Acid Sensing Ion Channel 2a Is Reduced in the Reduced Uterine Perfusion Pressure Mouse Model and Increases Seizure Susceptibility in Pregnant Mice

Eclampsia is diagnosed in pregnant women who develop novel seizures. Our laboratory showed that the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia displays reduced latency to drug-induced seizures. While acid sensing ion channels (ASIC1a and 3) are important for reducing seizure longevity and severity, the role of ASIC2a in mediating seizure sensitivity in pregnancy has not been investigated. We hypothesized that 1) RUPP reduces hippocampal ASIC2a, and 2) pregnant mice with reduced ASIC2a (ASIC2a+/−) have increased seizure sensitivity. On gestational day 18.5, hippocampi from sham and RUPP C57BL/6 mice were harvested, and ASIC2a was assessed using Western blot. Pregnant wild-type and ASIC2a+/− mice received 40 mg/kg of pentylenetetrazol (i.p.) and were video recorded for 30 min. Behaviors were scored using a modified Racine scale (0–7: 0 = no seizure; 7 = respiratory arrest/death). Seizure severity was classified as mild (score = 1–3) or severe (score = 4–7). RUPP mice had reduced hippocampal and placental ASIC2a protein. ASIC2a+/− mice had reduced latency to seizures, increased seizure duration, increased severe seizure duration, and higher maximum seizure scores. Reduced hippocampal ASIC2a in RUPP mice and increased seizure activity in pregnant ASIC2a+/− mice support the hypothesis that reduced ASIC2a increases seizure sensitivity associated with the RUPP.

Principles of Pharmacotherapy of Seizures and Status Epilepticus

Status epilepticus is a neurological emergency with an outcome that is highly associated with the initial pharmacotherapy management that must be administered in a timely fashion. Beyond first-line therapy of status epilepticus, treatment is not guided by robust evidence. Optimal pharmacotherapy selection for individual patients is essential in the management of seizures and status epilepticus with careful evaluation of pharmacokinetic and pharmacodynamic factors. With the addition of newer antiseizure agents to the market, understanding their role in the management of status epilepticus is critical. Etiology-guided therapy should be considered in certain patients with drug-induced seizures, alcohol withdrawal, or autoimmune encephalitis. Some patient populations warrant special consideration, such as pediatric, pregnant, elderly, and the critically ill. Seizure prophylaxis is indicated in select patients with acute neurological injury and should be limited to the acute postinjury period.