2022
Preclinical development of an EP2 antagonist for post-seizure cognitive deficits
Varvel N, Amaradhi R, Espinosa-Garcia C, Duddy S, Franklin R, Banik A, Alemán-Ruiz C, Blackmer-Raynolds L, Wang W, Honore T, Ganesh T, Dingledine R. Preclinical development of an EP2 antagonist for post-seizure cognitive deficits. Neuropharmacology 2022, 224: 109356. PMID: 36460083, PMCID: PMC9894535, DOI: 10.1016/j.neuropharm.2022.109356.Peer-Reviewed Original ResearchConceptsCognitive deficitsStatus epilepticusY-maze performanceInvestigational new drugEP2 antagonistComorbidities of epilepsyReduced delayed mortalityY-mazeCognitive comorbiditiesBlood-brain barrier leakageDays of oral administrationCOX-2 inductionSigns of toxicityDeficitsIn vitro studiesEP2 receptorReceptor modulatorsDose linearityProstaglandin E2Neuronal injuryPreclinical developmentOral administrationPreventive treatmentHistopathological signsCyclooxygenase-2
2020
Peripheral Myeloid Cell EP2 Activation Contributes to the Deleterious Consequences of Status Epilepticus
Varvel N, Espinosa-Garcia C, Hunter-Chang S, Chen D, Biegel A, Hsieh A, Blackmer-Raynolds L, Ganesh T, Dingledine R. Peripheral Myeloid Cell EP2 Activation Contributes to the Deleterious Consequences of Status Epilepticus. Journal Of Neuroscience 2020, 41: 1105-1117. PMID: 33293358, PMCID: PMC7880294, DOI: 10.1523/jneurosci.2040-20.2020.Peer-Reviewed Original ResearchConceptsBlood-brain barrierImmune myeloid cellsEP2 receptorInnate immune cellsStatus epilepticusEP2 antagonismProstaglandin EP2 receptorBlood-borne monocytesMyeloid cellsImmune cellsConsequences of seizuresBrain infiltrationInflammatory cytokinesFormation of inflammatory cytokinesConditional KOInflammatory responsePeripheral innate immune cellsActivation of EP2 receptorsQuality of lifeEP2 receptor antagonistRecruitment of blood-borne monocytesSerum albumin levelPeripheral immune cellsConsequences of status epilepticusHippocampal IL-6