Evidence map›Paper›PMID 41354124›Full record

ArticleNeuropharmacology2026

Evaluating tocilizumab in ischemic stroke: Findings from the SPAN multicenter trial.

Anjali Chauhan, Eunyoung Angela Lee, Rakesh B Patel, Mariia Kumskova, Enrique C Leira, Anil K Chauhan, Yanrong Shi, Suyi Cao, Raymond C Koehler, Krishnan M Dhandapani and 18 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuropharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors.

Anjali ChauhanDepartment of Neurology, McGovern Medical School, University of Texas HSC, Houston, TX, USA.
Eunyoung Angela LeeDepartment of Neurology, McGovern Medical School, University of Texas HSC, Houston, TX, USA.
Rakesh B PatelDepartment of Internal Medicine, University of Iowa, Iowa City, IA, USA.
Mariia KumskovaDepartment of Internal Medicine, University of Iowa, Iowa City, IA, USA.
Enrique C LeiraDepartment of Internal Medicine, University of Iowa, Iowa City, IA, USA.
Anil K ChauhanDepartments of Neurology, Neurosurgery, and Epidemiology, University of Iowa, Iowa City, IA, USA.
Yanrong ShiDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Suyi CaoDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Raymond C KoehlerDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Krishnan M DhandapaniDepartment of Neurosurgery, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Mohammad Badruzzaman KhanDepartment of Neurosurgery, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Pradip K KamatDepartment of Neurosurgery, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Ali ArbabDepartment of Neurosurgery, Medical College of Georgia, Augusta University, Augusta, GA, USA.
David C HessDepartment of Neurosurgery, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Alison L HermanDepartment of Neurology, Yale University School of Medicine, New Haven, CT, USA.
Ligia BoisserandDepartment of Neurology, Yale University School of Medicine, New Haven, CT, USA.
Lauren H SansingDepartment of Neurology, Yale University School of Medicine, New Haven, CT, USA.
Andreia MoraisDepartment of Neurology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, 02114, USA.
Xuyan JinDepartment of Neurology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, 02114, USA.
Sanem AykanDepartment of Neurology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, 02114, USA.
Takahiko ImaiDepartment of Neurology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, 02114, USA.
Cenk AyataDepartment of Neurology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, 02114, USA.
Karisma A NagarkattiDepartment of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine at USC, Los Angeles, CA, USA.
Jessica LambDepartment of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine at USC, Los Angeles, CA, USA.
Márcio A DinizDepartment of Population Health Science and Policy, Icahn School of Medicine, Mount Sinai, NY, NY, USA.
Patrick D LydenDepartment of Physiology and Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine at USC, Los Angeles, CA, USA; Department of Neurology, Keck School of Medicine at USC, Los Angeles, CA, USA.
Louise D McCulloughDepartment of Neurology, McGovern Medical School, University of Texas HSC, Houston, TX, USA.
Jaroslaw AronowskiDepartment of Neurology, McGovern Medical School, University of Texas HSC, Houston, TX, USA. Electronic address: J.Aronowski@uth.tmc.edu.

Funding

TR&D3: Intrinsic Surface MappingP41EB015922 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI VAN HORN, JOHN DARRELL · 2012 to 2022
$14.1M
Targeting Pyruvate Kinase M2: A novel strategy to combat thrombo-inflammationR35HL139926 · NHLBI · UNIVERSITY OF IOWA · PI CHAUHAN, ANIL KUMAR · 2018 to 2024
$5.3M
Sex Differences in Inflammation Across the LifespanR35NS132265 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Louise D. McCullough · 2023 to 2026
$4.5M
The NIH SPAN Coordinating CenterU24NS113452 · NINDS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI LYDEN, PATRICK D · 2019 to 2021
$2.4M
Wnt Signaling in StrokeR01NS105894 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KOEHLER, RAYMOND CHARLES · 2018 to 2022
$2.3M
Microglia/macrophage polarization after intracerebral hemorrhageR01NS102583 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KOEHLER, RAYMOND CHARLES · 2018 to 2021
$1.8M
Targeting RBC dysfunction in VCIDRF1NS122863 · NINDS · AUGUSTA UNIVERSITY · PI HESS, DAVID C. · 2021 to 2021
$1.6M
Mechanisms of Chronic Remote Ischemic Conditioning Induced Cerebroprotection in a VCID ModelR01NS099455 · NINDS · AUGUSTA UNIVERSITY · PI HESS, DAVID C. · 2017 to 2020
$1.5M
Yale site for Stroke Preclinical Assessment Network (SPAN) for Acute NeuroprotectionU01NS113445 · NINDS · YALE UNIVERSITY · PI SANSING, LAUREN H · 2019 to 2021
$1.2M
Multicenter preclinical trial of rho-kinase inhibitor fasudil in acute focal cerebral ischemia and reperfusionU01NS113443 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI AYATA, CENK · 2019 to 2021
$1.2M
Stroke Preclinical Assessment Network (SPAN) – Tacilizumab for treatment of acute ischemic strokeU01NS113451 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI ARONOWSKI, JAROSLAW · 2019 to 2021
$1.1M
The University of Iowa Stroke Preclinical Assessment Center for Neuroprotection in strokeU01NS113388 · NINDS · UNIVERSITY OF IOWA · PI CHAUHAN, ANIL KUMAR, LEIRA, ENRIQUE CARLOS · 2019 to 2021
$1.1M
NHLBI NIH HHS R35 HL139926NIBIB NIH HHS P41 EB015922NINDS NIH HHS R01 NS099455NINDS NIH HHS R01 NS102583NINDS NIH HHS R01 NS105894NINDS NIH HHS R35 NS132265NINDS NIH HHS RF1 NS122863NINDS NIH HHS U01 NS113356NINDS NIH HHS U01 NS113388NINDS NIH HHS U01 NS113443NINDS NIH HHS U01 NS113444NINDS NIH HHS U01 NS113445NINDS NIH HHS U01 NS113451NINDS NIH HHS U24 NS113452
6 · The paper itself

Abstract

Inflammation, particularly mediated through interleukin-6 (IL-6) signaling, plays a critical role in stroke pathophysiology. High levels of IL-6 are associated with poor outcomes in stroke patients. Therapeutic inhibition of IL-6 signaling may offer a novel strategy to mitigate post-stroke damage and improve recovery. This study evaluated the efficacy of tocilizumab (TCZ), a clinically approved monoclonal antibody that blocks IL-6 receptor signaling, using data from the Stroke Preclinical Assessment Network (SPAN), a multi-center, randomized, blinded, placebo-controlled trial in preclinical stroke models.

methodsWe analyzed behavioral and MRI morphometry data from 701 rodents (both males and females; 1:1), including healthy young mice, diet-induced obese mice, aging mice, and spontaneously hypertensive rats (SHR) treated with saline (N = 348) or TCZ (N = 353) at a dose of 100 mg/kg for mice, 10 mg/kg for rats after middle cerebral artery occlusion (MCAO).

resultsIn the overall mouse cohort, TCZ did not significantly improve long-term sensorimotor recovery or reduce brain tissue loss measured by MRI. However, aging mice exhibited modest motor function improvements. In SHRs, TCZ treatment resulted in improved sensory-motor function, particularly in male rats, as demonstrated by enhanced corner test scores on days 7 and 28 post-MCAO. While TCZ in SHRs provided early (day 2) cerebroprotection with reduced lesion volume, it did not alter subsequent tissue loss, as measured by tissue atrophy at day 30.

conclusionsThese results suggest that IL-6R blockade with TCZ was associated with functional improvement in aging mice (modest) and hypertensive rats (notably males), without durable effect of brain tissue loss. No benefit was observed in the overall mouse cohort. These findings support IL-6 signaling as a viable therapeutic target and warrant further investigation into IL-6 receptor inhibition as a potential treatment strategy for stroke recovery.

Indexed as

Antibodies, Monoclonal, HumanizedIschemic StrokeAnimalsBrainDisease Models, AnimalFemaleInfarction, Middle Cerebral ArteryMagnetic Resonance ImagingMaleMiceMice, Inbred C57BLRatsRats, Inbred SHRReceptors, Interleukin-6Antibodies, Monoclonal, HumanizedReceptors, Interleukin-6tocilizumabIL-6R inhibitorIschemic strokePreclinical stroke modelsSPANTocilizumab

Identifiers

PMID41354124
PMCPMC13543173

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.