186. Seizure-induced cognitive impairment in a rat model of preeclampsia: Effects of multiple seizures and anti-seizure treatments

Abstract

Introduction Eclamptic seizures include tonic-clonic convulsions that can be recurrent and cause acute memory deficits and cognitive impairment. While a brief seizure may cause minimal injury, recurrent seizures can impair memory and cognition. In addition, whether preeclampsia (PE) increases the susceptibility to seizure-induced cognitive impairment, or if anti-seizure treatments are protective remains unclear. Objective/Hypothesis We tested the hypothesis that multiple seizures would cause greater memory impairment than a single seizure in PE versus normal pregnancy, and compared the protective effects of magnesium sulfate ( MgSO 4 ) and diazepam (Dz) on seizure-induced cognitive dysfunction. Methods Pregnant (d19-20) Sprague Dawley rats were normal (Preg) or with PE (induced by a high cholesterol diet gestational d7-20). The chemoconvulsant pentylenetetrazol (PTZ; i.p.) was used to compare the effect of one versus multiple tonic–clonic seizures on cognition. Rats either received one PTZ injection (60 mg/kg; n = 6/group), multiple PTZ injections (5–40 mg/kg; n = 13/group), or vehicle (CTL; n = 7/group). Rats having seizure(s) received MgSO 4 (270 mg/kg i.p.) or Dz (10 mg/kg i.p.) 20 min after PTZ. Short-term memory was tested 24 h post-seizures using a novel object recognition task, and recognition index calculated: (novel object time)/(total object time). Data are mean ± SEM and comparisons made using a Student’s t-test. Results Preg and PE rats that had multiple seizures had decreased recognition indices compared to CTL (0.49 ± 0.04 vs. 0.69 ± 0.06, p 0.05 and 0.46 ± 0.07 vs. 0.70 ± 0.05, p 0.05) that was unaffected by MgSO 4 or Dz in PE rats (0.49 ± 0.12 and 0.42 ± 0.08, respectively) and Preg rats (0.46 ± 0.08 and 0.51 ± 0.04, respectively). A single seizure did not affect short-term memory in either group. Discussion Cognitive function was significantly impaired after multiple seizures in both Preg and PE rats; however, a single seizure did not affect memory function. Neither MgSO 4 nor Dz treatment improved cognition after multiple seizures, highlighting the importance of prevention of eclampsia and seizure cessation to maternal cognitive health.