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Magnesium modulates IL-6-induced maternal fever and increases fetal brain activated astrocytes
Abstract Number: BP-02
Abstract Type: Original Research
Background: Fever in labor is associated with seizures, cerebral palsy and other fetal brain injuries. Labor epidural analgesia is a common risk factor for intrapartum fever and is associated with a noninfectious increase in maternal interleukin-6 (IL-6)(1). We previously reported that systemic injection of IL-6 in pregnant rats leads to fever and fetal brain microglial activation and inflammation. Magnesium sulfate (MgSO4) is commonly used clinically and reduces the risk of neonatal brain injury(2). We hypothesized that maternal MgSO4 would alter the maternal and fetal brain effects of IL-6.
Methods: With DLAM approval, pregnant rats (N=9) were injected with either Saline (n=3), IL-6 (n=3) or MgSO4 and IL-6 (n=3) at 0, 1.5, and 3 hr on gestational day 20 (GD20; term=22d) and core temperature was recorded. 24 hr post injection, dams were anesthetized and fetal forebrains removed and processed for histochemical analyses of Glial Fibrillary Acidic Protein (GFAP), a marker of astrocyte activation. Temperature differences were compared by RM ANOVA and counts of GFAP+ cells were compared by chi-square.
Results: Compared to saline, IL-6 injection increased temperature while MgSO4 decreased it progressively at 3 hours (vehicle 37 ± 0.15 °C, IL-6 37.3 ± 0.14, IL-6 MgSO4 36.2 ± 0.4) (P=0.03). A rebound temperature increase was observed in the MgSO4 IL-6 group at 270 minutes (37 ± 0.5,P=0.03). The saline group showed very few GFAP- stained cells. IL-6 increased GFAP staining (50%) and IL-6 MgSO4 further increased GFAP+ cells (70%, p<0.05; Figure).
Conclusions: MgSO4 suppresses the IL-6-induced increase in maternal temperature, though the effect appears short-lived after discontinuation of the drug. MgSO4 also activates fetal astrocytes and tripotent stem cells in our model. GFAP is a marker of differentiated astrocytes, but it is also expressed in adult multipotent cells of the subventricular zone, an important area in developmental synaptogenesis(3-4). Astrocytes may also promote myelination, and protect neurons by several mechanisms. The possible neuroprotection of MgSO4 is a promising observation for future investigation.
1) AJOG 2002;187(4):834-838
2) NEJM 2008;359(9):895-905
3) Gen Dev 2012; 1;26(9):891-907
4) Acta Neurop. 2010;119(1):7-35