Magnesium sulphate neuroprotection mechanism is placental mediated by inhibition of inflammation, apoptosis and oxidative stress. (September 2022)

• Record Type: Journal Article
• Authors: Khatib, Nizar; Ginsberg, Yuval; Ben David, Chen; Ross, Michael G.; Vitner, Dana; Zipori, Yaniv; Zamora, Osnat; Weiner, Zeev; Beloosesky, Ron
• Is Part Of: Placenta. Volume 127(2022)
• Page Start: 29
• Page End: 36
• Publication Date: 2022-09
• Subjects: Inflammation -- Magnesium -- Neuroprotection -- Oxidative stress; magnesium sulphate MG -- lipopolysaccharide LPS -- neuronal nitric oxide synthase nNos -- interleukin IL -- tumor necrotic factor-α TNF-α -- NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells; Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2022.07.011
• Languages: English
• ISSNs: 0143-4004

Abstract

Abstract: Introduction: Maternal 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. Methods: Pregnant 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. Results: Maternal 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). Discussion: Maternal 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. Highlights: Administration of LPS increased levels of placental mediators of inflammation. Treatment with MG reduced placental mediators involved in inflammation. MG for prevention of preterm brain injury may work by inhibiting these pathways.