SPAN Project

SPAN 2.0

About the project

The Stroke Preclinical Assessment Network (SPAN) is a multi-center multi-stage preclinical study of putative neuroprotectants combined with reperfusion. SPAN utilizes a novel, adaptive, secured system for parallel testing of promising interventions designed to extend the treatment time window and/or improve outcome compared to reperfusion when combined with thrombolysis, thrombectomy or both.

SPAN was established to address a significant need in the scientific investigation of stroke treatment. In the past, a plethora of putative neuroprotectants proceeded to clinical trial based on favorable preclinical assessment, only to fail in subsequent clinical trials of human stroke patients. The recent successful development of thrombectomy for acute ischemic stroke generated considerable enthusiasm for re-testing treatment candidates in combination with thrombectomy. Thus, SPAN is intended to screen and select highly promising treatment candidates for possible further study in human clinical trials.

UI Team

Anil K. Chauhan

Principal Investigator

Enrique Leira

Principal Investigator

Rakesh B. Patel

Research Assistant Professor

(co-Investigator)

Mariia Kumskova

Research Assistant Professor

(co-Investigator)

Daniel Thedens

Faculty, MRI

Aditi Jain

Post-doc

Abhishek Jha

Post-doc

News

NIH News: NIH-funded study led by Enrique Leira, MD, and Anil Chauhan, PhD, at the University of Iowa identifies potential new stroke treatment (March 2025)

NIH News: Researchers develop new method to identify potential stroke therapies (September, 2023)

Innovations in stroke care: UI-led study shows promise for protecting brain tissue (March, 2023)

Congratulations to IOWA-SPAN Team! Final Result: Uric acid (16mg/kg) given intravenously at the time of reperfusion was found to be cerebroprotective in a multi-center pre-clinical trial (SPAN) (February 2023)

Chauhan, Leira to lead stroke research site at Iowa (August, 2019)

Publications

The Stroke Preclinical Assessment Network Multi-laboratory Model of Thromboembolic Stroke with Thrombolysis: TE-MCAo. Bhuiyan M, Lin M, McCurry C, LambJ, Diniz MA, Bedirian K, Chauhan AK, Jha A, Jain A, Leira EC, Khan MB, Kamat PK, Hess DC, Sheng H, Hu B, Sansing LH, Ayata C, Imai T, Lynch K, Lyden P. J Vis Exp. 2025 Dec 19:(226). doi: 10.3791/69522.

Evaluating Tocilizumab in Ischemic Stroke: Findings from the SPAN multicenter trial. Chauhan A, LeeAE, Patel RB, Kumskova M, Leira EC, Chauhan AK, Shi Y, Cao S, Koehler RC, Dhandapani KM, Khan MB, Kamat PK, Arbab A, Hess DC, Herman AL, Boisserand L, Sansing LH, Morais A, Jin X, Aykan S, Imai T, Ayata C, Nagarkatti KA, Lamb J, Diniz MA, Lyden PD, McCullough LD, Aronowski J. Neuropharmacology. 2026 Mar 1:285:110801. doi: 10.1016/j.neuropharm.2025.110801

Fingolimod as a Potential Cerebroprotectant Results From the Stroke Preclinical Assessment Network. Boisserand LSB, Herman AL, Sanganahalli BG, Mihailovic J, Beatty HE, Johnson CW, Diaz S, DeLong JH, Velazquez S, Grutzendler J, Dela Cruz C, Zhou J, Sheth KN, Matouk C, Zhan S, Morais A, Imai T, Chauhan A, Patel RB, Kumskova M, Shi Y, Avery BD, Lamb J, Nagarkatti KA, Khan MB, Kamat PK, Dhandapani KM, McCullough LD, Aronowski J, Hess D, Koehler RC, Lyden P, Leira EC, Chauhan AK, Ayata C, Chen M, Diniz MA, Hyder F, Sansing LH, on behalf of the SPAN Investigators. Stroke. 2025 Nov;56(11):3280-3293. doi: 10.1161/STROKEAHA.125.050903

Multicenter SPAN Trial of Fasudil in Ischemic Stroke. Imai T., Morais A., Jin X., Qin T., Lamb J., Nagarkatti K., Chen M., Boisserand L.SB, Patel R.B., Kumskova M., Chauhan A., Dhandapani K.M., Khan M.B., Kamat P.K., Shi Y., Cao S., Sanganahalli B.G., Mandeville J.B., Lyden P.D., Hess D.C., Leira E.C., Chauhan A.K., Aronowski J., McCullough L.D., Koehler R., Sansing L.H., Diniz M.A., Ayata C., and SPAN Investigators. Stroke. 2025;56:2306–2317. doi: 10.1161/STROKEAHA.125.050977

Determinants of Outcome After Endovascular Middle Cerebral Artery Occlusion in Rats in the SPAN Trial. Jin X., Morais A., Imai T., Lamb J., Nagarkatti K., Boisserand L.SB, Beatty H., Sansing L.H., Khan M.B., Dhandapani K., Kamat P., Hess D.C., Patel R.B., Kumskova M., Chauhan A.K., McCullough L.D., Aronowski J., Leira E.C., Shi Y., Avery B.D., Koehler R.C., Lyden P.D., Ayata C. Stroke. 2025;56:00–00. doi: 10.1161/STROKEAHA.125.051235

Uric acid stroke cerebroprotection transcended sex, age, and comorbidities in a multicenter preclinical trial. Stroke. Patel RB, Kumskova M, Kodali H, Budnik I, Kuznetsov V, Jain A, Jha A, Thedens D, Dhanesha N, Sutariya B, Nagarkatti KA, Lamb J, Kamat P, Shi Y, Avery B, Imai T, Jin X, Chauhan A, Boisserand LSB, Khan MB, Dhandapani K, Sanganahalli BG, Sansing LH, Hess DC, Koehler RC, McCullough LD, Aronowski J, Ayata C, Diniz MA, Lyden PD, Planas AM, Chamorro A, Chauhan AK, Leira EC, on behalf of the SPAN Investigators. Stroke. 2025;56:965–973. DOI: 10.1161/STROKEAHA.124.048748

Biological and Procedural Predictors of Outcome in the Stroke Preclinical Assessment Network (SPAN) Trial. Morais A, Imai T, Jin X, Locascio JJ, Boisserand L, Herman AL, Chauhan A, Lamb J, Nagarkatti K, Diniz MA, Kumskova M, Dhanesha N, Kamat PK, Badruzzaman Khan M, Dhandapani KM, Patel RB, Sutariya B, Shi Y, van Leyen K, Kimberly WT, Hess DC, Aronowski J, Leira EC, Koehler RC, Chauhan AK, Sansing LH, Lyden PD, Ayata C. Circ Res. 2024 Aug 16;135(5):575-592. doi:10.1161/CIRCRESAHA.123.324139.

A multi-laboratory preclinical trial in rodents to assess treatment candidates for acute ischemic stroke. Lyden PD, Diniz, MA Bosetti F, Lamb J, Nagarkatti KA, Rogatko A, Kim S, Cabeen RP, Koenig JI, Akhter K, Arbab AS, Avery BD, Beatty HE, Bibic A, Cao S, Boisserand LSB, Chamorro A, Chauhan A, Diaz-Perez S, Dhandapani K, Dhanesha N, Goh A, Herman AL, Hyder F, Imai T, Johnson CW, Khan MB, Kamat P, Karuppagounder SS, Kumskova M, Mihailovic JM, Mandeville JB, Morais A, Patel RB, Sanganahalli BG, Smith C, Shi Y, Sutariya B, Thedens D, Qin T, Velazquez SE, Aronowski J, Ayata C, Chauhan AK, Leira EC, Hess DC, Koehler RC, McCullough LD, Sansing LH. Science Translational Medicine. 15, eadg8656 (2023) doi:10.1126/scitranslmed.adg8656

Embracing Heterogeneity in The Multicenter Stroke Preclinical Assessment Network (SPAN) Trial. Morais A, Locascio JJ, Sansing LH, Lamb J, Nagarkatti K, Imai T, van Leyen K, Aronowski J, Koenig JI, Bosetti F, Lyden P, Ayata C. Stroke. 2023 Feb;54(2):620-631. doi: 10.1161/STROKEAHA.122.040638

The Stroke Preclinical Assessment Network: Rationale, Design, Feasibility, and Stage 1 Results. Lyden PD, Bosetti F, Diniz MA, Rogatko A, Koenig JI, Lamb J, Nagarkatti KA, Cabeen RP, Hess DC, Kamat PK, Khan MB, Wood K, Dhandapani K, Arbab AS, Leira EC, Chauhan AK, Dhanesha N, Patel RB, Kumskova M, Thedens D, Morais A, Imai T, Qin T, Ayata C, Boisserand LSB, Herman AL, Beatty HE, Velazquez SE, Diaz-Perez S, Sanganahalli BG, Mihailovic JM, Hyder F, Sansing LH, Koehler RC, Lannon S, Shi Y, Karuppagounder SS, Bibic A, Akhter K, Aronowski J, McCullough LD, Chauhan A, Goh A; SPAN Investigators. Stroke. 2022 May;53(5):1802-1812. doi: 10.1161/STROKEAHA.121.038047

SPAN 1.0

UI stroke researchers led by Enrique Leira, MD, professor of neurology, and neurosurgery, and Anil Chauhan, PhD, professor of internal medicine, contributed the winning therapy in the rigorous pre-clinical Stroke Preclinical Assessment Network (SPAN) trial for testing cerebroprotective stroke treatments.

The UI-proposed therapy of uric acid supplementation was the only one of six options tested to succeed in minimizing brain tissue damage that can occur at the time of a stroke or when blood flow to the brain is restored (a process referred to as reperfusion.)

To better understand the importance and benefits of this research, Leira and Chauhan collaborated to explain the significance of their research. Both researchers contributed to the following responses.

SPAN 1.0 team: Enrique Leira (PI), Anil K. Chauhan (PI), Nirav Dhanesha (Co-I, Research Assistant Prof), Rakesh B Patel (Post-doc), Brijesh Sutariya (Post-doc), Mariia Kumskova (Post-doc), Daniel Thedens (Faculty, MRI), Angel Chamorro (Cons)