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Dasatinib and quercetin (D & Q) have demonstrated promise in improving aged-related pathophysiological dysfunctions in humans and mice. Herein we aimed to ascertain whether the heat stress (HS)-induced cognitive deficits in aged or even young adult male mice can be reduced by D & Q therapy. Before the onset of HS, animals were pre-treated with D & Q or placebo for 3 consecutive days every 2 weeks over a 10-week period. Cognitive function, intestinal barrier permeability, and blood-brain barrier permeability were assessed. Compared to the non-HS young adult male mice, the HS young adult male mice or the aged male mice had significantly lesser extents of the exacerbated stress reactions, intestinal barrier disruption, endotoxemia, systemic inflammation and oxidative stress, blood-brain barrier disruption, hippocampal inflammation and oxidative stress, and cognitive deficits evaluated at 7 days post-HS. All the cognitive deficits and other syndromes that occurred in young adult HS mice or in aged HS mice were significantly attenuated by D & Q therapy (P < 0.01). Compared to the young adult HS mice, the aged HS mice had significantly (P < 0.01) higher severity of cognitive deficits and other related syndromes. First, our data show that aged male mice are more vulnerable to HS-induced cognitive deficits than those of the young adult male mice. Second, we demonstrate that a combination of D and Q therapy attenuates cognitive deficits in heat stressed aged or young adult male mice via broad normalization of the brain-gut-endotoxin axis function. [ABSTRACT FROM AUTHOR]

We first explore whether aircraft noise (AN) induces cognitive deficit via inducing oxidative damage in multiple vital organs including intestines, hearts and hippocampus tissues. Second, we explore whether the AN-induced cognitive deficits and inflammatory and oxidative damage to multiple organs can be alleviated by Astaxanthin (AX) pretreatment. Cognitive deficits were induced by subjecting the mice to AN 2 h daily for 7 consecutive days. An intragastrical dose of AX emulsifier (at the dose of daily feed intake [6 g] of a mouse three times weekly) was given to mice for consecutive 8 weeks prior to the start of AN. Cognitive functions were evaluated by using passive avoidance apparatus, Y-maze, Morris water maze and novel recognition test. Intestinal permeability was determined by measuring the intestinal clearance of fluorescein-isothiocyante. Evans Blue extravasation assay was used to measure the permeability of blood-brain-barrier. Inflammatory and oxidative damage to multiple organs were determined by measuring several pro-inflammatory cytokines and oxidative stress indicators in intestines; hearts and hippocampus. Mice treated with AN displayed exacerbated stress reactions, cognitive deficits, gut barrier hyperpermeability, increased upload of lipopolysaccharide translocation, systemic pro-inflammatory cytokines overproduction, blood-brain-barrier hyperpermeability, hippocampal neuroinflammation and increased levels of oxidative stress indicators in intestine, heart and hippocampus. All of the above-mentioned disorders caused by AN were significantly (P < 0.05) reversed by AX. Our data indicate that AX pretreatment alleviates cognitive deficits in aircraft noised mice by attenuating inflammatory and oxidative damage to intestines, hearts and hippocampal tissues. [ABSTRACT FROM AUTHOR]