TY - JOUR
T1 - Hyperacute immune responses associate with immediate neuropathology and motor dysfunction in large vessel occlusions
AU - Farooqui, Mudassir
AU - Ortega-Gutierrez, Santiago
AU - Hernandez, Katherine
AU - Torres, Vanessa O.
AU - Dajles, Andres
AU - Zevallos, Cynthia B.
AU - Quispe-Orozco, Darko
AU - Mendez-Ruiz, Alan
AU - Manzel, Kenneth
AU - Ten Eyck, Patrick
AU - Tranel, Daniel
AU - Karandikar, Nitin J.
AU - Ortega, Sterling B.
N1 - Funding Information:
The data presented herein were obtained at the Flow Cytometry Facility, which is a Carver College of Medicine/Holden Comprehensive Cancer Center core research facility at the University of Iowa. The facility is funded through user fees and the generous financial support of the Carver College of Medicine, Holden Comprehensive Cancer Center, and Iowa City Veteran's Administration Medical Center. The authors thank Paul Casella and Kaitlyn Bambino for their helpful discussion and review of the manuscript. Image for Figure IA created with BioRender.
Funding Information:
This work was supported by National Institutes of Health grants R01AI121567 (NIAID, NJK), P30CA086862 (NCI, UI Flow Core), UL1TR002537 (University of Iowa Clinical and Translational Science), and Institute of Clinical and Translational Science Pilot Grant UI StrokeNet, (SBO, and SOG) and Carver College of Medicine (SBO and SOG).
Funding Information:
The data presented herein were obtained at the Flow Cytometry Facility, which is a Carver College of Medicine/Holden Comprehensive Cancer Center core research facility at the University of Iowa. The facility is funded through user fees and the generous financial support of the Carver College of Medicine, Holden Comprehensive Cancer Center, and Iowa City Veteran's Administration Medical Center. The authors thank Paul Casella and Kaitlyn Bambino for their helpful discussion and review of the manuscript. Image for Figure IA created with BioRender.
Publisher Copyright:
© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
PY - 2023/2
Y1 - 2023/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85145328284&partnerID=8YFLogxK
U2 - 10.1002/acn3.51719
DO - 10.1002/acn3.51719
M3 - Article
C2 - 36579400
AN - SCOPUS:85145328284
SN - 2328-9503
VL - 10
SP - 276
EP - 291
JO - Annals of Clinical and Translational Neurology
JF - Annals of Clinical and Translational Neurology
IS - 2
ER -