Journal article
Evaluating Tocilizumab in Ischemic Stroke: Findings from the SPAN Multicenter Trial
Neuropharmacology, Vol.285, 110801
03/01/2026
DOI: 10.1016/j.neuropharm.2025.110801
PMCID: PMC13543173
PMID: 41354124
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.
We 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).
: In 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.
These 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.
•Preclinical SPAN platform: TCZ vs saline in 701 animals across young, aging, and comorbid models.•Mice: no overall benefit; aging mice showed modest motor gains without neuroprotection.•SHRs: improved corner test scores (D7/D28) and smaller early lesions; recovery without tissue preservation.
Details
- Title: Subtitle
- Evaluating Tocilizumab in Ischemic Stroke: Findings from the SPAN Multicenter Trial
- Creators
- Anjali Chauhan - The University of Texas Health Science Center at HoustonEunyoung Angela Lee - The University of Texas Health Science Center at HoustonRakesh B. Patel - University of IowaMariia Kumskova - University of IowaEnrique C. Leira - University of IowaAnil K. Chauhan - University of IowaYanrong Shi - Johns Hopkins UniversitySuyi Cao - Johns Hopkins UniversityRaymond C. Koehler - Johns Hopkins UniversityKrishnan M. Dhandapani - Augusta UniversityMohammad Badruzzaman Khan - Augusta UniversityPradip K. Kamat - Augusta UniversityAli Arbab - Augusta UniversityDavid C. Hess - Augusta UniversityAlison L. Herman - Yale UniversityLigia Boisserand - Yale UniversityLauren H. Sansing - Yale UniversityAndreia Morais - Massachusetts General HospitalXuyan Jin - Massachusetts General HospitalSanem Aykan - Harvard UniversityTakahiko Imai - Harvard UniversityCenk Ayata - Harvard UniversityKarisma A. Nagarkatti - University of Southern CaliforniaJessica Lamb - University of Southern CaliforniaMárcio A. Diniz - Icahn School of Medicine at Mount SinaiPatrick D. Lyden - University of Southern CaliforniaLouise D. McCullough - University of Southern CaliforniaJaroslaw Aronowski - The University of Texas Health Science Center at Houston
- Resource Type
- Journal article
- Publication Details
- Neuropharmacology, Vol.285, 110801
- DOI
- 10.1016/j.neuropharm.2025.110801
- PMID
- 41354124
- PMCID
- PMC13543173
- NLM abbreviation
- Neuropharmacology
- ISSN
- 0028-3908
- eISSN
- 1873-7064
- Publisher
- Elsevier Ltd
- Grant note
- University: R01 NS099455, RF1NS122863, U01NS113356 Laboratory of Neuro Imaging Resource (LONIR) at the University of Southern California: P41EB015922
National Institutes of Health Funding to Massachusetts General Hospital (U01NS113443, C. Ayata) , Yale University (U01NS113445, L. H. Sansing) , University of Texas (U01NS113451, J. Aronowski, R35NS132265, L.D. McCullough) , the University of Southern California (U24NS113452, P.D. Lyden) , Johns Hopkins University (U01NS113444, R01NS102583, and R01NS105894) , University of Iowa (U01NS113388, A.K. Chauhan and E.C. Leira; R35HL139926, A.K. Chauhan) , Augusta University (R01 NS099455; RF1NS122863 and U01NS113356, D.C. Hess) , and The Laboratory of Neuro Imaging Resource (LONIR) at the University of Southern California (P41EB015922) .r University (R01 NS099455; RF1NS122863 and U01NS113356, D.C. Hess) , and The Laboratory of Neuro Imaging Resource (LONIR) at the University of Southern California (P41EB015922) .
- Language
- English
- Date published
- 03/01/2026
- Academic Unit
- Neurology; Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Iowa Neuroscience Institute; Neurosurgery; Internal Medicine
- Record Identifier
- 9985091809102771
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