TY - JOUR
T1 - Fetal neuroprotective mechanism of maternal magnesium sulfate for late gestation inflammation
T2 - in a rodent model
AU - Khatib, Nizar
AU - Ginsberg, Yuval
AU - Shalom-Paz, Einat
AU - Dabaja, Hanin
AU - Gutzeit, Olga
AU - Zmora, Osnat
AU - Millo, Zvika
AU - Ross, Michael G.
AU - Weiner, Zeev
AU - Beloosesky, Ron
N1 - Publisher Copyright:
© 2019 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2020/11/16
Y1 - 2020/11/16
N2 - Background: Maternal administration of magnesium sulfate (Mg) is used in humans to protect the fetal brain during preterm delivery. We sought to determine the neuroprotective mechanism of Mg in a rat model of late gestation maternal inflammation. Methods: Pregnant rats at 20 d of gestation (20 total, four groups, N = 5 in each group) received i.p. LPS or saline. Dams were randomized for s.c. saline or Mg supplementation 2 h prior and following the LPS/saline injections. Dams were sacrificed 4 h following the last treatment. Fetal brains were collected from the four treatment groups. Fetal brain caspase 3 active form, NF-kB p65, neuronal nitric oxide synthase (phospho-nNos), and proinflammatory cytokines levels were determined by western blot. Results: Maternal LPS at e20 significantly (p <.01) increased fetal brain caspase 3 active form (af) (0.27 ± 0.02 versus 0.15 ± 0.06u), NFkB (0.23 ± 0.01 versus 0.13 ± 0.01u), and phospho-nNOS (0.22 ± 0.01 versus 0.12 ± 0.01u) and fetal brain proinflammatory cytokines (IL-6 0.21 ± 0.01 versus 0.11 ± 0.01 u; TNFα 0.29 ± 0.01 versus 0.15 ± 0.01u), compared with control fetuses. Mg treatment significantly (p <.05) reduced fetal brain caspase 3 af (0.16 ± 0.01u), NFkB p65 (0.11 ± 0.01u), phospho-nNOS (0.1 ± 0.01u), as well as brain proinflammatory cytokines (IL-6 0.07 ± 0.01u; TNFα 0.15 ± 0.01u) to levels similar to controls. Conclusion: Maternal inflammation-induced fetal brain injury at late gestation may be mediated by the activation of inflammatory response, oxidative stress, and apoptosis. Maternal Mg may attenuate the injury by inhibition of these putative pathways.
AB - Background: Maternal administration of magnesium sulfate (Mg) is used in humans to protect the fetal brain during preterm delivery. We sought to determine the neuroprotective mechanism of Mg in a rat model of late gestation maternal inflammation. Methods: Pregnant rats at 20 d of gestation (20 total, four groups, N = 5 in each group) received i.p. LPS or saline. Dams were randomized for s.c. saline or Mg supplementation 2 h prior and following the LPS/saline injections. Dams were sacrificed 4 h following the last treatment. Fetal brains were collected from the four treatment groups. Fetal brain caspase 3 active form, NF-kB p65, neuronal nitric oxide synthase (phospho-nNos), and proinflammatory cytokines levels were determined by western blot. Results: Maternal LPS at e20 significantly (p <.01) increased fetal brain caspase 3 active form (af) (0.27 ± 0.02 versus 0.15 ± 0.06u), NFkB (0.23 ± 0.01 versus 0.13 ± 0.01u), and phospho-nNOS (0.22 ± 0.01 versus 0.12 ± 0.01u) and fetal brain proinflammatory cytokines (IL-6 0.21 ± 0.01 versus 0.11 ± 0.01 u; TNFα 0.29 ± 0.01 versus 0.15 ± 0.01u), compared with control fetuses. Mg treatment significantly (p <.05) reduced fetal brain caspase 3 af (0.16 ± 0.01u), NFkB p65 (0.11 ± 0.01u), phospho-nNOS (0.1 ± 0.01u), as well as brain proinflammatory cytokines (IL-6 0.07 ± 0.01u; TNFα 0.15 ± 0.01u) to levels similar to controls. Conclusion: Maternal inflammation-induced fetal brain injury at late gestation may be mediated by the activation of inflammatory response, oxidative stress, and apoptosis. Maternal Mg may attenuate the injury by inhibition of these putative pathways.
KW - Inflammation
KW - magnesium sulfate
KW - neuroprotection; preterm delivery
UR - http://www.scopus.com/inward/record.url?scp=85062504055&partnerID=8YFLogxK
U2 - 10.1080/14767058.2019.1583735
DO - 10.1080/14767058.2019.1583735
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C2 - 30835601
AN - SCOPUS:85062504055
SN - 1476-7058
VL - 33
SP - 3732
EP - 3739
JO - Journal of Maternal-Fetal and Neonatal Medicine
JF - Journal of Maternal-Fetal and Neonatal Medicine
IS - 22
ER -