evans blue extravasation assay, total antioxidant capacity assay, MDA assay kit, and related inflammatory assay kits were used to test blood-brain barrier (BBB) disruption, antioxidant capacity, and neuroinflammation. Behavioral tests revealed that MB pretreatment significantly ameliorated ISO exposure-induced cognitive deficits. In addition, MB pretreatment alleviates neuronal injury, apoptosis, and degeneration. Furthermore, the BBB integrity was preserved by MB pretreatment. Additional studies revealed that ISO-induced excessive mitochondrial fragmentation, oxidative stress, and neuroinflammation were significantly attenuated by MB pretreatment in the PND rat model. Our findings suggest that MB pretreatment alleviates ISO exposure-induced brain injury and memory loss for the first time, supporting MB pretreatment as a promising approach to protect the brain against neonatal ISO exposure-induced postoperative cognitive dysfunction.

Molecular Hydrogen: an Emerging Therapeutic Medical Gas for Brain Disorders.

Oxidative stress and neuroinflammation are the main physiopathological changes involved in the initiation and progression of various neurodegenerative disorders or brain injuries. Since the landmark finding reported in 2007 found that hydrogen reduced the levels of peroxynitrite anions and hydroxyl free radicals in ischemic stroke, molecular hydrogen's antioxidative and anti-inflammatory effects have aroused widespread interest. Due to its excellent antioxidant and anti-inflammatory properties, hydrogen therapy via different routes of administration exhibits great therapeutic potential for a wide range of brain disorders, including Alzheimer's disease, neonatal hypoxic-ischemic encephalopathy, depression, anxiety, traumatic brain injury, ischemic stroke, Parkinson's disease, and multiple sclerosis. This paper reviews the routes for hydrogen administration, the effects of hydrogen on the previously mentioned brain disorders, and the primary mechanism underlying hydrogen's neuroprotection. Finally, we discuss hydrogen therapy's remaining issues and challenges in brain disorders. We conclude that understanding the exact molecular target, finding novel routes, and determining the optimal dosage for hydrogen administration is critical for future studies and applications.

MiR-214 Attenuates the Osteogenic Effects of Mechanical Loading on Osteoblasts.

Exercise is an effective way to prevent osteoporosis, but its mechanism remains unclear. MicroRNAs (miRNAs) play an essential role in bone metabolism. Recently, mechanical loading was reported to induce changes in miRNA expression in osteoblasts. However, the role of miRNAs in bone under exercise and its underlining mechanisms of action still remain unknown. MiR-214 was reported to regulate the process of osteogenesis and is considered a biomarker of osteoporosis. In this study, we aimed to investigate whether exercise could induce changes in miRNA expression in bone and to study the effects of miR-214 on mechanical loading-induced osteogenesis in osteoblasts. The results showed that miR-214 was down-regulated in both tibia from C57BL/6 mice after exercise in vivo and in osteoblasts after mechanical strain in vitro. Mechanical strain could enhance the ALP activity, promote matrix mineralization, up-regulate the expression of osteogenic factors such as ATF4, Osterix, ALP and ß-catenin, and down-regulate RANKL and RANK expression. Over-expression of miR-214 not only inhibited the expression of these osteogenic factors but also attenuated mechanical strain-enhanced osteogenesis in osteoblasts. Collectively, our results indicated that miR-214 could attenuate the osteogenic effects of mechanical loading on osteoblasts, suggesting that inhibition of miR-214 may be one of the ways in which exercise prevents osteoporosis.

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.

The effects of low-intensity He-Ne laser irradiation on erythrocyte metabolism.

Low-intensity laser irradiation (LILI) can improve the deformability of red blood cells (RBCs). It might be due to the LILI effects on adenosine triphosphate (ATP) level. However, ATP content may not be a valid surrogate marker for RBC deformability. The LILI effects on RBC glycolysis were studied in this paper. Hypertonic RBCs were used in this study. After 5 min irradiation with low-intensity He-Ne laser irradiation (LHNL) at 632.8 nm and 4.4 mW/cm(2), the concentration of intracellular glucose and the activities of phosphofructokinase (PFK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were measured, respectively. There was no significant change in intracellular glucose concentration. The activity of PFK decreased significantly, but the activity of GAPDH increased significantly. In hypertonic RBCs, LHNL irradiation may decrease the activity of energy-consuming enzymes, but increases the activity of energy-generating enzymes in glycolysis, to improve the RBC deformability.

Effects of low-level laser irradiation on rat skeletal muscle injury after eccentric exercise.

BACKGROUND AND OBJECTIVE: The effect of photobiomodulation on delayed onset muscle soreness remains unknown. This study represents the first investigation of this treatment using an animal model. METHODS: Seventy-two Sprague-Dawley rats were randomly divided into five groups: sedentary control group, exercise control group and three exercise-plus-laser groups. Downhill running was used to induce muscle injury in the gastrocnemius muscle. He-Ne laser irradiations were administered to the injured muscles immediately and at 18 and 42 h after exercise in the three exercise-plus-laser groups at 12, 28, and 43 J/cm2, respectively. Histological examination and serum creatine kinase (CK), muscle superoxide dismutase (SOD) and malondialdehyde (MDA) analyses were done at 24 and 48 h after exercise. RESULTS: The exercise control group exhibited a marked inflammation in the gastrocnemius muscle and significant elevations in serum CK activity and muscle MDA level after downhill running. He-Ne laser irradiation at 43 J/cm2 inhibited muscle inflammation, significantly enhanced muscle SOD activity and significantly reduced serum CK activity and muscle MDA level at both 24 and 48 h after exercise, whereas the irradiation at 12 or 28 J/cm2 slightly inhibited muscle inflammation and significantly reduced serum CK activity at 48 h after exercise only (P<0.05). CONCLUSIONS: Low-level He-Ne laser therapy could exert therapeutic effects on eccentric exercise-induced rat muscle injury through enhancing muscle anti-oxidative capacity and reducing the inflammatory reaction. The photobiomodulation was dose-dependent, and the 43 J/cm2 dose was the most efficient among the doses used.

Low-intensity laser irradiation improves the mitochondrial dysfunction of C2C12 induced by electrical stimulation.

OBJECTIVE: We investigated the effects of electrical stimulation and low-intensity laser (LIL) energy on the mitochondrial function of cultured C2C12 myotubes in order to find a dosage that could be used to improve the function of mitochondria, and then rehabilitate exercise-induced damage and fatigue. BACKGROUND DATA: Many other studies in the past demonstrated that LIL had a cytoprotective effect, and a recent study also found that LIL could reduce muscular fatigue during tetanic contractions in rats. METHODS: Cultured C2C12 myotubes were subjected to electrical stimulation or/and LIL irradiation at various intensities. Reactive oxygen species (ROS) were detected with a fluorescent probe (DCFH-DA) and mitochondrial function was assessed with an MTT assay. RESULTS: The results showed that electrical stimulation at 20 ms, 5 Hz, and 45 V for 75 min can induce mitochondrial dysfunction in cultured C2C12 myotubes. Electrical stimulation-induced mitochondrial dysfunction was improved, but degeneration occurred with LIL at doses of 0.33-8.22 and 11.22-14.16 J/cm2, respectively, and these changes were markedly increased with LIL at 0.33 and 1.34 J/cm2, respectively. CONCLUSIONS: We conclude that treatment of myotubes with the proper dosage of LIL irradiation significantly diminished production of ROS and restored mitochondrial function, and this may provide a foundation for the use of photobiomodulation to treat exercise-induced mitochondrial dysfunction or skeletal muscular fatigue.

Light emitting diode irradiation protect against the amyloid beta 25-35 induced apoptosis of PC12 cell in vitro.

BACKGROUND AND OBJECTIVES: Whether light emitting diode (LED) irradiation has effects on "beta-amyloid (A beta) induced apoptosis," a leading hypothesis of the cause of Alzheimer's disease (AD), or not? STUDY DESIGN/MATERIALS AND METHODS: Monolayer cell cultures of PC12 were subjected to A beta or/and LED irradiation at various intensity. Cell apoptosis was confirmed by morphological criteria, DNA fragmentation assay, and FAScan flow cytometer assay. RESULTS: Treatment of the cells with LED irradiation significantly diminished A beta induced apoptosis within 24 hours. CONCLUSIONS: The LED irradiation, when utilized at power of 0.9 W/m(2) and 60 minutes has significantly diminished A beta induced apoptosis of PC12 cells.