Beta amyloid (Aβ) 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 Aβ-induced neurotoxicity in rat hippocampus. Aβ 1–42 was injected bilaterally to the hippocampus CA1 region of adult male rats, and 2-minute daily LLI treatment was applied transcranially after Aβ injection for 5 consecutive days. LLI treatment suppressed Aβ-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 Aβ-induced extensive fragmentation; (2) suppressed Aβ-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 anti-oxidant expression; (5) promoted cytochrome c oxidase activity and adenosine triphosphate synthesis; (6) suppressed Aβ-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 Aβ-induced reactive gliosis, inflammation, and tau hyperphosphorylation. Although development of AD treatments has focused on reducing cerebral Aβ 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 Aβ levels with dire consequences for multiple cellular pathways. By alleviating a broad spectrum of Aβ-induced pathology that includes mitochondrial dysfunction, oxidative stress, neuroinflammation, neuronal apoptosis, and tau pathology, LLI could represent a new promising therapeutic strategy for AD.

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Transient global cerebral ischemia (GCI) causes delayed neuronal cell death in the vulnerable hippocampus CA1 subfield, as well as behavioral deficits. Ischemia reperfusion (I/R) produces excessive reactive oxygen species and plays a key role in brain injury. The mitochondrial electron respiratory chain is the main cellular source of free radical generation, and dysfunction of mitochondria has a significant impact on the neuronal cell death in ischemic brain. The aim of the present study is to investigate the potential beneficial effects of methylene blue (MB) in a 4-vessel occlusion (4VO) GCI model on adult male rats. MB was delivered at a dose of 0.5 mg/kg/day for 7 days, through a mini-pump implanted subcutaneously after GCI. We first found that MB significantly improved ischemic neuronal survival in hippocampal CA1 region as measured by cresyl violet staining as well as NeuN staining. We also found that MB has the ability to rescue ischemia-induced decreases of cytochrome c oxidase activity and ATP generation in CA1 region following I/R. Further analysis with labeling of MitoTracker® Red revealed that the depolarization of mitochondrial membrane potential (MMP) was markedly attenuated following MB treatment. In addition, the induction of caspase-3, -8 and -9 activities, and the increased numbers of TUNEL positive cells of CA1 region were significantly reduced by MB application. Correspondingly, Barnes maze tests showed that the deterioration of spatial learning and memory performance following GCI were significantly improved in MB-treatment group compared to ischemic control group. In summary, our study suggests that MB may be a promising therapeutic agent targeting neuronal cell death and cognitive deficits following transient global cerebral ischemia.

Promoting relaxation using virtual reality, olfactory interfaces and wearable EEG The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Amores, Judith et al. "Promoting relaxation using virtual reality, olfactory interfaces and wearable EEG.

Photobiomodulation (PBM) has been demonstrated as a neuroprotective strategy, but its effect on perinatal hypoxic-ischemic encephalopathy is still unknown. The current study was designed to shed light on the potential beneficial effect of PBM on neonatal brain injury induced by hypoxia ischemia (HI) in a rat model. Postnatal rats were subjected to hypoxic-ischemic insult, followed by a 7-day PBM treatment via a continuous wave diode laser with a wavelength of 808 nm. We demonstrated that PBM treatment significantly reduced HI-induced brain lesion in both the cortex and hippocampal CA1 subregions. Molecular studies indicated that PBM treatment profoundly restored mitochondrial dynamics by suppressing HI-induced mitochondrial fragmentation. Further investigation of mitochondrial function revealed that PBM treatment remarkably attenuated mitochondrial membrane collapse, accompanied with enhanced ATP synthesis in neonatal HI rats. In addition, PBM treatment led to robust inhibition of oxidative damage, manifested by significant reduction in the productions of 4-HNE, P-H2AX (S139), malondialdehyde (MDA), as well as protein carbonyls. Finally, PBM treatment suppressed the activation of mitochondria-dependent neuronal apoptosis in HI rats, as evidenced by decreased pro-apoptotic cascade 3/9 and TUNEL-positive neurons. Taken together, our findings demonstrated that PBM treatment contributed to a robust neuroprotection via the attenuation of mitochondrial dysfunction, oxidative stress, and final neuronal apoptosis in the neonatal HI brain.