Hippocampal network dysfunction as a mechanism of early-onset dementia after preeclampsia and eclampsia

Abstract

Preeclampsia is a hypertensive disorder of pregnancy that can involve dangerous neurological symptoms such as spontaneous seizures (eclampsia). Despite being diseases specific to the pregnant state, preeclampsia and eclampsia have long-lasting neurological consequences later in life, including changes in brain structure and cognitive decline at relatively young ages. However, the effects of preeclampsia on brain regions central to memory and cognition, such as the hippocampus, are unclear. Here, we present a case reporting the progressive and permanent cognitive decline in a woman that had eclamptic seizures in the absence of evidence of brain injury on MRI. We then use rat models of normal pregnancy and preeclampsia to investigate mechanisms by which eclampsia-like seizures may disrupt hippocampal function. We show that experimental preeclampsia causes delayed memory decline in rats and disruption of hippocampal neuroplasticity. Further, seizures in pregnancy and preeclampsia caused acute memory dysfunction and impaired neuroplasticity but did not cause acute neuronal cell death. Importantly, hippocampal dysfunction persisted 5 weeks postpartum, suggesting seizure-induced injury is long lasting and may be permanent. Our data provide the first evidence of a model of preeclampsia that may mimic the cognitive decline of formerly preeclamptic women, and that preeclampsia and eclampsia affect hippocampal network plasticity and impair memory.