[53-OR]: Magnesium sulfate (MgSO4) increases seizure threshold via reduced neuroinflammation in a rat model of preeclampsia

Objectives The mechanism by which MgSO 4 provides seizure prophylaxis in women with preeclampsia (PE) remains unclear, and may be multifaceted. Here, we investigated the effect of MgSO 4 on seizure threshold, blood-brain barrier (BBB) permeability and neuroinflammation in a rat model of PE. Methods SD rats were pregnant ( P ; d20; n  = 19) or with PE (induced by combined placental ischemia and high cholesterol diet; n  = 14). A separate group of PE rats had MgSO 4 treatment via osmotic minipump to raise serum Mg 2+ to therapeutic levels for 24 h (PE + Mg; n  = 17). Seizure threshold was measured by i.v. infusion of pentylenetetrazol (PTZ) and simultaneous EEG, and the amount of PTZ (mg/kg) required to elicit seizure compared ( n  = 6/group). BBB permeability was measured in vivo by i.v. infusion of sodium fluorescein (NaFl) and fluorescent spectroscopy used to quantify passage into the brain ( n  = 5–7). Microglial activation, a measure of neuroinflammation, was compared between groups ( n  = 3–8) by immunostaining for ionized calcium binding adapter molecule 1 and assessed morphologically. Results Seizure threshold was lower in PE compared to P rats ( p 4 (Fig. 1). BBB permeability was increased in PE, with more NaFl passing into the brain compared to P rats (15.9 ± 1.0 vs. 12.2 ± 0.3 cts/g × 1000; p 4 (15.6 ± 1.0 cts/g × 1000; p  > 0.05). PE rats had neuroinflammation, characterized by activated microglia that was reversed by MgSO 4 (Fig. 1; p Conclusions PE was associated with lower seizure threshold, potentially due to increased BBB permeability and neuroinflammation. MgSO 4 increased seizure threshold in PE rats through a quiescent effect on microglia without affecting BBB permeability. Disclosures A.C. Johnson: None. M.J. Cipolla: None.