Journal article
Hyperacute immune responses associate with immediate neuropathology and motor dysfunction in large vessel occlusions
Annals of clinical and translational neurology, Vol.10(2), pp.276-291
02/2023
DOI: 10.1002/acn3.51719
PMCID: PMC9930422
PMID: 36579400
Abstract
Objective
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-γ and MMP-9, while GM-CSF, IL-17, TNF-α, 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.
Details
- Title: Subtitle
- Hyperacute immune responses associate with immediate neuropathology and motor dysfunction in large vessel occlusions
- Creators
- Mudassir Farooqui - Department of Neurology University of Iowa Iowa City Iowa USASantiago Ortega‐Gutierrez - Department of Neurology University of Iowa Iowa City Iowa USA, Department of Neurosurgery, and Radiology University of Iowa Iowa City Iowa USAKatherine Hernandez - Department of Microbiology, Immunology, and Genetics University of North Texas Health Science Center Fort Worth Texas USAVanessa O. Torres - The University of Texas Southwestern Medical CenterAndres Dajles - University of IowaCynthia B. Zevallos - University of IowaDarko Quispe‐Orozco - Department of Neurology University of Iowa Iowa City Iowa USAAlan Mendez‐Ruiz - Department of Neurology University of Iowa Iowa City Iowa USAKenneth Manzel - University of IowaPatrick Ten Eyck - University of IowaDaniel Tranel - University of IowaNitin J. Karandikar - University of IowaSterling B. Ortega - Department of Microbiology, Immunology, and Genetics University of North Texas Health Science Center Fort Worth Texas USA, Department of Pathology University of Iowa Iowa City Iowa USA
- Resource Type
- Journal article
- Publication Details
- Annals of clinical and translational neurology, Vol.10(2), pp.276-291
- DOI
- 10.1002/acn3.51719
- PMID
- 36579400
- PMCID
- PMC9930422
- ISSN
- 2328-9503
- eISSN
- 2328-9503
- Grant note
- DOI: 10.13039/100015515, name: Roy J. and Lucille A. Carver College of Medicine, University of Iowa; DOI: 10.13039/100011343, name: Holden Comprehensive Cancer Center, University of Iowa; DOI: 10.13039/100006441, name: Center for Outcomes Research and Evaluation, Yale School of Medicine, award: UL1TR002537; DOI: 10.13039/100007930, name: Institute of Clinical and Translational Sciences; DOI: 10.13039/100000002, name: National Institutes of Health, award: R01AI121567; DOI: 10.13039/100000054, name: National Cancer Institute; DOI: 10.13039/100000060, name: National Institute of Allergy and Infectious Diseases, award: P30CA086862
- Language
- English
- Electronic publication date
- 12/28/2022
- Date published
- 02/2023
- Academic Unit
- Neurology; Radiology; Psychological and Brain Sciences; Pathology; Iowa Neuroscience Institute; Biostatistics; Neurosurgery
- Record Identifier
- 9984354511802771
Metrics
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