ABSTRACT
Propose/aim of study: Modafinil (MD) is a psychostimulant drug used off-label and cognitive dysfunction may be a significant emerging treatment target for this drug. The objective of this study was to evaluate the effect of MD on the neurochemical parameters and memory impairment of rats submitted to sepsis by cecal ligation and perforation (CLP).Material and method: Male Wistar rats (250-350g) were submitted to CLP, or sham as control, and divided into the sham + water, sham + MD (300 mg/kg), CLP + water, and CLP + MD (300 mg/kg) groups. Ten days after the administration of MD and CLP, the rats were submitted to a memory test by passive avoidance apparatus being sacrificed. The nitrite and nitrate (N/N) concentration, myeloperoxidase (MPO) and catalase (CAT) activity, lipid and protein oxidative damage, and brain-derived neurotrophic factor (BDNF) levels were measured in the prefrontal cortex and hippocampus.Results: The passive avoidance test verified an increase in the latency time compared training and test section in the groups sham + water and CLP + MD. Decreased N/N concentration and MPO activity were verified in the prefrontal cortex of rats submitted to CLP and MD treatment, as well as reduced protein and lipid oxidative damage in the hippocampus, which was accompanied by increased CAT activity and BDNF levels.Conclusion: Our data indicate the role of MD in attenuating oxidative stress parameters, the alteration of BDNF, and an improvement in memory impairment in rats ten days after induction of sepsis.
ABSTRACT
This study evaluated the effects of continuous and interval running on a treadmill on mechanical hyperalgesia in an animal model of chronic postischemia pain and analyzed the mechanism of action of this effect. Different groups of male Swiss mice with chronic postischemia pain, induced by 3 hours of paw ischemia followed by reperfusion, ran on the treadmill in different protocols-the speed (10, 13, 16, or 19 m/min), duration (15, 30, or 60 minutes), weekly frequency (3 or 5 times), weekly increase in continuous and interval running speed-were tested. Mechanical hyperalgesia was evaluated by von Frey filament 7, 14, and 21 days after paw ischemia followed by reperfusion. On day 11 after paw ischemia followed by reperfusion and after 5 days of continuous and interval running, concentrations of cytokines, oxidative stress parameters, and extracellular signal-regulated kinase 1/2 and AKT 1/2/3 expression in the spinal cord were measured. The results showed that continuous running has an antihyperalgesic effect that depends on intensity and volume. Interval running has a longer-lasting antihyperalgesic effect than continuous running. The antihyperalgesic effect depends on intensity and volume in continuous running, and increasing speed maintains the antihyperalgesic effect in both protocols. In the spinal cord, both runs decreased tumor necrosis factor-α and interleukin-6 levels and increased interleukin-10. Both running protocols reduced oxidative damage in the spinal cord. Only interval running had lower concentrations of phosphorylated extracellular signal-regulated kinase 1/2 in the spinal cord. Interval running presented a great antihyperalgesic potential with more promising results than continuous running, which may be owing to the fact that the interval running can activate different mechanisms from those activated by continuous running. PERSPECTIVE: A minimum of .5-hour sessions of moderate to high intensity ≥3 times a week are essential parameters for continuous and interval running-induced analgesia. However, interval running was shown to be more effective than continuous running and can be an important adjuvant treatment to chronic pain.
