Successive waves of CORT for 90 days greatly exacerbates LPS-induced neuroinflammation.

<p>Mice were treated with CORT (200 mg/L 0.6% EtOH) for 7 days in the drinking water followed either by 90 days without (CORT) or 90 days of bimonthly, 7 day CORT exposures (CORT+++). LPS (2 mg/kg, s.c.) was administered on day 97. TNFα, IL-1β, LIF, and OSM mRNA levels were measured in samples prepared from cortex collected 6 hours after LPS exposure. Data represent mean ± SEM (n = 5 mice/group). Statistical significance of at least P<0.05 is denoted by * as compared to appropriate control, # as compared to LPS alone, and § as compared to CORT/LPS.</p

Chronic CORT exacerbates PIC-induced neuroinflammation.

<p>Mice were pretreated with CORT (200 mg/L 0.6% EtOH in drinking water for one week). TNFα, IL-1β, LIF, and OSM mRNA levels were measured in samples prepared from cortex collected 6 hours after PIC exposure (12 mg/kg, i.p.). Data represent mean ± SEM (n = 5 mice/group). Statistical significance of at least P<0.05 is denoted by * as compared to respective control group.</p

Chronic CORT sensitizes the CNS to a sub-neuroinflammatory inhalation dose of LPS.

<p>Mice pretreated with CORT (200 mg/L 0.6% EtOH in drinking water for one week) were subjected to 3 hours of LPS (7.5 μg/m³) by inhalation. TNFα, IL-6, CCL2, IL-1β, LIF, and OSM mRNA levels were measured in samples prepared from cortex collected immediately following LPS inhalation exposure. Data represent mean ± SEM (n = 5 mice/group). Statistical significance of at least P<0.05 is denoted by * as compared to respective control and # as compared to LPS alone exposed group.</p

Chronic CORT exacerbates LPS-induced neuroinflammation brain wide.

<p>The effects of chronic CORT pretreatment (200 mg/L 0.6% EtOH in drinking water for one week) on LPS (2 mg/kg, s.c.)-induced TNFα, IL-6, CCL2, IL-1β, LIF, and OSM mRNA levels were measured in samples prepared from cortex (CTX), hippocampus (HIP), striatum (STR), hypothalamus (HYPO), olfactory bulb (OB), and cerebellum (CB) 6 hours after LPS exposure. Data represents mean ± SEM (n = 5 mice/group). Statistical significance of at least p<0.05 is denoted by * as compared to control, # as compared to LPS alone.</p

Chronic CORT pretreatment primes the neuroinflammatory response for 30 days.

<p>Mice were pretreated with CORT (200 mg/L 0.6% EtOH in drinking water for one week). Thirty days after the cessation of CORT, mice were administered LPS (2 mg/kg, s.c.). TNFα, IL-6, CCL2, IL-1β, LIF, and OSM mRNA levels were measured in samples prepared from cortex 6 hours after LPS exposure. Data represent mean ± SEM (n = 5 mice/group). Statistical significance of at least P<0.05 is denoted by * as compared to appropriate control and # as compared to LPS alone.</p

Chronic CORT pretreatment exacerbates and prolongs LPS-induced neuroinflammation but has no effect on activation of STAT3 and does not cause astrogliosis.

<p>A) A time course of LPS (2 mg/kg, s.c.)-induced neuroinflammation with and without CORT pretreatment (200 mg/L 0.6% EtOH in drinking water for one week) is shown (saline, 2, 6 and 12 hours). TNFα, IL-6, CCL2, IL-1β, LIF, and OSM mRNA levels were measured in samples prepared from cortex. Data represents mean ± SEM (n = 5 mice/group). CTX data for LPS alone treated groups are included from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0190546#pone.0190546.g001" target="_blank">Fig 1A</a> for statistical comparison. Statistical significance of at least p<0.05 is denoted by * as compared to control, # as compared to LPS alone, § as compared to 2h CORT/LPS, and ŧ as compared to 6h CORT/LPS. B & C) Effects of chronic CORT pretreatment (200 mg/L 0.6% EtOH in drinking water for one week) on LPS induced activation of the STAT3 signaling module was assessed by immunoblots of pSTAT3^Tyr705 and astrogliosis was assessed by immunoassay of GFAP. Cortex samples were analyzed for pSTAT3^Tyr705 (6 hours) and GFAP protein (72 hours) after LPS exposure of CORT pretreated animals. Data represent mean ± SEM (n = 5 mice/group). Saline and LPS alone treated groups are included from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0190546#pone.0190546.g001" target="_blank">Fig 1B & 1C</a> for statistical comparison. Statistical significance of at least p<0.05 is denoted by * as compared to control, # as compared to LPS alone.</p