Magnesium sulphate neuroprotection mechanism is placental mediated by inhibition of inflammation, apoptosis and oxidative stress

Abstract

IntroductionMaternal inflammation may induce placental cytokine production resulting in fetal exposure, and development of neonatal neurologic injury. Maternal magnesium sulphate (MG) is used as neuroprotective in preventing white matter brain injury. We sought to determine whether maternal MG can prevent placental activation of inflammatory pathways associated with fetal injury. MethodsPregnant Sprague Dawley rats at gestational day 20 (E20) (n = 24) received injections of intraperitoneal lipopolysaccharide (LPS; 500 μg/kg) or saline (SAL) at time 0. Dams were randomized to treatment with subcutaneous saline or MG for 2 h prior to and 2 h following LPS/saline injections. Four hours following first injection rats were sacrificed. Placentas were collected from all treatment groups (LPS/SAL, LPS/MG, SAL/MG, SAL/SAL). Placental Caspase 3, NF-kB p65, neuronal nitric oxide synthase (phospho-nNos) interleukin (IL)-6 and tumor necrotic factor-α (TNF-α) protein levels were determined by western blot and compared. ResultsMaternal LPS at E20 significantly increased protein levels of placental caspase 3 (0.22 ± 0.01 vs. 0.12 ± 0.01 u), NFkB p65 (0.27 ± 0.01 vs. 0.10 ± 0.01 u), phospho-nNOS (0.20 ± 0.01 vs. 0.10 ± 0.01 u) as well as IL-6 and TNF-α compared to control. MG treatment to LPS dams significantly reduced all placental mediators to levels similar to SAL/SAL controls (p < 0.05). DiscussionMaternal inflammation-induced fetal brain injury may be mediated via placental activation of inflammation, oxidative stress, and apoptotic pathways. The prevention of preterm brain injury could possibly intervene also via inhibition of one or more of these putative pathways.