ABSTRACT
Alzheimer's disease (AD) is a degenerative neurological disease that primarily affects the elderly. Drug therapy is the main strategy for AD treatment, but current treatments suffer from poor efficacy and a number of side effects. Non-drug therapy is attracting more attention and may be a better strategy for treatment of AD. Hypoxia is one of the important factors that contribute to the pathogenesis of AD. Multiple cellular processes synergistically promote hypoxia, including aging, hypertension, diabetes, hypoxia/obstructive sleep apnea, obesity, and traumatic brain injury. Increasing evidence has shown that hypoxia may affect multiple pathological aspects of AD, such as amyloid-beta metabolism, tau phosphorylation, autophagy, neuroinflammation, oxidative stress, endoplasmic reticulum stress, and mitochondrial and synaptic dysfunction. Treatments targeting hypoxia may delay or mitigate the progression of AD. Numerous studies have shown that oxygen therapy could improve the risk factors and clinical symptoms of AD. Increasing evidence also suggests that oxygen therapy may improve many pathological aspects of AD including amyloid-beta metabolism, tau phosphorylation, neuroinflammation, neuronal apoptosis, oxidative stress, neurotrophic factors, mitochondrial function, cerebral blood volume, and protein synthesis. In this review, we summarized the effects of oxygen therapy on AD pathogenesis and the mechanisms underlying these alterations. We expect that this review can benefit future clinical applications and therapy strategies on oxygen therapy for AD.
ABSTRACT
OBJECTIVE: To observe the expression of aquaporin-4 (AQP-4) mRNA and study the relationship between AQP-4, brain edema, pathological changes and ultrastructure of peri-hematoma tissue in intracerebral hemorrhage (ICH) patients. METHODS: Intracranial operation was performed via nonfunctional area with a funnel-like approach on 30 ICH patients. The brain tissue which must be removed 1 cm away the hematoma was removed within 12 hours for observation as normal brain tissue and taken as the control group (7 patients), and which of the brain tissue within 1 cm around hematoma was taken as the study specimens. The experimental group was subdivided into five groups according to the time interval after ICH: <6 hours (6 cases), 6-12 hours (7 cases), 12-24 hours (5 cases), 24-72 hours (6 cases), and >72 hours ( 6 cases ). Expression of the AQP-4 mRNA, brain edema, pathological and ultrastructural changes were observed with reverse transcription-polymerase chain reaction (RT-PCR), light microscope and electron microscope. RESULTS: The expression of the AQP-4 mRNA was not remarkable, the morphology and construction were basically normal in control group. The expression of AQP-4 mRNA was mild (1.17+/-0.41)and there was edema of neuroglia in the <6 hours group. After 6 hours, besides neuroglial edema, the expression of the AQP-4 mRNA was gradually obvious, capillary endothelial cells began to swell too, and tight junctions gradually began to loosen. In the 12-72 hours group the expression of the AQP-4 mRNA reached its peak (3.50+/-0.55, 3.60+/-0.55, both P<0.01), and brain edema was most prominent, and electron microscopy showed that neurons, neuroglia, and capillary endothelial cells were markedly deformed. After 72 hours, the expression of AQP-4 mRNA gradually recovered, and brain cells showed less damage. On the 5th day the damage began to repair, and on the 8th day, the damage was basically repaired. The correlation analysis showed that there was a remarkable positive correlation between the expression of the AQP-4 mRNA and the degree of brain edema and the size of hematoma (r(1)=0.67, P<0.01; r(2)=0.44, P<0.05) . CONCLUSION: Secondary edema and brain damage may correlate with the expression of the AQP-4 mRNA in the peri-hematoma brain edema area. Removal of hematoma will help decrease the AQP-4 mRNA expression and brain edema damage in the early stage.
