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  • Title: A rat model of organophosphate-induced status epilepticus and the beneficial effects of EP2 receptor inhibition.
    Author: Rojas A, Ganesh T, Wang W, Wang J, Dingledine R.
    Journal: Neurobiol Dis; 2020 Jan; 133():104399. PubMed ID: 30818067.
    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.
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