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
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 ResearchMeSH KeywordsAnimalsCell Line, TumorEnergy MetabolismGlioblastomaHumansMitochondriaOxygen ConsumptionProgesteroneSmegmamorphaConceptsExtracellular 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
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 treatmentProgesterone 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
2017
Goldstein et al.'s Secondary Analysis of Progesterone Clinical Trial for Traumatic Brain Injury Can Only Reflect the Same Trial Design Flaws: A Response to “Very Early Administration of Progesterone Does Not Improve Neuropsychological Outcomes in Subjects with Moderate to Severe Traumatic Brain Injury”
Stein D, Sayeed I, Espinosa-Garcia C, Atif F, Sergeeva E. Goldstein et al.'s Secondary Analysis of Progesterone Clinical Trial for Traumatic Brain Injury Can Only Reflect the Same Trial Design Flaws: A Response to “Very Early Administration of Progesterone Does Not Improve Neuropsychological Outcomes in Subjects with Moderate to Severe Traumatic Brain Injury”. Journal Of Neurotrauma 2017, 34: 2192-2193. PMID: 28088875, DOI: 10.1089/neu.2016.4949.Peer-Reviewed Original Research
2016
On the Limitations of Progesterone Treatment in Very Severe Traumatic Brain Injury: What Can Be Learned from Allitt et al., “Progesterone Exacerbates Short-Term Effects of Traumatic Brain Injury”
Atif F, Espinosa-Garcia C, Sayeed I, Sergeeva E, Turan N, Wali B, Wright D, Yousuf S, Stein D. On the Limitations of Progesterone Treatment in Very Severe Traumatic Brain Injury: What Can Be Learned from Allitt et al., “Progesterone Exacerbates Short-Term Effects of Traumatic Brain Injury”. Journal Of Neurotrauma 2016, 34: 1488-1489. PMID: 27138302, DOI: 10.1089/neu.2016.4488.Peer-Reviewed Original Research
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