2024
VEGF-C prophylaxis favors lymphatic drainage and modulates neuroinflammation in a stroke model
Boisserand L, Geraldo L, Bouchart J, Kamouh M, Lee S, Sanganahalli B, Spajer M, Zhang S, Lee S, Parent M, Xue Y, Skarica M, Yin X, Guegan J, Boyé K, Leser F, Jacob L, Poulet M, Li M, Liu X, Velazquez S, Singhabahu R, Robinson M, Askenase M, Osherov A, Sestan N, Zhou J, Alitalo K, Song E, Eichmann A, Sansing L, Benveniste H, Hyder F, Thomas J. VEGF-C prophylaxis favors lymphatic drainage and modulates neuroinflammation in a stroke model. Journal Of Experimental Medicine 2024, 221: e20221983. PMID: 38442272, PMCID: PMC10913814, DOI: 10.1084/jem.20221983.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factor-CDeep cervical lymph nodesCentral nervous systemEffect of vascular endothelial growth factor-CMeningeal lymphatic vesselsAmeliorated motor performanceCervical lymph nodesIschemic strokeVEGF-C overexpressionIncreased BDNF signalingAcute ischemic strokeBrain cellsIncreased CSF drainageIschemic stroke outcomesModel of ischemic strokeMouse model of ischemic strokeImmune surveillanceCSF drainageLymph nodesFluid drainageNucleus RNA sequencingLymphatic growthLymphatic drainageMouse modelBDNF signaling
2023
Fluorescent liposomal nanocarriers for targeted drug delivery in ischemic stroke therapy
Arul M, Alahmadi I, Turro D, Ruikar A, Abdulmalik S, Williams J, Sanganahalli B, Liang B, Verma R, Kumbar S. Fluorescent liposomal nanocarriers for targeted drug delivery in ischemic stroke therapy. Biomaterials Science 2023, 11: 7856-7866. PMID: 37902365, PMCID: PMC10697427, DOI: 10.1039/d3bm00951c.Peer-Reviewed Original ResearchConceptsSurgical clot removalPEGylated liposomal formulationPreclinical mouse modelsShorter treatment durationPurinergic receptor P2X4Reduced infarct volumeAcute CNS injuryCNS infiltrationLong-term disabilitySystemic deliveryTreatment optionsLiposomal formulationIschemic stroke therapyVulnerable brain regionsAdministered 4Clot removalInfarct volumeLow dosesTreatment durationMouse modelNeuroprotective therapiesCNS injuryLiposomal nanocarriersStroke therapyIschemic strokeA multi-laboratory preclinical trial in rodents to assess treatment candidates for acute ischemic stroke
Lyden P, Diniz M, Bosetti F, Lamb J, Nagarkatti K, Rogatko A, Kim S, Cabeen R, Koenig J, Akhter K, Arbab A, Avery B, Beatty H, Bibic A, Cao S, Simoes Braga Boisserand L, Chamorro A, Chauhan A, Diaz-Perez S, Dhandapani K, Dhanesha N, Goh A, Herman A, Hyder F, Imai T, Johnson C, Khan M, Kamat P, Karuppagounder S, Kumskova M, Mihailovic J, Mandeville J, Morais A, Patel R, Sanganahalli B, Smith C, Shi Y, Sutariya B, Thedens D, Qin T, Velazquez S, Aronowski J, Ayata C, Chauhan A, Leira E, Hess D, Koehler R, McCullough L, Sansing L. A multi-laboratory preclinical trial in rodents to assess treatment candidates for acute ischemic stroke. Science Translational Medicine 2023, 15: eadg8656. PMID: 37729432, DOI: 10.1126/scitranslmed.adg8656.Peer-Reviewed Original ResearchConceptsPreclinical assessmentFocal cerebral ischemic insultAcute ischemic strokeCerebral ischemic insultLarge clinical trialsDiet-induced obesityNew clinical interventionsIntravascular thrombectomyIschemic strokeStroke treatmentHypertensive ratsIschemic insultBlinded assessmentClinical trialsYoung miceTreatment candidatesExclusion criteriaAnimal modelsYoung ratsFutile interventionsPreclinical trialsClinical interventionsFutility boundariesMiceDisease areasSpatiotemporal features of neurovascular (un)coupling with stimulus-induced activity and hypercapnia challenge in cerebral cortex and olfactory bulb
James S, Sanggaard S, Akif A, Mishra S, Sanganahalli B, Blumenfeld H, Verhagen J, Hyder F, Herman P. Spatiotemporal features of neurovascular (un)coupling with stimulus-induced activity and hypercapnia challenge in cerebral cortex and olfactory bulb. Cerebrovascular And Brain Metabolism Reviews 2023, 43: 1891-1904. PMID: 37340791, PMCID: PMC10676132, DOI: 10.1177/0271678x231183887.Peer-Reviewed Original ResearchConceptsVasodilatory responseCerebral cortexNeurovascular couplingOlfactory bulbNeuronal activityBrief sensory stimuliRegional neurovascular couplingStimulus-induced activityHypercapnia challengeVascular toneNeuronal deactivationHemodynamic responseNeuronal excitabilityNeuronal responsesCalcium transientsBrain functionHemodynamic signalsSensory stimuliVasodilationHypercapniaCortexMiceCareful appraisalStimuliMetabolic wasteConcerted roles of LRRTM1 and SynCAM 1 in organizing prefrontal cortex synapses and cognitive functions
de Arce K, Ribic A, Chowdhury D, Watters K, Thompson G, Sanganahalli B, Lippard E, Rohlmann A, Strittmatter S, Missler M, Hyder F, Biederer T. Concerted roles of LRRTM1 and SynCAM 1 in organizing prefrontal cortex synapses and cognitive functions. Nature Communications 2023, 14: 459. PMID: 36709330, PMCID: PMC9884278, DOI: 10.1038/s41467-023-36042-w.Peer-Reviewed Original ResearchConceptsPrefrontal cortexDKO miceSynCAM 1Aberrant neuronal activityDendritic spine numberPrefrontal cortex synapsesSynapse organizersSynapse numberMature brainNeuronal activityKnockout miceSpine numberSynapse developmentCognitive functionTrans-synaptic complexesImmunoglobulin family membersMiceFamily membersSynapsesLRRTM1Behavioral domainsHippocampusCognitive tasksConcerted roleCortexEmbracing Heterogeneity in The Multicenter Stroke Preclinical Assessment Network (SPAN) Trial
Morais A, Locascio J, Sansing L, Lamb J, Nagarkatti K, Imai T, van Leyen K, Aronowski J, Koenig J, Bosetti F, Lyden P, Ayata C, Bosetti F, Koenig J, Lyden P, Lamb J, Nagarkatti K, Hess D, Kamat P, Khan M, Dhandapani K, Arbab A, Siddiqui S, Smith C, Nisar M, Leira E, Chauhan A, Dhanesha N, Patel R, Kumskova M, Thedens D, Wang K, Ayata C, Morais A, Imai T, Qin T, Jin X, Erdogan T, Yu L, Mandeville J, Kimberly W, Whittier J, Lo E, Arai K, Van Leyen K, Sansing L, Hyder F, Mihailovic J, Sanganahalli B, Diaz-Perez S, Velazquez S, Beatty H, Johnson C, Herman A, Boisserand L, Immakavar E, Koehler R, Dawson T, Dawson V, Shi Y, Avery B, Lannon S, Bibic A, Akhter K, Karuppagounder S, Aronowski J, McCullough L, Obertas L, Goh A, Huang S, Chauhan A. Embracing Heterogeneity in The Multicenter Stroke Preclinical Assessment Network (SPAN) Trial. Stroke 2023, 54: 620-631. PMID: 36601951, PMCID: PMC9870939, DOI: 10.1161/strokeaha.122.040638.Peer-Reviewed Original ResearchConceptsTotal anesthesia durationAnesthesia durationIndependent predictorsMultivariable analysisClinical trialsTransient focal cerebral ischemiaFocal cerebral ischemiaCerebral blood flowLaser Doppler flowCentralized randomizationModified intentionTreat populationExperimental strokeCerebral ischemiaDoppler flowRodent modelsMCAOBlood flowNetwork trialFlow dropPreclinical trialsMouse cohortsStudy designTrialsTrial onset
2022
The Stroke Preclinical Assessment Network: Rationale, Design, Feasibility, and Stage 1 Results
Lyden PD, Bosetti F, Diniz MA, Rogatko A, Koenig JI, Lamb J, Nagarkatti KA, Cabeen RP, Hess DC, Kamat PK, Khan MB, Wood K, Dhandapani K, Arbab AS, Leira EC, Chauhan AK, Dhanesha N, Patel RB, Kumskova M, Thedens D, Morais A, Imai T, Qin T, Ayata C, Boisserand LSB, Herman AL, Beatty HE, Velazquez SE, Diaz-Perez S, Sanganahalli BG, Mihailovic JM, Hyder F, Sansing LH, Koehler RC, Lannon S, Shi Y, Karuppagounder SS, Bibic A, Akhter K, Aronowski J, McCullough LD, Chauhan A, Goh A, Siddiqui S, Sheth K, Matouk C, Cruz C, Zhou J, Dawson V, Dawson T, Liang J, van Zijl P, Zeiler S, Taylor Kimberly W, Erdogan T, Yu L, Mandeville J, Whittier J. The Stroke Preclinical Assessment Network: Rationale, Design, Feasibility, and Stage 1 Results. Stroke 2022, 53: 1802-1812. PMID: 35354299, PMCID: PMC9038686, DOI: 10.1161/strokeaha.121.038047.Peer-Reviewed Original ResearchConceptsPreclinical assessmentStroke treatmentCandidate treatmentMiddle cerebral artery occlusion (MCAO) surgeryClinical stroke trialsSuccessful stroke treatmentInclusion/exclusion criteriaStroke clinical trialsClinical trial designYoung male animalsComorbid diseasesOcclusion surgeryCerebral ischemiaNeurological disabilityComorbid conditionsStroke trialsProtocol adherenceBlinded assessmentSuch therapyClinical trialsClinical studiesExclusion criteriaTrial designAged animalsOutcome assessment
2021
Small loci of astroglial glutamine synthetase deficiency in the postnatal brain cause epileptic seizures and impaired functional connectivity
Farina MG, Sandhu MRS, Parent M, Sanganahalli BG, Derbin M, Dhaher R, Wang H, Zaveri HP, Zhou Y, Danbolt NC, Hyder F, Eid T. Small loci of astroglial glutamine synthetase deficiency in the postnatal brain cause epileptic seizures and impaired functional connectivity. Epilepsia 2021, 62: 2858-2870. PMID: 34536233, PMCID: PMC9006438, DOI: 10.1111/epi.17072.Peer-Reviewed Original ResearchConceptsPostnatal brainFunctional connectivityContinuous video-electroencephalographic recordingSpontaneous recurrent seizuresPathogenesis of epilepsyGlutamine synthetase deficiencyVideo-electroencephalographic recordingsSpecific animal modelsEx vivo studySeizure thresholdAdult patientsRecurrent seizuresFocal epilepsyAdeno-associated virusHippocampal formationAnimal modelsFocal mannerEpileptic seizuresGS deficiencySmall lociSynthetase deficiencyEpilepsyGradual returnVivo studiesBrain
2020
APOE genotype-dependent pharmacogenetic responses to rapamycin for preventing Alzheimer's disease
Lin AL, Parikh I, Yanckello LM, White RS, Hartz AMS, Taylor CE, McCulloch SD, Thalman SW, Xia M, McCarty K, Ubele M, Head E, Hyder F, Sanganahalli BG. APOE genotype-dependent pharmacogenetic responses to rapamycin for preventing Alzheimer's disease. Neurobiology Of Disease 2020, 139: 104834. PMID: 32173556, PMCID: PMC7486698, DOI: 10.1016/j.nbd.2020.104834.Peer-Reviewed Original ResearchConceptsCerebral blood flowAsymptomatic APOE4 carriersE4FAD miceAPOE4 carriersAlzheimer's diseaseCerebrovascular reactivityNeurotransmitter levelsE3FAD micePharmacogenetic responsePharmacogenetic differencesSomatosensory responsesBlood-brain barrier functionBrain functionStrongest genetic risk factorBrain metabolic changesFree fatty acid levelsAmyloid-beta plaquesHuman APOE4 geneDifferent APOE allelesAPOE ε3 alleleFuture clinical testingGenetic risk factorsFatty acid levelsWhite matter integrityAβ transport
2016
Afatinib plus Cetuximab Delays Resistance Compared to Single-Agent Erlotinib or Afatinib in Mouse Models of TKI-Naïve EGFR L858R-Induced Lung Adenocarcinoma
Pirazzoli V, Ayeni D, Meador CB, Sanganahalli BG, Hyder F, de Stanchina E, Goldberg SB, Pao W, Politi K. Afatinib plus Cetuximab Delays Resistance Compared to Single-Agent Erlotinib or Afatinib in Mouse Models of TKI-Naïve EGFR L858R-Induced Lung Adenocarcinoma. Clinical Cancer Research 2016, 22: 426-435. PMID: 26341921, PMCID: PMC4715986, DOI: 10.1158/1078-0432.ccr-15-0620.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAfatinibAnimalsCell Line, TumorCetuximabDrug Evaluation, PreclinicalDrug Resistance, NeoplasmDrug Therapy, CombinationErbB ReceptorsErlotinib HydrochlorideLung NeoplasmsMiceMice, NudeMutationNeoplasm Recurrence, LocalProtein Kinase InhibitorsProtein-Tyrosine KinasesProto-Oncogene Proteins p21(ras)QuinazolinesConceptsTyrosine kinase inhibitorsLung adenocarcinomaLung cancerMouse modelAdvanced EGFR-mutant lung adenocarcinomaFirst-generation tyrosine kinase inhibitorSingle-agent tyrosine kinase inhibitorsEGFR-mutant lung cancerEGFR-mutant lung adenocarcinomaEGFR tyrosine kinase inhibitorsCetuximab-resistant tumorsPotential of afatinibFirst-line therapyMutant lung cancerEGFR antibody cetuximabCombination of afatinibEGFR-TKI afatinibClinical trial developmentEffective treatment strategiesDrug-resistant tumorsAgent erlotinibTKI-naïveAfatinib treatmentTumor escapeClinical trials