Featured Publications
Stress primes microglial polarization after global ischemia: Therapeutic potential of progesterone
Espinosa-Garcia C, Sayeed I, Yousuf S, Atif F, Sergeeva E, Neigh G, Stein D. Stress primes microglial polarization after global ischemia: Therapeutic potential of progesterone. Brain Behavior And Immunity 2017, 66: 177-192. PMID: 28648389, DOI: 10.1016/j.bbi.2017.06.012.Peer-Reviewed Original ResearchConceptsAnti-inflammatory cytokinesGlobal ischemiaDays of social defeat stressIncreased pro-inflammatory cytokine expressionPost-ischemiaIntraperitoneal injections of progesteroneNeuroprotective effects of progesteroneMale Sprague-Dawley ratsIschemic strokeAssociated with increased riskMicroglial polarizationSocial defeat stressCA1 hippocampal regionEffects of progesteroneAssociated with increased risk of strokePro-inflammatory cytokine expressionSprague-Dawley ratsNeurotrophic factor expressionInjection of progesteroneAnti-inflammatory mediatorsPro-inflammatory cytokinesExacerbate neuronal lossRisk of strokeM2 phenotype markersPotential therapeutic strategy
2024
Native-state proteomics of Parvalbumin interneurons identifies unique molecular signatures and vulnerabilities to early Alzheimer’s pathology
Kumar P, Goettemoeller A, Espinosa-Garcia C, Tobin B, Tfaily A, Nelson R, Natu A, Dammer E, Santiago J, Malepati S, Cheng L, Xiao H, Duong D, Seyfried N, Wood L, Rowan M, Rangaraju S. Native-state proteomics of Parvalbumin interneurons identifies unique molecular signatures and vulnerabilities to early Alzheimer’s pathology. Nature Communications 2024, 15: 2823. PMID: 38561349, PMCID: PMC10985119, DOI: 10.1038/s41467-024-47028-7.Peer-Reviewed Original ResearchConceptsBiotinylation of proteinsAlzheimer's diseasePre-synaptic defectsDecreased mTOR signalingAD pathogenesisAD riskCytoskeletal disruptionProteomic alterationsTranslational activityMolecular insightsMTOR signalingProteomic findingsProteomicsProteomic signatureMolecular signaturesProteinOver-representedProgressive neuropathologyAlzheimer pathologyMouse modelPV-INsParvalbumin interneuronsMitochondriaAssociated with cognitive declineFast-spiking parvalbumin interneurons
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
2021
Progesterone Modulates Mitochondrial Functions in Human Glioblastoma Cells
Atif F, Yousuf S, Espinosa-Garcia C, Stein D. Progesterone Modulates Mitochondrial Functions in Human Glioblastoma Cells. Molecular Neurobiology 2021, 58: 3805-3816. PMID: 33847913, DOI: 10.1007/s12035-021-02382-1.Peer-Reviewed Original ResearchConceptsExtracellular acidification rateEffects of P4Glioblastoma multiformeGlioblastoma multiforme cell linesGlioblastoma multiforme cellsCell linesInhibitory effectDecreased tumor sizeSuperoxide radical generationMitochondrial functionDose-dependent inhibitory effectOxygen consumption rateTime-response studiesMitochondrial respirationHuman glioblastoma multiformeMitochondrial stress testSpread of glioblastoma multiformeCompared to controlsTumor sizeConcentrations of P4Human glioblastoma cellsModulate mitochondrial functionNonmitochondrial oxygen consumptionMaximum inhibitory effectDose response
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-6Stroke-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
2019
Progesterone Treatment Attenuates Glycolytic Metabolism and Induces Senescence in Glioblastoma
Atif F, Yousuf S, Espinosa-Garcia C, Sergeeva E, Stein D. Progesterone Treatment Attenuates Glycolytic Metabolism and Induces Senescence in Glioblastoma. Scientific Reports 2019, 9: 988. PMID: 30700763, PMCID: PMC6353890, DOI: 10.1038/s41598-018-37399-5.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsApoptosisBehavior, AnimalBiomarkersCell Line, TumorCell ProliferationCell SurvivalCellular SenescenceEnzyme AssaysGlioblastomaGlycolysisLuciferasesMice, NudeModels, BiologicalMotor ActivityNeovascularization, PathologicPhosphatidylinositol 3-KinasesProgesteroneProto-Oncogene Proteins c-aktSignal TransductionTOR Serine-Threonine KinasesConceptsGrowth of glioblastoma multiformeGlycolytic metabolismEffect of progesterone treatmentHigh-dose progesteroneReduced anxiety-like behaviorFollow-up in vitro studyOrthotopic mouse modelSpontaneous locomotor activityAnxiety-like behaviorAthymic nude miceInduce senescenceExpression of GLUT1Increased survival rateCytoplasmic FOXO1Tumor sizeTumor establishmentProgesterone administrationProgesterone treatmentTumor cellsTumor progressionInduce premature senescenceFollow-upNude micePeripheral organsLocomotor activity
2018
Neurosteroid allopregnanolone reduces ipsilateral visual cortex potentiation following unilateral optic nerve injury
Sergeeva E, Espinosa-Garcia C, Atif F, Pardue M, Stein D. Neurosteroid allopregnanolone reduces ipsilateral visual cortex potentiation following unilateral optic nerve injury. Experimental Neurology 2018, 306: 138-148. PMID: 29729249, PMCID: PMC6021019, DOI: 10.1016/j.expneurol.2018.05.005.Peer-Reviewed Original ResearchConceptsOptic nerve crush injuryNeurosteroid allopregnanoloneIntact eyeTherapeutic potential of allopregnanoloneUnilateral optic nerve injuryOptic nerve injuryPost-injury days 3Enhancement of visual responsesSpatial frequency thresholdsNerve crush injuryIpsilateral visual cortexHyper-activityExperience-dependent plasticityVisual cortexModulation of plasticityGABA inhibitionNerve injuryAdult miceSide ipsilateralAllopregnanoloneDay 3Crush injuryCrushed nervesTreated animalsTherapeutic potential
2016
Disruption of motor behavior and injury to the CNS induced by 3-thienylboronic acid in mice
Farfán-García E, Pérez-Rodríguez M, Espinosa-García C, Castillo-Mendieta N, Maldonado-Castro M, Querejeta E, Trujillo-Ferrara J, Soriano-Ursúa M. Disruption of motor behavior and injury to the CNS induced by 3-thienylboronic acid in mice. Toxicology And Applied Pharmacology 2016, 307: 130-137. PMID: 27495897, DOI: 10.1016/j.taap.2016.08.002.Peer-Reviewed Original ResearchConceptsCentral nervous systemDisruption of motor activityDose of 400mg/kgMotor disruptionLoss of neuronsCD1 miceIntraperitoneal administrationMotor behaviorMotor activitySubstantia nigraNervous systemDoseMiceMotor performanceMotor systemCell damageMotor cortexNeurotoxic agentsInjuryBoron-free compoundsEffects of BCCAdministrationScarcity of studies
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