Poster Session I Thursday, January 26 • 10:30 AM - 12:00 PM • Octavius Ballroom| Volume 216, ISSUE 1, SUPPLEMENT , S120, January 01, 2017

183: Fetal neuroprotective effects of maternal magnesium for late gestation inflammation: inhibition of apoptosis, neuronal nitric oxide synthase and nf-kb activation


      In preterm birth, maternal magnesium sulphate (Mg) has been used as neuroprotective agent in preventing white matter brain injury. At term, chorioamnionitis and funisitis occur commonly and are associated with cerebral injury. Infection activates cell death pathways (apoptosis) and inflammatory responses through induction of caspase 3, oxidative stress and NF-kB pathways. We sought to determine if maternal Mg prevents the activation of apoptosis and inflammatory pathways in response to inflammation at late gestation.

      Study Design

      Pregnant rats at 20 days of gestation (24 total: 4 groups, n=6) received injections of i.p. lipopolysaccharide (LPS; 500 ug/kg) or saline (SAL) at time 0. Dams were randomized to treatment with s.c. saline or Mg (270 mg/kg loading followed by 27 mg/kg q20 min) for 2 hours prior to and 2 hours following LPS /saline injections. Rats were sacrificed 4 hours following LPS/ saline injection. Fetal brains were collected from the 4 treatment groups (LPS/SAL, LPS/Mg, SAL/MG, SAL/SAL). We used one fetal brain from each dam, resulting in 6 brains from 6 different dams in each group. Fetal brain caspase 3 active form (af), NF-kB p65, neuronal nitric oxide synthase (phospho-nNos) and protein levels of interleukin (IL)-6, IL-10 and TNFα were determined by western blot analysis.


      Maternal LPS (LPS/SAL) at e20 significantly (p<0.01) increased fetal brain caspase 3 af (0.27 ± 0.02 vs. 0.15 ± 0.06 u), NFkB p65 (0.23 ± 0.01 vs. 0.13 ± 0.01 u), and phospho-nNOS (0.22 ± 0.01 vs. 0.12 ± 0.01 u) as well as fetal brain pro-inflammatory cytokines (IL-6 0.21 ± 0.01 vs. 0.11 ± 0.01 u; TNFα 0.29 ± 0.01 vs. 0.15 ± 0.01 u) as compared to control fetuses (SAL/SAL). Maternal LPS did not alter fetal brain IL-10 levels. Mg treatment to LPS dams (LPS/Mg) significantly (p < 0.05) reduced fetal brain caspase 3 af (0.16 ± 0.01 u), NFkB p65 (0.11 ± 0.01 u) and phospho-Nnos (0.1 ± 0.01 u) as well as brain pro-inflammatory cytokines (IL-6 0.07 ± 0.01 u; TNFα 0.15 ± 0.01 u) to levels similar to Controls (SAL/SAL).


      Maternal and/or fetal inflammation-induced fetal brain injury may be mediated via activation of inflammation, oxidative stress and apoptosis pathways. Maternal Mg may prevent inflammation-induced brain injury at term via inhibition of these putative pathways.