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

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.

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.