A rat model of organophosphate-induced status epilepticus and the beneficial effects of EP2 receptor inhibition
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...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-01-01
|
| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996119300427 |
| _version_ | 1823944382680662016 |
|---|---|
| author | Asheebo Rojas Thota Ganesh Wenyi Wang Jennifer Wang Raymond Dingledine |
| author_facet | Asheebo Rojas Thota Ganesh Wenyi Wang Jennifer Wang Raymond Dingledine |
| author_sort | Asheebo Rojas |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T08:09:44Z |
| format | Article |
| id | doaj.art-9bf417baf60e45f2a228193172e4da9a |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T08:09:44Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-9bf417baf60e45f2a228193172e4da9a2022-12-21T21:57:15ZengElsevierNeurobiology of Disease1095-953X2020-01-01133A rat model of organophosphate-induced status epilepticus and the beneficial effects of EP2 receptor inhibitionAsheebo Rojas0Thota Ganesh1Wenyi Wang2Jennifer Wang3Raymond Dingledine4Corresponding author.; Department of Pharmacology, Emory University, 1510 Clifton Road NE, Atlanta, GA 30322, USADepartment of Pharmacology, Emory University, 1510 Clifton Road NE, Atlanta, GA 30322, USADepartment of Pharmacology, Emory University, 1510 Clifton Road NE, Atlanta, GA 30322, USADepartment of Pharmacology, Emory University, 1510 Clifton Road NE, Atlanta, GA 30322, USADepartment of Pharmacology, Emory University, 1510 Clifton Road NE, Atlanta, GA 30322, USAThis 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.http://www.sciencedirect.com/science/article/pii/S0969996119300427Diisopropyl fluorophosphateEP2AlbuminAcetylcholinesteraseNeurodegenerationStatus epilepticus |
| spellingShingle | Asheebo Rojas Thota Ganesh Wenyi Wang Jennifer Wang Raymond Dingledine A rat model of organophosphate-induced status epilepticus and the beneficial effects of EP2 receptor inhibition Neurobiology of Disease Diisopropyl fluorophosphate EP2 Albumin Acetylcholinesterase Neurodegeneration Status epilepticus |
| title | A rat model of organophosphate-induced status epilepticus and the beneficial effects of EP2 receptor inhibition |
| title_full | A rat model of organophosphate-induced status epilepticus and the beneficial effects of EP2 receptor inhibition |
| title_fullStr | A rat model of organophosphate-induced status epilepticus and the beneficial effects of EP2 receptor inhibition |
| title_full_unstemmed | A rat model of organophosphate-induced status epilepticus and the beneficial effects of EP2 receptor inhibition |
| title_short | A rat model of organophosphate-induced status epilepticus and the beneficial effects of EP2 receptor inhibition |
| title_sort | rat model of organophosphate induced status epilepticus and the beneficial effects of ep2 receptor inhibition |
| topic | Diisopropyl fluorophosphate EP2 Albumin Acetylcholinesterase Neurodegeneration Status epilepticus |
| url | http://www.sciencedirect.com/science/article/pii/S0969996119300427 |
| work_keys_str_mv | AT asheeborojas aratmodeloforganophosphateinducedstatusepilepticusandthebeneficialeffectsofep2receptorinhibition AT thotaganesh aratmodeloforganophosphateinducedstatusepilepticusandthebeneficialeffectsofep2receptorinhibition AT wenyiwang aratmodeloforganophosphateinducedstatusepilepticusandthebeneficialeffectsofep2receptorinhibition AT jenniferwang aratmodeloforganophosphateinducedstatusepilepticusandthebeneficialeffectsofep2receptorinhibition AT raymonddingledine aratmodeloforganophosphateinducedstatusepilepticusandthebeneficialeffectsofep2receptorinhibition AT asheeborojas ratmodeloforganophosphateinducedstatusepilepticusandthebeneficialeffectsofep2receptorinhibition AT thotaganesh ratmodeloforganophosphateinducedstatusepilepticusandthebeneficialeffectsofep2receptorinhibition AT wenyiwang ratmodeloforganophosphateinducedstatusepilepticusandthebeneficialeffectsofep2receptorinhibition AT jenniferwang ratmodeloforganophosphateinducedstatusepilepticusandthebeneficialeffectsofep2receptorinhibition AT raymonddingledine ratmodeloforganophosphateinducedstatusepilepticusandthebeneficialeffectsofep2receptorinhibition |