Experimental Preeclampsia Causes Persistent Impairment of Hippocampal‐Dependent Memory and Network Function that is Exacerbated by Status Convulsions
Authors: Johnson Abbie C. , Li Zhaojin , Orfila James E. , Herson Paco S. , Cipolla Marilyn J. 
Published: April 2020

Preeclampsia (PE) is a hypertensive disorder of pregnancy involving hyperlipidemia and widespread maternal endothelial dysfunction that can cause spontaneous seizures including status convulsions known as eclampsia. Further, PE increases the risk of cardiovascular disease and cognitive impairment later in life. This study investigated long‐lasting effects of PE without and with status convulsions on the hippocampus, a brain region involved in memory and cognition. Sprague Dawley rats that were either normal pregnant or with experimental PE (ePE) induced by a high cholesterol diet starting d7 of gestation were used. Acute status convulsions were induced on day 19 of a 22‐day gestation via multiple i.p. injections of the chemoconvulsant pentylenetetrazol or saline (no‐seizure controls). Five weeks after status convulsions, an object recognition task was used to quantify the percent of time spent investigating a novel object as a measure of long‐term memory function (n = 8/group). After which, hippocampal network function was assessed by evoking long‐term potentiation (LTP), a well‐accepted cellular model for learning and memory, in the Schaffer Collateral to CA1 (Sch‐CA1) pathway of hippocampal slices. Synaptically evoked field excitatory post‐synaptic potentials (fEPSPs) were collected from the Sch–CA1 area of the hippocampus at a rate of 0.05 Hz. A 20 min stable baseline period was established before delivering a 40 pulse theta burst stimulation (TBS). Increase in fEPSP slope 60 min after TBS was analyzed as a measure of synaptic LTP. Data are mean ± SEM and comparisons made via a two‐way ANOVA to determine the interaction between two independent variables (ePE and status convulsions) with a post‐hoc Tukey test.

There were significant interactions between the effects of ePE and status convulsions on memory function (F (1, 18) = 9.469; p = 0.007) as well as LTP (F (1, 19) = 9.991; p = 0.005). Object recognition was reduced in rats that had ePE compared to those that had a normal pregnancy, as formerly ePE rats spent 55 ± 3 % of the time investigating the novel object, much less than the 73 ± 3 % in rats that had a healthy pregnancy (Fig
). Status convulsions impaired memory in rats that had a normal pregnancy, but not in the ePE group likely due to memory already being impaired (Fig
). Further, LTP was impaired in rats that had ePE, with the slope of fEPSPs increasing to only 132 ± 7 % of baseline in slices from ePE rats compared to 157 ± 4 % in rats that had a healthy pregnancy (Fig
). Status convulsions impaired LTP in rats that had ePE and those that had a normal pregnancy, with the slope of fEPSPs increasing to only 114 ± 5 % of baseline in formerly ePE rats and 106 ± 5 % in rats that had seizures during normal pregnancy (Fig
).

Overall, these findings suggest that PE and eclampsia cause permanent memory dysfunction by impairing LTP in the hippocampus, and highlight the importance of seizure prevention to maternal cognitive health. Further, understanding mechanisms of impaired hippocampal plasticity after PE and/or eclampsia may lead to novel therapeutic approaches to minimize the cognitive burden associated with PE and eclampsia later in life.

Support or Funding Information

NIH NINDS R01 NS045940NIH NINDS R01 NS108455

Long‐term memory as measured via a novel object recognition task. **p<0.01.

Figure 1

LTP of hippocampal slices. *p<0.05 and **p<0.01.

Figure 2