Leptomeningeal collaterals regulate reperfusion in ischemic stroke and rescue the brain from futile recanalization

Recanalization is the mainstay of ischemic stroke treatment. However, even with timely clot removal, many stroke patients recover poorly. Leptomeningeal collaterals (LMCs) are pial anastomotic vessels with yet-unknown functions. We applied laser speckle imaging, ultrafast ultrasound, and two-photon microscopy in a thrombin-based mouse model of stroke and fibrinolytic treatment to show that LMCs maintain cerebral autoregulation and allow for gradual reperfusion, resulting in small infarcts. In mice with poor LMCs, distal arterial segments collapse, and deleterious hyperemia causes hemorrhage and mortality after recanalization. In silico analyses confirm the relevance of LMCs for preserving perfusion in the ischemic region. Accordingly, in stroke patients with poor collaterals undergoing thrombectomy, rapid reperfusion resulted in hemorrhagic transformation and unfavorable recovery. Thus, we identify LMCs as key components regulating reperfusion and preventing futile recanalization after stroke. Future therapeutic interventions should aim to enhance collateral function, allowing for beneficial reperfusion after stroke. [Display omitted] •LMCs maintain perfusion during stroke•Upon recanalization, LMCs allow for a gradual reperfusion•In mice with poor LMCs, recanalization causes deleterious hyperperfusion•Stroke patients with poor LMCs show fast reperfusion and futile recanalization Futile recanalization is a serious problem for stroke treatments. Binder and El Amki et al. demonstrate that leptomeningeal collaterals (LMCs) regulate reperfusion after stroke. Mice with poor LMCs developed rapid, uncontrolled hyperperfusion. In stroke patients, they found a similar deleterious reperfusion. Collateral function should be target of novel stroke treatments.