Neuroinflammatory Factor Response in Acute Ischemic Stroke Correlates with Lesion Volume and Stroke Severity: Circulating Blood from a Mobile Stroke Unit and during Hospitalization
Abstract Body: Background. Circulating neuroinflammatory factors change rapidly in acute stroke, but the association with ischemic lesion size and stroke severity is unknown. We used a mobile stroke unit (MSU) to identify inflammatory markers within minutes of symptom onset, and from blood at 24 hours. We compared these findings with stroke size and severity. Methods. The study is a prospective, cohort investigation of ultra-early blood-derived inflammatory factors in acute stroke. Blood was obtained on the MSU, in the hospital, and from healthy adult controls. Plasma was analyzed with electrochemiluminescence for 9 inflammatory factors. Lesion volume was quantified from MRI with computational software. Variables included demographics and NIHSS. Results. Seventy-one adults were analyzed, including 46 patients treated on the MSU between August 2021 and May 2024, and 25 controls. Twenty-six (57%) MSU patients were confirmed ischemic stroke (AIS). For AIS patients, median age was 65 (range 36-88) years, 42% were female, and 76% white. Median initial NIHSS score was 6 (range 1-22; median hospital discharge NIHSS score was 1 (range 0-20). Twenty-three (88%) patients received IV thrombolysis and 7 (27%) had mechanical thrombectomy. Median lesion volume on MRI was 1.4 (range 0-171) mL. Blood was obtained a median of 57 (range 26-355) minutes from stroke symptom onset on the MSU, and MRI was obtained a median of 12.5 (range 2.2 to 31.8) hours. Compared with controls, of factors evaluated in blood obtained on the MSU, IL-6 and IL-4 were elevated; IFNγ, IL-12p70 and IL-2 were reduced; and IL-10, IL-17, IL-1β and TNF-α were comparable. Plasma levels of IFNγ, IL-17 and IL-2 at 24 hours were inversely correlated with lesion volume (Spearman’s rho: -0.540, -0.558 and -0.423, respectively). Change in IL-17 and IL-2 between the blood obtained on the MSU and blood 24±6 hours later (median +86 fg/mL and +55 fg/mL, respectively) was inversely correlated with lesion volume (Spearman’s rho: -0.580 and -0.495, respectively. Plasma IFNγ in blood on the MSU correlated with NIHSS score at hospital discharge (Spearman’s rho: 0.485). Conclusions. This study found the acute stroke response for circulating inflammatory factors IFNγ, IL-17 and IL-2 correlated with stroke lesion volume and IFNγ correlated with severity on the NIHSS. This suggests these factors may serve as surrogate markers for brain imaging. The findings may aid development of targeted immunomodulatory therapies in acute stroke.
Kowalski, Robert
( University of Colorado
, Aurora
, Colorado
, United States
)
Coughlan, Christina
( University of Colorado
, Aurora
, Colorado
, United States
)
Jones, William
( University of Colorado
, Aurora
, Colorado
, United States
)
Grotta, James
( Memorial Hermann Hospital
, Houston
, Texas
, United States
)
Graner, Michael
( University of Colorado Anschutz
, Aurora
, Colorado
, United States
)
Thompson, John
( University of Colorado
, Parker
, Colorado
, United States
)
Ledreux, Aurelie
( University of Colorado
, Aurora
, Colorado
, United States
)
Violette, John
( Uchealth
, Parker
, Colorado
, United States
)
Paustian, Whitney
( University of Colorado Hospital
, Parker
, Colorado
, United States
)
Neumann, Robert
( University of Colorado
, Aurora
, Colorado
, United States
)
Ornelas, David
( UCHealth
, Morrison
, Colorado
, United States
)
Monte, Andrew
( University of Colorado
, Aurora
, Colorado
, United States
)
Dylla, Layne
( University of Colorado
, Parker
, Colorado
, United States
)
Author Disclosures:
Robert Kowalski:DO have relevant financial relationships
;
Research Funding (PI or named investigator):Bluejay Diagnostics Inc.:Active (exists now)
| Christina Coughlan:No Answer
| William Jones:DO NOT have relevant financial relationships
| James Grotta:DO have relevant financial relationships
;
Consultant:Frazer Ltd:Active (exists now)
; Advisor:Prolong Pharma:Active (exists now)
; Advisor:Acticor:Active (exists now)
; Advisor:Diamedica:Active (exists now)
| Michael Graner:DO NOT have relevant financial relationships
| John Thompson:DO have relevant financial relationships
;
Research Funding (PI or named investigator):Medtronic:Active (exists now)
| Aurelie Ledreux:DO NOT have relevant financial relationships
| John Violette:No Answer
| Whitney Paustian:DO NOT have relevant financial relationships
| Robert Neumann:DO NOT have relevant financial relationships
| David Ornelas:DO NOT have relevant financial relationships
| Andrew Monte:No Answer
| Layne Dylla:DO NOT have relevant financial relationships