Cyclosporin A ameliorates eclampsia seizure through reducing systemic inflammation in an eclampsia-like rat model.

Abstract

Our previous studies have shown that the maternal hyperinflammatory response in pre-eclampsia lowered the eclampsia-like seizure threshold. Cyclosporin A (CsA), which is an effective immunosuppressant, could attenuate the inflammatory responses in LPS-induced pre-eclampsia rats. Here, we hypothesized that CsA may ameliorate seizure severity through reducing systemic inflammation in pre-eclampsia/eclampsia. In the current study, the effects of CsA on pre-eclampsia manifestation, eclampsia-like seizure activities and systemic inflammation were examined in a pre-eclampsia model. Pregnant rats were given an intraperitoneal injection of the epileptogenic drug pentylenetetrazol (PTZ) following a tail vein injection of lipopolysaccharide to establish the eclampsia-like seizure model. CsA (5 mg/kg) was administered intravenously through the tail after LPS infusion. Mean systolic blood pressure and proteinuria in pre-eclampsia were detected. After PTZ injection, seizure activity was assessed, inflammatory responses were determined and pregnancy outcomes were analyzed. The results showed that CsA treatment significantly decreased blood pressure and proteinuria and increased the fetal and placental weight (P < 0.01). Meanwhile, CsA treatment significantly reduced serum IL-1β, TNF-α, and IL-17 levels (P < 0.01), decreased the seizure scores and prolonged the latency to seizure (P < 0.01). CsA effectively attenuated pre-eclampsia manifestation and eclampsia-like seizure severity. In addition, CsA treatment significantly reduced the inflammatory cytokine levels and improved pregnancy outcomes following eclampsia-like seizures. The decreased inflammatory cytokines in pre-eclampsia are coincident with attenuated pre-eclampsia manifestation after CsA treatment, suggesting that CsA treatment might decrease the eclampsia-like seizure severity through decreasing systemic inflammation in pre-eclasmpsia/eclampsia.