Microcirculation No-Reflow Phenomenon after Acute Ischemic Stroke

Abstract

<b><i>Background:</i></b> The no-reflow phenomenon refers to a failure to restore normal cerebral microcirculation despite brain large artery recanalization after acute ischemic stroke, which was observed over 50 years ago. <b><i>Summary:</i></b> Different mechanisms contributing to no-reflow extend across the endovascular, vascular wall, and extravascular factors. There are some clinical tools to evaluate cerebral microvascular hemodynamics and represent biomarkers of the no-reflow phenomenon. As substantial experimental and clinical data showed that clinical outcome was better correlated with reperfusion status rather than recanalization in patients with ischemic stroke, how to address the no-reflow phenomenon is critical. But effective treatments for restoring cerebral microcirculation have not been well established until now, so there is an urgent need for novel therapeutic perspectives to improve outcomes after recanalization therapies. <b><i>Conclusion:</i></b> Here, we review the occurrence of the no-reflow phenomenon after ischemic stroke and discuss its impact, detection method, and therapeutic strategies on the course of ischemic stroke, from basic science to clinical findings.

Systemic biomarker associated with poor outcome after futile reperfusion

“…The no‐reflow phenomenon has been described both in the heart and brain after the successful removal of vascular obstruction, although the mechanics involved in this process present some differences between them 31 . In ischemic stroke, the main causes associated with reperfusion failure include, among others, microvascular occlusion with clot material, pericytes contraction, and death, endothelial cell oedema, capillary obstruction with neutrophils, and vasoconstriction 31–33 …”

No-reflow phenomenon following stroke recanalization therapy: Clinical assessment advances: A narrative review

“…[ 49 ] Even when recanalization is achieved and the cerebral infarction volume is small, a significant increase in cerebral microvascular resistance in the ischemic area still supports the existence of the NRP in the microcirculation after recanalization. [ 2 ] Moreover, the increase in the TCD PI after recanalization indicates that increased microvascular resistance in the ischemic region often occurs after successful recanalization, suggesting that the PI could be a readily available clinical biomarker for the NRP. [ 20 ] In 2022, a study demonstrated that an increased MCA PI in patients with AIS after thrombectomy, as measured using TCD ultrasound, was associated with a poor prognosis.…”

“…In clinical practice, shortening the door-to-puncture time, using thrombus aspiration if necessary to reduce thrombus burden, avoiding repeated thrombectomy operations, and controlling blood pressure, blood sugar, and so on can prevent the NRP by reducing brain tissue injury. [ 2 ] Once the NRP is identified by the above monitoring methods, remedial occupational therapy options should be applied as soon as possible, such as by administering adenosine to reduce the resistance of small arteries, platelet glycoprotein IIb/IIIa receptor antagonists to inhibit platelet aggregation, and vasodilator drugs to dilate the responsible vessels. [ 58 ] These interventions aim to enhance patient recovery and improve long-term prognosis.…”

“…This phenomenon is commonly referred to as the “no-reflow phenomenon” (NRP). [ 2 ] Currently, there is no unified standard for diagnosing and evaluating the NRP in clinical patients to guide its prevention and treatment. Therefore, this review examined the existing clinical strategies for assessing the NRP.…”

Exosomal microRNAs: implications in the pathogenesis and clinical applications of subarachnoid hemorrhage

“…Cerebral microcirculation is primarily based on the BBB’s structural and functional basis, comprising vascular endothelial cells, endothelium-cell junctions, the basement membrane, and astrocytes ( Kondo et al, 2022 ; Yang et al, 2022 ; Hu et al, 2023 ). Recently, considerable attention has been given to the role of cerebral microcirculation disturbances in EBI following SAH.…”