TY - JOUR
T1 - Evaluating tocilizumab in ischemic stroke
T2 - Findings from the SPAN multicenter trial
AU - Chauhan, Anjali
AU - Lee, Eunyoung Angela
AU - Patel, Rakesh B.
AU - Kumskova, Mariia
AU - Leira, Enrique C.
AU - Chauhan, Anil K.
AU - Shi, Yanrong
AU - Cao, Suyi
AU - Koehler, Raymond C.
AU - Dhandapani, Krishnan M.
AU - Khan, Mohammad Badruzzaman
AU - Kamat, Pradip K.
AU - Arbab, Ali
AU - Hess, David C.
AU - Herman, Alison L.
AU - Boisserand, Ligia
AU - Sansing, Lauren H.
AU - Morais, Andreia
AU - Jin, Xuyan
AU - Aykan, Sanem
AU - Imai, Takahiko
AU - Ayata, Cenk
AU - Nagarkatti, Karisma A.
AU - Lamb, Jessica
AU - Diniz, Márcio A.
AU - Lyden, Patrick D.
AU - McCullough, Louise D.
AU - Aronowski, Jaroslaw
N1 - Publisher Copyright:
© 2025 Elsevier Ltd
PY - 2026/3/1
Y1 - 2026/3/1
N2 - 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. Methods: 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). Results: 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. Conclusions: 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.
AB - 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. Methods: 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). Results: 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. Conclusions: 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.
KW - IL-6R inhibitor
KW - Ischemic stroke
KW - Preclinical stroke models
KW - SPAN
KW - Tocilizumab
UR - https://www.scopus.com/pages/publications/105024468849
UR - https://www.scopus.com/pages/publications/105024468849#tab=citedBy
U2 - 10.1016/j.neuropharm.2025.110801
DO - 10.1016/j.neuropharm.2025.110801
M3 - Article
C2 - 41354124
AN - SCOPUS:105024468849
SN - 0028-3908
VL - 285
JO - Neuropharmacology
JF - Neuropharmacology
M1 - 110801
ER -