CD4+T Cells From Preeclamptic Patients During Pregnancy Causes Cognitive Dysfunction Postpartum In A Pregnant Rat Model

Preeclampsia (PE), new onset hypertension (HTN) during pregnancy, is associated with impaired cognitive function and increased cerebral blood flow (CBF). Although we have previously shown adoptive transfer of placental CD4+ T cells from PE women into athymic nude pregnant rats causes HTN and circulating factors associated with PE, we do not know the role of CD4+ T cells in contributing to impaired cerebral blood flow and cognitive dysfunction in the postpartum period. Therefore, we hypothesize that adoptive transfer of placental CD4+ T cells from PE patients into pregnant athymic nude recipient rats will cause maternal hypertension and cognitive dysfunction and impaired CBF postpartum. Placental CD4+ T cells were isolated from normotensive (NP) and preeclamptic (PE) pregnant women at delivery. One million CD4+ T cells were injected interperitoneally (i.p.) into normal pregnant nude athymic rats on gestational day (GD) 12. Dams were allowed to deliver and aged 12-weeks after delivery. Blood pressure (MAP) was measured by carotid catheter and at 12-weeks postpartum CBF autoregulation was measured by laser Doppler flowmetry. The Barnes maze and the novel object recognition behavioral assays were used to assess cognitive function on gestational day (GD) 15-19 and 12-weeks postpartum. A student’s t-test was used for statistical analysis. MAP increased during pregnancy in PE recipient rats (115±2 mmHg, n=5) compared to NP recipient rats (99±3 mmHg, n=4, p< 0.05). MAP significantly increased in the postpartum period in PE recipient rats (114±2 mmHg, n=5) compared to NP controls (98±2 mmHg, n=7, p<0.05). PE recipient rats exhibited latency with errors navigating in the Barnes maze compared to NP controls during pregnancy and postpartum. Locomotor activity was decreased in PE recipient rats compared to NP controls during pregnancy (p<0.05) and postpartum. PE recipient rats had increased CBF autoregulation compared to NP rat recipients in the postpartum period. Our findings indicate that rat recipients of CD4+ T cells from PE patients demonstrate maternal HTN and increased CBF and cognitive dysfunction in the postpartum period compared to recipients of NP CD4 + T cells. These data indicate long-term cognitive and cerebral dysfunction as a result of preeclampsia.