Hyperacute immune responses associate with immediate neuropathology and motor dysfunction in large vessel occlusions

dc.creatorFarooqui, Mudassir
dc.creatorOrtega-Gutierrez, Santiago
dc.creatorHernandez, Katherine
dc.creatorTorres, Vanessa O.
dc.creatorDajles, Andres
dc.creatorZevallos, Cynthia B.
dc.creatorQuispe-Orozco, Darko
dc.creatorMendez-Ruiz, Alan
dc.creatorManzel, Kenneth
dc.creatorTen Eyck, Patrick
dc.creatorTranel, Daniel
dc.creatorKarandikar, Nitin J.
dc.creatorOrtega, Sterling B.
dc.creator.orcid0000-0003-3542-9555 (Ortega, Sterling B.)
dc.description.abstractOBJECTIVE: Despite successful endovascular therapy, a proportion of stroke patients exhibit long-term functional decline, regardless of the cortical reperfusion. Our objective was to evaluate the early activation of the adaptive immune response and its impact on neurological recovery in patients with large vessel occlusion (LVO). METHODS: Nineteen (13 females, 6 males) patients with acute LVO were enrolled in a single-arm prospective cohort study. During endovascular therapy (EVT), blood samples were collected from pre and post-occlusion, distal femoral artery, and median cubital vein (controls). Cytokines, chemokines, cellular and functional profiles were evaluated with immediate and follow-up clinical and radiographic parameters, including cognitive performance and functional recovery. RESULTS: In the hyperacute phase (within hours), adaptive immune activation was observed in the post-occlusion intra-arterial environment (post). Ischemic vascular tissue had a significant increase in T-cell-related cytokines, including IFN-gamma and MMP-9, while GM-CSF, IL-17, TNF-alpha, IL-6, MIP-1a, and MIP-1b were decreased. Cellularity analysis revealed an increase in inflammatory IL-17+ and GM-CSF+ helper T-cells, while natural killer (NK), monocytes and B-cells were decreased. A correlation was observed between hypoperfused tissue, infarct volume, inflammatory helper, and cytotoxic T-cells. Moreover, helper and cytotoxic T-cells were also significantly increased in patients with improved motor function at 3 months. INTERPRETATION: We provide evidence of the activation of the inflammatory adaptive immune response during the hyperacute phase and the association of pro-inflammatory cytokines with greater ischemic tissue and worsening recovery after successful reperfusion. Further characterization of these immune pathways is warranted to test selective immunomodulators during the early stages of stroke rehabilitation.
dc.description.sponsorshipThis work was funded by Carver College of Medicine ; Carver College of Medicine/Holden Comprehensive Cancer Center ; Core grant UL1TR002537; Institute of Clinical and Translational Science ; National Institutes of Health grant R01AI121567; NCI ; NIAID grant P30CA086862.
dc.identifier.citationFarooqui, M., Ortega-Gutierrez, S., Hernandez, K., Torres, V. O., Dajles, A., Zevallos, C. B., Quispe-Orozco, D., Mendez-Ruiz, A., Manzel, K., Ten Eyck, P., Tranel, D., Karandikar, N. J., & Ortega, S. B. (2023). Hyperacute immune responses associate with immediate neuropathology and motor dysfunction in large vessel occlusions. Annals of clinical and translational neurology, 10(2), 276-291. https://doi.org/10.1002/acn3.51719
dc.publisherJohn Wiley & Sons, Inc.
dc.rights.holder© 2022 The Authors.
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
dc.sourceAnnals of Clinical and Translational Neurology
dc.subject.meshBrain Ischemia / complications
dc.subject.meshBrain Ischemia / immunology
dc.subject.meshBrain Ischemia / therapy
dc.subject.meshCognitive Dysfunction / etiology
dc.subject.meshCognitive Dysfunction / immunology
dc.subject.meshMotor Skills Disorders / etiology
dc.subject.meshMotor Skills Disorders / immunology
dc.subject.meshDiseases / immunology
dc.subject.meshStroke / complications
dc.subject.meshStroke / immunology
dc.subject.meshStroke / therapy
dc.subject.meshGranulocyte-Macrophage Colony-Stimulating Factor
dc.subject.meshProspective Studies
dc.titleHyperacute immune responses associate with immediate neuropathology and motor dysfunction in large vessel occlusions


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