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 areasEmbracing 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