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Review
. 2025 Jun 22.
doi: 10.1007/s11239-025-03135-w. Online ahead of print.

From "time is brain" to "time is collaterals": updates on the role of cerebral collateral circulation in stroke

Mangiardi Marilena #  1 , Pezzella Francesca Romana #  2 , Alfano Guido  3 , De Rubeis Gianluca  4 , Fabiano Sebastiano  4 , Pampana Enrico  4 , Anticoli Sabrina  2
Affiliations
Review

From "time is brain" to "time is collaterals": updates on the role of cerebral collateral circulation in stroke

Mangiardi Marilena et al. J Thromb Thrombolysis. .

Abstract

Background: Acute ischemic stroke (AIS) remains the leading cause of mortality and disability worldwide. While revascularization therapies-such as intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT)-have significantly improved outcomes, their success is strongly influenced by the status of cerebral collateral circulation. Collateral vessels sustain cerebral perfusion during vascular occlusion, limiting infarct growth and extending therapeutic windows. Despite this recognized importance, standardized methods for assessing collateral status and integrating it into treatment strategies are still evolving. This narrative review synthesizes current evidence on the role of collateral circulation in AIS, focusing on its impact on infarct dynamics, treatment efficacy, and functional recovery. We highlight findings from major clinical trials-including MR CLEAN, DAWN, DEFUSE-3, and SWIFT PRIME which consistently demonstrate that robust collateral networks are associated with improved outcomes and expanded eligibility for reperfusion therapies. Advances in neuroimaging, such as multiphase CTA and perfusion MRI, alongside emerging AI-driven automated collateral grading, are reshaping patients' selection and clinical decision-making. We also discuss novel therapeutic strategies aimed at enhancing collateral flow, such as vasodilators, neuroprotective agents, statins, and stem cell therapies. Despite growing evidence supporting collateral-based treatment approaches, real-time clinical implementation remains limited by challenges in standardization and access.

Conclusion: Cerebral collateral circulation is a critical determinant of stroke prognosis and treatment response. Incorporating collateral assessment into acute stroke workflows-supported by advanced imaging, artificial intelligence, and personalized medicine-offers a promising pathway to optimize outcomes. As the field moves beyond a strict "time is brain" model, the emerging paradigm of "time is collaterals" may better reflect the dynamic interplay between perfusion, tissue viability, and therapeutic opportunity in AIS management.

Keywords: Acute ischemic stroke; Cerebral collateral circulation; Intravenous thrombolysis; Neuroimaging.; Thrombectomy.

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Conflict of interest statement

Declarations. Human and animal rights and informed consent: This article does not contain any studies with human or animal subjects performed by any of the authors. Conflict of interest: All authors declare that they have no potential conflicts of interest. Competing interests: The authors declare no competing interests.

References

    1. Saini V, Guada L, Yavagal DR (2021) Global Epidemiology of Stroke and Access to Acute Ischemic Stroke Interventions. Neurology. Nov 16;97(20 Suppl 2): S6-S16. https://doi.org/10.1212/WNL.0000000000012781
    1. Xu J, Hou S, Chen Z, Liu Y, Deng X, Wang C, Liu S, Wang Y (2025) The burden of ischemic stroke in Eastern Europe from 1990 to 2021. BMC Neurol. Feb 22;25(1):74. https://doi.org/10.1186/s12883-025-04081-z
    1. GBD 2021 Stroke Risk Factor Collaborators (2024 Oct) Global, regional, and National burden of stroke and its risk factors, 1990–2021: a systematic analysis for the global burden of disease study 2021. Lancet Neurol 23(10):973–1003. https://doi.org/10.1016/S1474-4422(24)00369-7
    1. Mosconi MG, Paciaroni M (2022) Treatments in ischemic stroke: current and future. Eur Neurol 85(5):349–366. https://doi.org/10.1159/000525822 Epub 2022 Aug 2 - DOI - PubMed
    1. Berge E, Whiteley W, Audebert H, De Marchis GM, Fonseca AC, Padiglioni C, de la Ossa NP, Strbian D, Tsivgoulis G, Turc G (2021 Mar) European stroke organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke. Eur Stroke J 6(1):I–LXII. https://doi.org/10.1177/2396987321989865

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