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
Stroke-Induced Peripheral Immune Dysfunction in Vitamin D–Deficient Conditions: Modulation by Progesterone and Vitamin D
Yousuf S, Atif F, Espinosa-Garcia C, Harris W, Turan N, Stein D. Stroke-Induced Peripheral Immune Dysfunction in Vitamin D–Deficient Conditions: Modulation by Progesterone and Vitamin D. Molecular Neurobiology 2020, 58: 950-963. PMID: 33063282, DOI: 10.1007/s12035-020-02129-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisAstrocytesBehavior, AnimalBiomarkersCyclooxygenase 2Endoplasmic Reticulum StressHand StrengthInflammationInflammation MediatorsInterleukin-6LipopolysaccharidesMaleMyelin Basic ProteinNeuronsNitric Oxide Synthase Type IIProgesteroneRatsRats, Sprague-DawleyReactive Oxygen SpeciesReproducibility of ResultsSpleenStrokeThymus GlandTranscription Factor CHOPVitamin DVitamin D DeficiencyWhite MatterConceptsPeripheral immune dysfunctionSystemic inflammationImmune dysfunctionCombined treatmentLipopolysaccharide (LPS)-induced systemic inflammationVitamin D. Vitamin D deficiencyImmune cell populationsAdministration of progesteroneVitamin D-deficient conditionDelayed functional recoveryD sufficiencyD deficiencyEndoplasmic reticulum stressTreated with PVitamin DWhite matter integrityComorbid conditionsDay 4Improve outcomesFunctional recoveryAltered outcomesInflammationNeuronal inflammationCell populationsReticulum stressPost-ischemic stroke systemic inflammation: Immunomodulation by progesterone and vitamin D hormone
Atif F, Yousuf S, Espinosa-Garcia C, Harris W, Stein D. Post-ischemic stroke systemic inflammation: Immunomodulation by progesterone and vitamin D hormone. Neuropharmacology 2020, 181: 108327. PMID: 32950558, DOI: 10.1016/j.neuropharm.2020.108327.Peer-Reviewed Original ResearchConceptsPeripheral immune dysfunctionVitamin D hormoneTransient middle cerebral artery occlusion/reperfusionImmune dysfunctionSystemic inflammationInfarct volumeSubsets of immune cellsNeuronal inflammationMeasure infarct volumePost-stroke infectionsInjection of lipopolysaccharideIn-hospital infectionStandard of careFlow cytometric analysisMiddle cerebral artery occlusion/reperfusionCleaved caspase-3Combination therapyInflammation groupImmune cellsAdult ratsIncreased morbidityD hormoneBrain post-strokeImmunomodulatory effectsCombined treatmentSex differences in the performance of cognitive tasks in a murine model of metabolic syndrome
Espinosa‐García C, Fuentes‐Venado C, Guerra‐Araiza C, Segura‐Uribe J, Chávez‐Gutiérrez E, Farfán‐García E, Cruz N, Pinto‐Almazán R. Sex differences in the performance of cognitive tasks in a murine model of metabolic syndrome. European Journal Of Neuroscience 2020, 52: 2724-2736. PMID: 32302458, DOI: 10.1111/ejn.14751.Peer-Reviewed Original ResearchConceptsCognitive impairmentSpatial learningLong-term memory impairmentPerformance of cognitive tasksFemale ratsLong-term memoryAssess cognitive impairmentSprague-Dawley maleMetabolic syndromeHypercaloric dietMemory impairmentSpatial memoryCognitive tasksCognitive differencesSex differencesCA1 regionCountless reportsMetS animal modelMale ratsModel of metabolic syndromeControl groupImpairmentMurine model of metabolic syndromeStandard chow dietMemoryProgesterone Attenuates Stress-Induced NLRP3 Inflammasome Activation and Enhances Autophagy Following Ischemic Brain Injury
Espinosa-Garcia C, Atif F, Yousuf S, Sayeed I, Neigh G, Stein D. Progesterone Attenuates Stress-Induced NLRP3 Inflammasome Activation and Enhances Autophagy Following Ischemic Brain Injury. International Journal Of Molecular Sciences 2020, 21: 3740. PMID: 32466385, PMCID: PMC7312827, DOI: 10.3390/ijms21113740.Peer-Reviewed Original ResearchConceptsHigh-mobility group box 1HMGB1 releaseIschemic brain injuryNLRP3 inflammasome activationExposed to social defeat stressGlobal ischemiaIschemic animalsAssociated with cardiac arrestInflammasome activationAdult male Sprague-Dawley ratsMale Sprague-Dawley ratsNeonatal brain tissueHippocampus of ischemic animalsRodent models of cerebral ischemiaSocial defeat stressRelease of alarminsModels of cerebral ischemiaSprague-Dawley ratsBrain injuryNOD-like receptor pyrin domainNLRP3 inflammasomeResponse to ischemiaPrimed with lipopolysaccharideBlocks progesteroneDays post-ischemia
2013
Effects of progesterone on neurite growth inhibitors in the hippocampus following global cerebral ischemia
Espinosa-García C, Aguilar-Hernández A, Cervantes M, Moralí G. Effects of progesterone on neurite growth inhibitors in the hippocampus following global cerebral ischemia. Brain Research 2013, 1545: 23-34. PMID: 24316245, DOI: 10.1016/j.brainres.2013.11.030.Peer-Reviewed Original ResearchConceptsEffects of progesteroneGlobal cerebral ischemiaMorris water mazeCA1 pyramidal neuronsNogo-ACerebral ischemiaPyramidal neuronsRho ACell bodies of CA1 pyramidal neuronsNeurite growth inhibitor Nogo-ASpatial learningVehicle-treated ratsAdult male ratsTreated with P4Effects of P4Dendritic arborization of CA1 pyramidal neuronsAssociated with parametersNeurite growth inhibitorsFunction preservationMale ratsRat hippocampusWater mazeIschemiaHippocampal layersRatsPost-ischemic administration of progesterone reduces caspase-3 activation and DNA fragmentation in the hippocampus following global cerebral ischemia
Espinosa-García C, Vigueras-Villaseñor R, Rojas-Castañeda J, Aguilar-Hernández A, Monfil T, Cervantes M, Moralí G. Post-ischemic administration of progesterone reduces caspase-3 activation and DNA fragmentation in the hippocampus following global cerebral ischemia. Neuroscience Letters 2013, 550: 98-103. PMID: 23810799, DOI: 10.1016/j.neulet.2013.06.023.Peer-Reviewed Original ResearchConceptsCaspase-3 levelsGlobal cerebral ischemia/reperfusionCaspase-3Pyramidal neuronsCaspase-3 activityAdult male Sprague-Dawley ratsHippocampal CA1 pyramidal neuronsNeuroprotective effects of progesteroneCerebral ischemia/reperfusionMale Sprague-Dawley ratsGlobal cerebral ischemia/reperfusion injuryCA1 pyramidal neuronsNeuroprotective effectsEffects of progesteroneAdministration of progesteroneIschemia/reperfusion-induced increasesSprague-Dawley ratsFour-vessel occlusion modelModels of brain injuryEffects of P4CA1 neuronal lossGlobal cerebral ischemiaPost-ischemic administrationCerebral ischemia/reperfusion injuryDNA fragmentation
2011
Neuroprotective effects of progesterone and allopregnanolone on long-term cognitive outcome after global cerebral ischemia.
Moralí G, Montes P, Hernández-Morales L, Monfil T, Espinosa-García C, Cervantes M. Neuroprotective effects of progesterone and allopregnanolone on long-term cognitive outcome after global cerebral ischemia. Restorative Neurology And Neuroscience 2011, 29: 1-15. PMID: 21335664, DOI: 10.3233/rnn-2011-0571.Peer-Reviewed Original ResearchConceptsNeuroprotective effects of progesteroneEffects of progesteroneTreated ratsGlobal cerebral ischemiaLoss of hippocampal pyramidal neuronsPyramidal neuronsLong-term cognitive outcomesCerebral ischemiaAdult male Sprague-Dawley ratsMale Sprague-Dawley ratsLoss of pyramidal neuronsHippocampal pyramidal neuronsSprague-Dawley ratsWorking memoryMemory testTreated with P4Spatial learningCognitive outcomesAllopregnanoloneNeural conditionsIntact ratsHippocampusSham procedureForebrain ischemiaNonischemic controls