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Literature DB >> 30818067

A rat model of organophosphate-induced status epilepticus and the beneficial effects of EP2 receptor inhibition.

Asheebo Rojas¹, Thota Ganesh², Wenyi Wang², Jennifer Wang², Raymond Dingledine².

Abstract

This review describes an adult rat model of status epilepticus (SE) induced by diisopropyl fluorophosphate (DFP), and the beneficial outcomes of transient inhibition of the prostaglandin-E2 receptor EP2 with a small molecule antagonist, delayed by 2-4 h after SE onset. Administration of six doses of the selective EP2 antagonist TG6-10-1 over a 2-3 day period accelerates functional recovery, attenuates hippocampal neurodegeneration, neuroinflammation, gliosis and blood-brain barrier leakage, and prevents long-term cognitive deficits without blocking SE itself or altering acute seizure characteristics. This work has provided important information regarding organophosphate-induced seizure related pathologies in adults and revealed the effectiveness of delayed EP2 inhibition to combat these pathologies.

Entities: CellLine Chemical Disease Gene Species

Keywords: Acetylcholinesterase; Albumin; Cyclooxygenase-2; Diisopropyl fluorophosphate; EP2; Neurodegeneration; Neuroinflammation; Organophosphorus; Status epilepticus

Mesh：

Substances：

Year: 2019 PMID： 30818067 PMCID： PMC6708729 DOI： 10.1016/j.nbd.2019.02.010

Source DB: PubMed Journal: Neurobiol Dis ISSN： 0969-9961 Impact factor: 5.996

81 in total

1. COX-2, a synaptically induced enzyme, is expressed by excitatory neurons at postsynaptic sites in rat cerebral cortex.

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Journal: Proc Natl Acad Sci U S A Date: 1996-03-19 Impact factor: 11.205

2. Neuroprotective Effects of AEOL10150 in a Rat Organophosphate Model.

Authors: Li-Ping Liang; Jennifer N Pearson-Smith; Jie Huang; Pallavi McElroy; Brian J Day; Manisha Patel
Journal: Toxicol Sci Date: 2018-04-01 Impact factor: 4.849

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4. Benzodiazepine-refractory status epilepticus, neuroinflammation, and interneuron neurodegeneration after acute organophosphate intoxication.

Authors: Ramkumar Kuruba; Xin Wu; Doodipala Samba Reddy
Journal: Biochim Biophys Acta Mol Basis Dis Date: 2018-05-23 Impact factor: 5.187

5. Editor's Highlight: Spatiotemporal Progression and Remission of Lesions in the Rat Brain Following Acute Intoxication With Diisopropylfluorophosphate.

Authors: Sílvia Sisó; Brad A Hobson; Danielle J Harvey; Donald A Bruun; Douglas J Rowland; Joel R Garbow; Pamela J Lein
Journal: Toxicol Sci Date: 2017-06-01 Impact factor: 4.849

6. Small molecule antagonist reveals seizure-induced mediation of neuronal injury by prostaglandin E2 receptor subtype EP2.

Authors: Jianxiong Jiang; Thota Ganesh; Yuhong Du; Yi Quan; Geidy Serrano; Min Qui; Iris Speigel; Asheebo Rojas; Nadia Lelutiu; Raymond Dingledine
Journal: Proc Natl Acad Sci U S A Date: 2012-02-08 Impact factor: 11.205

Review 7. Models to identify treatments for the acute and persistent effects of seizure-inducing chemical threat agents.

Authors: Isaac N Pessah; Michael A Rogawski; Daniel J Tancredi; Heike Wulff; Dorota Zolkowska; Donald A Bruun; Bruce D Hammock; Pamela J Lein
Journal: Ann N Y Acad Sci Date: 2016-07-28 Impact factor: 5.691

8. Prevention of seizure-induced up-regulation of endothelial P-glycoprotein by COX-2 inhibition.

Authors: Guido Zibell; Bernadette Unkrüer; Anton Pekcec; Anika M S Hartz; Björn Bauer; David S Miller; Heidrun Potschka
Journal: Neuropharmacology Date: 2009-01-21 Impact factor: 5.250

9. Direct microinjection of soman or VX into the amygdala produces repetitive limbic convulsions and neuropathology.

Authors: J H McDonough; C G McLeod; M T Nipwoda
Journal: Brain Res Date: 1987-12-01 Impact factor: 3.252

10. Beneficial Outcome of Urethane Treatment Following Status Epilepticus in a Rat Organophosphorus Toxicity Model.

Authors: Asheebo Rojas; Wenyi Wang; Avery Glover; Zahra Manji; Yujiao Fu; Raymond Dingledine
Journal: eNeuro Date: 2018-04-17

19 in total

1. Urethane attenuates early neuropathology of diisopropylfluorophosphate-induced status epilepticus in rats.

Authors: Asheebo Rojas; Jennifer Wang; Avery Glover; Raymond Dingledine
Journal: Neurobiol Dis Date: 2020-04-10 Impact factor: 5.996

2. Diapocynin, an NADPH oxidase inhibitor, counteracts diisopropylfluorophosphate-induced long-term neurotoxicity in the rat model.

Authors: Marson Putra; Meghan Gage; Shaunik Sharma; Cara Gardner; Grace Gasser; Vellareddy Anantharam; Thimmasettappa Thippeswamy
Journal: Ann N Y Acad Sci Date: 2020-02-10 Impact factor: 5.691

3. Second-Generation Prostaglandin Receptor EP2 Antagonist, TG8-260, with High Potency, Selectivity, Oral Bioavailability, and Anti-Inflammatory Properties.

Authors: Radhika Amaradhi; Shabber Mohammed; Avijit Banik; Ronald Franklin; Raymond Dingledine; Thota Ganesh
Journal: ACS Pharmacol Transl Sci Date: 2022-01-25

4. Pharmacological antagonism of EP2 receptor does not modify basal cardiovascular and respiratory function, blood cell counts, and bone morphology in animal models.

Authors: Varun Rawat; Avijit Banik; Radhika Amaradhi; Asheebo Rojas; Shashidharamurthy Taval; Tamas Nagy; Raymond Dingledine; Thota Ganesh
Journal: Biomed Pharmacother Date: 2022-01-26 Impact factor: 6.529

5. Preface: Discovery and development of better medical countermeasures for chemical threats targeting the nervous system.

Authors: David A Jett; Aristea S Galanopoulou; Solomon L Moshé
Journal: Neurobiol Dis Date: 2019-07-30 Impact factor: 5.996