- Email: [email protected]
80 Nicotine increases eclampsia-like seizure threshold and attenuates microglial activity in rat hippocampus through the A7 nicotinic acetylcholine receptor
216
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 6 (2016) 178–252
Basic science 79 sFlt-1 and miRNA-210 expressions have strong correlation in preeclamptic placentas Biomarkers, prediction of preeclampsia Henri Augusto Korkes a, Leandro Gustavo de oliveira a, Nelson Sass a, S. Ananth Karumanchi b, Augustine Rajakumar b (a UNIFESP, Sao Paulo, SP, Brazil, b Harvard, Boston, United States) Introduction: Preeclampsia (PE) is a multifactor disease responsible for enormous amount of maternal and perinatal mortality worldwide. The growing knowledge about the disease has highlighted several biomarkers that may act in synergistic ways in the pathogenesis of PE, mainly the anti-angiogenic factor sFlt-1. Recently, some authors have demonstrated the involvement of the angiogenic microRNA-210 (miR-210) in the development of PE. Objective: Our aims for this study were to re-evaluate the expression of sFlt-1 and miR-210 by preeclamptic placentas and determine any correlation between these two biomarkers. Methods: Placentas were collected from normal and preeclamptic patients (n = 11 in each group). These tissue samples were flashfrozen in liquid nitrogen within half an hour of placental delivery. Total RNA was extracted using the acid guanidinium thiocyanate–p henol–chloroform extraction technique and their concentrations were determined using spectrophotometer. qRT-PCR was performed for the quantitation of Flt1, sFlt13, sFlt14 and miR-210. Results: The mRNA expression of sFlt-1 and miR-210 in PE and controls were respectively (14.70–1.047) and (2.737–1.125). We also identified a strong correlation between sFlt-1 and miR-210 (R2 = 0.7967, p < 0.0001). Conclusion: Our results confirm previous observations regarding the increased mRNA expressions of sFlt-1 and miRNA-210 by preeclamptic placentas and highlight the dysregulation of the angiogenic process in the pathogenesis of PE. doi:10.1016/j.preghy.2016.08.161
Basic science 80 Nicotine increases eclampsia-like seizure threshold and attenuates microglial activity in rat hippocampus through the A7 nicotinic acetylcholine receptor Immune and inflammatory mechanisms Xiaolan Li, Xinjia Han, Junjie Bao, Yuanyuan Liu, Aihua Ye, Guozheng Zhang, Huishu Liu (Guangzhou Women and Children’s Medical Center, Guangzhou, China) Introduction: A considerable number of studies have demonstrated that nicotine, a a7-nicotinic acetylcholine receptor (a7-nAChR) agonist, can dampen immune response through the cholinergic anti-inflammatory pathway. Evidence suggests that inflammation plays a critical role in eclampsia, which contributes to maternal and fetal morbidity and mortality. Objectives: In the present study, possible anti-inflammation and neuro-protective effects of nicotine via a7-nAChRs have been investigated after inducing eclampsia-like seizures in rats. Methods: Rat eclampsia-like models were established by administering lipopolysaccharide (LPS) plus pentylenetetrazol (PTZ) in pregnant rats. Rats were given nicotine from gestation day (GD) 14–19. Then, clinical symptoms were detected. Seizure severity was
recorded by behavioral tests, serum levels of inflammatory cytokines were measured by Luminex assays, microglia and astrocyte expressions were detected by immunofluorescence, and changes in neuronal number in the hippocampal CA1 region among different groups were detected by Nissl staining. Results: Our results revealed that nicotine effectively improved fetal outcomes. Furthermore, it significantly decreased systolic blood pressure, and maternal serum levels of Th1 cytokines (TNF-a, IL-1b, IL-6 and IL-12P70) and an IL-17 cytokine (IL-17A), dramatically increased Th1 cytokine (IL-4) and eclampsia-like seizure threshold. Moreover, this attenuated neuronal loss and decreased the expression of microglial activation markers of the hippocampal CA1 region in the eclampsia-like group. Additionally, pretreatment with a-bungarotoxin, a selective a7-nAChR antagonist could prevent the protective effects of nicotine in eclampsia-like model rats. Conclusion: Our findings indicate that the administration of nicotine may increase eclampsia-like seizure threshold and attenuate microglial activity in rat hippocampus through the a7 nicotinic receptor. doi:10.1016/j.preghy.2016.08.162
Clinical science 81 Postpartum physiology, psychology and paediatric study – P4 study Long term consequences for mother and child Greg K. Davis, Lynne Roberts, Amanda Henry, Franziska Pettit, Tony O’sullivan, Caroline S.E. Homer, Maria Craig, George Mangos, Samuel B. Harvey, Mark A. Brown (St George Hospital, Sydney, Australia) Background: Women who have had hypertension in pregnancy are at greater risk of future cardiovascular disease. Little is known about their cardiovascular risk postpartum or the effects of hypertensive pregnancy on a woman’s mental health and the outcomes of her infant. Aims: In this project we are studying the physiological and psychological health of women and the physical health and development of their infants six months, two years and five years after birth. We will establish normal ranges for women who were normotensive in pregnancy and compare these in women who had gestational hypertension (GH) or preeclampsia (PE). Methods: Women are asked to participate if they have given birth in the preceding six months. Exclusion criteria include diabetes mellitus, chronic hypertension, renal or other serious maternal disease prior to pregnancy or congenital anomaly in the pregnancy. Recruitment has commenced for 300 women with prior normotensive pregnancy, 100 who had PE and 100 who had GH, and their babies. They are assessed at six months, two and five years after birth. At each assessment, women have their blood pressure (BP) assessed peripherally with a manual liquid crystal sphygmomanometer and 24 h ambulatory blood pressure monitoring, and centrally with non-invasive applanation tonometry. Additional physiological testing includes: body composition; energy balance; vascular compliance; cardiac function; liver and renal function, lipids and biochemistry; glucose and insulin; and urinalysis. Psychological status is assessed using validated self-report questionnaires for depression, anxiety, posttraumatic stress disorder and mother-infant bonding. The babies are examined by a paediatrician at each assessment. Their behavioural development is assessed with an age appropriate Ages and Stages Questionnaire completed by
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 6 (2016) 178–252
Basic science 79 sFlt-1 and miRNA-210 expressions have strong correlation in preeclamptic placentas Biomarkers, prediction of preeclampsia Henri Augusto Korkes a, Leandro Gustavo de oliveira a, Nelson Sass a, S. Ananth Karumanchi b, Augustine Rajakumar b (a UNIFESP, Sao Paulo, SP, Brazil, b Harvard, Boston, United States) Introduction: Preeclampsia (PE) is a multifactor disease responsible for enormous amount of maternal and perinatal mortality worldwide. The growing knowledge about the disease has highlighted several biomarkers that may act in synergistic ways in the pathogenesis of PE, mainly the anti-angiogenic factor sFlt-1. Recently, some authors have demonstrated the involvement of the angiogenic microRNA-210 (miR-210) in the development of PE. Objective: Our aims for this study were to re-evaluate the expression of sFlt-1 and miR-210 by preeclamptic placentas and determine any correlation between these two biomarkers. Methods: Placentas were collected from normal and preeclamptic patients (n = 11 in each group). These tissue samples were flashfrozen in liquid nitrogen within half an hour of placental delivery. Total RNA was extracted using the acid guanidinium thiocyanate–p henol–chloroform extraction technique and their concentrations were determined using spectrophotometer. qRT-PCR was performed for the quantitation of Flt1, sFlt13, sFlt14 and miR-210. Results: The mRNA expression of sFlt-1 and miR-210 in PE and controls were respectively (14.70–1.047) and (2.737–1.125). We also identified a strong correlation between sFlt-1 and miR-210 (R2 = 0.7967, p < 0.0001). Conclusion: Our results confirm previous observations regarding the increased mRNA expressions of sFlt-1 and miRNA-210 by preeclamptic placentas and highlight the dysregulation of the angiogenic process in the pathogenesis of PE. doi:10.1016/j.preghy.2016.08.161
Basic science 80 Nicotine increases eclampsia-like seizure threshold and attenuates microglial activity in rat hippocampus through the A7 nicotinic acetylcholine receptor Immune and inflammatory mechanisms Xiaolan Li, Xinjia Han, Junjie Bao, Yuanyuan Liu, Aihua Ye, Guozheng Zhang, Huishu Liu (Guangzhou Women and Children’s Medical Center, Guangzhou, China) Introduction: A considerable number of studies have demonstrated that nicotine, a a7-nicotinic acetylcholine receptor (a7-nAChR) agonist, can dampen immune response through the cholinergic anti-inflammatory pathway. Evidence suggests that inflammation plays a critical role in eclampsia, which contributes to maternal and fetal morbidity and mortality. Objectives: In the present study, possible anti-inflammation and neuro-protective effects of nicotine via a7-nAChRs have been investigated after inducing eclampsia-like seizures in rats. Methods: Rat eclampsia-like models were established by administering lipopolysaccharide (LPS) plus pentylenetetrazol (PTZ) in pregnant rats. Rats were given nicotine from gestation day (GD) 14–19. Then, clinical symptoms were detected. Seizure severity was
recorded by behavioral tests, serum levels of inflammatory cytokines were measured by Luminex assays, microglia and astrocyte expressions were detected by immunofluorescence, and changes in neuronal number in the hippocampal CA1 region among different groups were detected by Nissl staining. Results: Our results revealed that nicotine effectively improved fetal outcomes. Furthermore, it significantly decreased systolic blood pressure, and maternal serum levels of Th1 cytokines (TNF-a, IL-1b, IL-6 and IL-12P70) and an IL-17 cytokine (IL-17A), dramatically increased Th1 cytokine (IL-4) and eclampsia-like seizure threshold. Moreover, this attenuated neuronal loss and decreased the expression of microglial activation markers of the hippocampal CA1 region in the eclampsia-like group. Additionally, pretreatment with a-bungarotoxin, a selective a7-nAChR antagonist could prevent the protective effects of nicotine in eclampsia-like model rats. Conclusion: Our findings indicate that the administration of nicotine may increase eclampsia-like seizure threshold and attenuate microglial activity in rat hippocampus through the a7 nicotinic receptor. doi:10.1016/j.preghy.2016.08.162
Clinical science 81 Postpartum physiology, psychology and paediatric study – P4 study Long term consequences for mother and child Greg K. Davis, Lynne Roberts, Amanda Henry, Franziska Pettit, Tony O’sullivan, Caroline S.E. Homer, Maria Craig, George Mangos, Samuel B. Harvey, Mark A. Brown (St George Hospital, Sydney, Australia) Background: Women who have had hypertension in pregnancy are at greater risk of future cardiovascular disease. Little is known about their cardiovascular risk postpartum or the effects of hypertensive pregnancy on a woman’s mental health and the outcomes of her infant. Aims: In this project we are studying the physiological and psychological health of women and the physical health and development of their infants six months, two years and five years after birth. We will establish normal ranges for women who were normotensive in pregnancy and compare these in women who had gestational hypertension (GH) or preeclampsia (PE). Methods: Women are asked to participate if they have given birth in the preceding six months. Exclusion criteria include diabetes mellitus, chronic hypertension, renal or other serious maternal disease prior to pregnancy or congenital anomaly in the pregnancy. Recruitment has commenced for 300 women with prior normotensive pregnancy, 100 who had PE and 100 who had GH, and their babies. They are assessed at six months, two and five years after birth. At each assessment, women have their blood pressure (BP) assessed peripherally with a manual liquid crystal sphygmomanometer and 24 h ambulatory blood pressure monitoring, and centrally with non-invasive applanation tonometry. Additional physiological testing includes: body composition; energy balance; vascular compliance; cardiac function; liver and renal function, lipids and biochemistry; glucose and insulin; and urinalysis. Psychological status is assessed using validated self-report questionnaires for depression, anxiety, posttraumatic stress disorder and mother-infant bonding. The babies are examined by a paediatrician at each assessment. Their behavioural development is assessed with an age appropriate Ages and Stages Questionnaire completed by