Increased neuronal seizure activity correlates with excessive systemic inflammation in a rat model of severe preeclampsia

Abstract

Preeclampsia (PE), one of the most common disorders of pregnancy, is characterized by hypertension and albuminuria. In severe cases, PE results in eclampsia-like seizures. Studies have suggested that severe PE is related to an exaggerated systemic inflammatory response, which may increase sensitivity to seizures. In the current study, we investigated whether the seizure activity of neurons was enhanced under excessive systemic inflammation. We also sought to determine whether MgSO could reduce the effects of systemic inflammation on seizure activity after electrical stimulation in a lipopolysaccharide (LPS)-induced model of PE. In addition to pregnancy outcomes, we analyzed biochemical parameters to ascertain whether our PE model was successful. Enzyme-linked immunosorbent assay analysis revealed that the levels of inflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-1β) were significantly higher in the LPS-treated rats than in the untreated rats. After electrical stimulation, behavioral assessments showed that the LPS-treated rats that were not treated with MgSO had the shortest latency period to develop a seizure and the longest seizure duration. The electroencephalographic (EEG) recordings in the hippocampus demonstrated that this group also had the highest EEG amplitude. MgSO treatment significantly decreased both TNF-α and IL-1β concentrations, increased the latency to develop a seizure, decreased the seizure duration and shortened the EEG amplitude. These results suggest that neuronal seizure activity and systemic inflammation are increased in severe PE. In addition, MgSO treatment reduced systemic inflammation and seizure severity. We conclude that excessive systemic inflammation in PE promotes eclampsia seizures, which can be attenuated by MgSO treatment.

Changes in the Expression of AQP4 and AQP9 in the Hippocampus Following Eclampsia-Like Seizure

“…Based on the classical PE models (LPS infusion) established by Fass et al [ 21 ], we used intraperitoneal injection of PTZ (40 mg/kg body weight) to induce seizures to set an eclampsia-like model to be used in the subsequent studies in order to fully investigate the mechanisms underlying PE and E, and we would try to apply other models. By using PTZ-induced rat models, our previous studies suggested that excessive systemic inflammation and increased brain inflammation in pre-eclampsia decreased the eclampsia-like seizure threshold [ 22 , 39 ], and seizures further increased brain inflammation [ 5 ]. We also found that the number of activated microglia cells and astrocytes in the CA1 area was higher in the pre-eclampsia group than in the normal pregnancy group; this number continued to increase in the eclampsia group [ 5 ].…”

Prenatal intake of omega‐3 promotes Wnt/β‐catenin signaling pathway, and preserves integrity of the blood–brain barrier in preeclamptic rats

“…Shielded, low-weight, flexible cables, connecting the electrodes to the input dual bioamplifier (ml408; dbs337) was attached to examined rat. EEG was recorded on signal channel (channel1:source channel) with low-frequency filter (LFF) of 0.1 Hz and high-frequency filter (HFF) of 60 Hz with sampling rate of 1 KHz (Liu et al, 2016).…”

The role of interleukins in preeclampsia: A comprehensive review

“…It is interesting that a study using an ex vivo placental perfusion system showed that IL‐1β and IL‐1Ra secretion into maternal circulation is increased in PE and is attenuated after the administration of MgSO 4 , proposing thus a possible mechanism of action of this anticonvulsive agent in the disease . The same effect was also observed in a study of a lipopolysaccharide (LPS)‐treated rat model of PE, which indicated that serum levels of IL‐1β were elevated in preeclamptic pregnancies and decreased significantly after treatment with MgSO 4 …”