PMID- 34815190 OWN - NLM STAT- MEDLINE DCOM- 20220322 LR - 20220322 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 101 IP - Pt B DP - 2021 Dec TI - Acetylcholinesterase inhibition with Pyridostigmine attenuates hypertension and neuroinflammation in the paraventricular nucleus in rat model for Preeclampsia. PG - 108365 LID - S1567-5769(21)01001-8 [pii] LID - 10.1016/j.intimp.2021.108365 [doi] AB - Preeclampsia (PE) is characterized by hypertension, autonomic imbalance and inflammation. The subfornical organ (SFO) reportedly relays peripheral inflammatory mediator's signals to the paraventricular nucleus (PVN), a brain autonomic center shown to mediate hypertension in hypertensive rat but not yet in PE rat models. Additionally, we previously showed that Pyridostigmine (PYR), an acetylcholinesterase inhibitor, attenuated placental inflammation and hypertension in PE models. In this study, we investigated the effect of PYR on the activities of these brain regions in PE model. PYR (20 mg/kg/day) was administered to reduced uterine perfusion pressure (RUPP) Sprague-Dawley rat from gestational day (GD) 14 to GD19. On GD19, the mean arterial pressure (MAP) was recorded and samples were collected for analysis. RUPP rats exhibited increased MAP (P = 0.0025), elevated circulating tumor necrosis factor-alpha (TNF-alpha, P = 0.0075), reduced baroreflex sensitivity (BRS), increased neuroinflammatory markers including TNF-alpha, interleukin-1beta (IL-1beta), microglial activation (P = 0.0039), oxidative stress and neuronal excitation within the PVN and the SFO. Changes in MAP, in molecular and cellular expression induced by RUPP intervention were improved by PYR. The ability of PYR to attenuate TNF-alpha mediated central effect was evaluated in TNF-alpha-infused pregnant rats. TNF-alpha infusion-promoted neuroinflammation in the PVN and SFO in dams was abolished by PYR. Collectively, our data suggest that PYR improves PE-like symptoms in rat by dampening placental ischemia and TNF-alpha-promoted inflammation and pro-hypertensive activity in the PVN. This broadens the therapeutical potential of PYR in PE. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - Issotina Zibrila, Abdoulaye AU - Issotina Zibrila A AD - Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases, Xi'an 710061, Shaanxi, PR China. FAU - Li, Yubei AU - Li Y AD - School of Clinical Medicine, Xi'an Medical University, Xi'an 710021, Shaanxi, PR China. FAU - Wang, Zheng AU - Wang Z AD - Department of Pharmacology, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an 710061, Shaanxi, PR China. FAU - Zhao, Gongxiao AU - Zhao G AD - Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases, Xi'an 710061, Shaanxi, PR China. FAU - Liu, Haotian AU - Liu H AD - Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases, Xi'an 710061, Shaanxi, PR China. FAU - Leng, Jing AU - Leng J AD - Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases, Xi'an 710061, Shaanxi, PR China. FAU - Ahasan Ali, Md AU - Ahasan Ali M AD - Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases, Xi'an 710061, Shaanxi, PR China. FAU - Ampofo Osei, James AU - Ampofo Osei J AD - Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases, Xi'an 710061, Shaanxi, PR China. FAU - Kang, Yu-Ming AU - Kang YM AD - Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases, Xi'an 710061, Shaanxi, PR China. Electronic address: ykang@mail.xjtu.edu.cn. FAU - Liu, Jinjun AU - Liu J AD - Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases, Xi'an 710061, Shaanxi, PR China. Electronic address: jupet.1128@mail.xjtu.edu.cn. LA - eng PT - Journal Article DEP - 20211121 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Bacterial Proteins) RN - 0 (Biomarkers) RN - 0 (Cholinesterase Inhibitors) RN - 0 (SpaG protein, Bacillus subtilis) RN - 0 (Tumor Necrosis Factor-alpha) RN - KVI301NA53 (Pyridostigmine Bromide) SB - IM MH - ATP-Binding Cassette Transporters MH - Animals MH - Bacterial Proteins MH - Baroreflex/drug effects MH - Biomarkers/metabolism MH - Blood Pressure/drug effects MH - Cholinesterase Inhibitors/*pharmacology MH - Female MH - Heart Rate/drug effects MH - Hypertension/*drug therapy MH - Neuroinflammatory Diseases/*drug therapy MH - Oxidative Stress/drug effects MH - Paraventricular Hypothalamic Nucleus/*drug effects MH - Pre-Eclampsia/*drug therapy MH - Pregnancy MH - Pyridostigmine Bromide/*pharmacology MH - Random Allocation MH - Rats MH - Tumor Necrosis Factor-alpha/administration & dosage/toxicity OTO - NOTNLM OT - Microglial activation OT - Neuroinflammation OT - Paraventricular nucleus OT - Preeclampsia OT - Pyridostigmine OT - Reduced Uterine Perfusion Pressure EDAT- 2021/11/25 06:00 MHDA- 2022/03/23 06:00 CRDT- 2021/11/24 05:45 PHST- 2021/09/26 00:00 [received] PHST- 2021/10/30 00:00 [revised] PHST- 2021/11/09 00:00 [accepted] PHST- 2021/11/25 06:00 [pubmed] PHST- 2022/03/23 06:00 [medline] PHST- 2021/11/24 05:45 [entrez] AID - S1567-5769(21)01001-8 [pii] AID - 10.1016/j.intimp.2021.108365 [doi] PST - ppublish SO - Int Immunopharmacol. 2021 Dec;101(Pt B):108365. doi: 10.1016/j.intimp.2021.108365. Epub 2021 Nov 21.