Effects of Low-Intensity Transcranial Pulsed Ultrasound Treatment in a Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease. One of the main pathology markers of AD is the beta-amyloid plaques (ßA1-42) created from residues of the badly processed amyloid precursor protein. The accumulation of these plaques can induce neuroinflammation and oxidative stress and impair antioxidant mechanisms, culminating in cognitive and memory deficits. New therapies are necessary to treat AD as the approved drugs do not treat the progress of the disease. Transcranial low-intensity pulsed ultrasound (LIPUS) affects brain metabolism and could be tested as a treatment for AD. This study was aimed at evaluating the LIPUS treatment in a model of AD induced by ßA1-42 intracerebroventricularly (ICV) and its effects on learning memory, neurotrophins, neuroinflammation and oxidative status. ßA1-42 was administered ICV 24 h before the start of a 5-wk LIPUS treatment. The treatment with LIPUS improved recognition memory, as well as increasing nerve growth factor ß and brain-derived neurotrophic factor levels in the hippocampus and cortex. There was a decrease in protein damage in the hippocampus treated with LIPUS. Neuroinflammation and oxidative stress were not present in the AD model used. The results indicated that LIPUS is a novel and promising adjuvant strategy for treatment of the late stage of AD.

Intranasal insulin treatment modulates the neurotropic, inflammatory, and oxidant mechanisms in the cortex and hippocampus in a low-grade inflammation model.

The inflammatory process plays a critical role in the development of neurodegenerative diseases. Insulin is used in preclinical and clinical studies of neurological disorders. Its intranasal (IN) administration directly in the brain allows for its peripheral metabolic effects to be avoided. Swiss male mice were injected with lipopolysaccharide (LPS) (0.1 mg/kg) to induce low-grade inflammation. IN insulin treatment was initiated 4 h later at a dose of 1.7 IU once daily for 5 days. LPS induced cognitive deficits, which the IN insulin treatment reversed. LPS significantly decreased, whereas IN insulin significantly increased the levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor-ß in the cortex. In the hippocampus, IN insulin significantly decreased the BDNF level. LPS significantly increased the interleukin (IL)-6 levels in the cortex, while IN Insulin significantly decreased its levels in the hippocampus. The tumor necrosis factor-α levels were significantly decreased by IN insulin both in the cortex and hippocampus. Moreover, IN insulin significantly increased the IL-10 levels in the cortex. The levels of oxidative and nitrosative stress were significantly higher in the LPS-treated mice; however, IN insulin had a modulatory effect on both. LPS significantly increased the antioxidant enzyme activity both in the cortex and hippocampus, whereas IN insulin significantly increased the activity of both superoxide dismutase and catalase in the hippocampus and that of catalase in the cortex. The hydrogen peroxide levels revealed that LPS significantly affected the electron transport chain. Therefore, IN insulin could be useful in the treatment of neuroinflammatory diseases.

Cardioprotective effects of physical exercise on redox biology in mice exposed to hand-rolled cornhusk cigarette smoke.

The present study sought to evaluate the effects of physical training on histological parameters and oxidative stress in the myocardium of mice chronically exposed to hand-rolled cornhusk cigarette (HRCC) smoke. Male Swiss mice (60 days old, 30-35 g) were either exposed to ambient air or passively exposed to the smoke of 12 cigarettes daily over 3 sessions (4 cigarettes per session) for 60 consecutive days with or without physical training for 8 weeks. Forty-eight hours after the last training session, the heart was surgically removed for histological analysis and measurement of oxidative stress parameters. Histological imaging revealed cell disruption, with poorly defined nuclei, in the mice exposed to HRCC smoke, but not in the control group. However, mice exposed to HRCC smoke with physical training displayed signs of tissue repair and improved tissue integrity. Biochemical analysis revealed decreased production of superoxide, 2',7'-dichlorofluorescein (DCF), and nitrite, as well as decreased protein carbonylation, in the physical training groups, likely due to the exercise-induced increase in glutathione peroxidase (GPX) activity and glutathione (GSH) content. Taken together, our results suggest that physical exercise exerts cardioprotective effects by modulating the redox responses in animals exposed to HRCC smoke.