Combined exposure of heat stress and ozone enhanced cognitive impairment via neuroinflammation and blood brain barrier disruption in male rats

Heat stress (HS) exposure has been linked to cognitive dysfunction. In reality, high temperature does not occur alone in environment, and ozone (O3) and heatwaves usually co-exist in atmospheric environment. However, whether O3 exposure exacerbates HS-induced cognitive impairment and the potential underlying mechanisms have not been explored experimentally. The aim of this study was to determine the co-effects and mechanisms of HS and O3 on the cognitive dysfunction.48 Sprague Dawley male rats were randomly divided into 4 groups: control, HS, O3 and HS plus O3 (HO3) groups. Rats in HS and HO3 group were exposed to 40 °C every morning from 9:00 to 12:00 for 15 consecutive days. While rats in O3 and HO3 groups were exposed to 0.7 ppm O3 the same day from 14:00 to 17:00 for 15 days. Cognitive performance was examined with Morris water maze test. Neurodegeneration, glial activation, neuroinflammation, blood brain barrier (BBB) disruption and apoptosis were evaluated by Western blot, Elisa, immunohistochemistry and immunofluorescence staining.HS induced cognitive decline and neuronal damage in rats. Further studies showed that exposure of rats to HS could also induce glial activation, neuroinflammation and neuronal apoptosis in hippocampus, and decrease in the expressions of ZO-1, claudin-5 and occluding, indicative of BBB disruption. Impressively, the neuronal effects induced by HS, as depicted above, could be worsened by co-exposure to O3 in rats.Co-exposure to O3 promotes HS-induced cognitive impairment in rats possibly through glial-mediated neuroinflammation and BBB disruption.