In the field of stroke thrombectomy, ineffective clinical and angiographic reperfusion after successful recanalization has drawn attention. Partial or complete microcirculatory reperfusion failure after the achievement of full patency of a former obstructed large vessel, known as the “no‐reflow phenomenon” or “microvascular obstruction,” was first reported in the 1960s and was later detected in both experimental models and patients with stroke. The no‐reflow phenomenon (NRP) was reported to result from intraluminal occlusions formed by blood components and extraluminal constriction exerted by the surrounding structures of the vessel wall. More recently, an emerging number of clinical studies have estimated the prevalence of the NRP in stroke patients following reperfusion therapy, ranging from 3.3% to 63% depending on its evaluation methods or study population. Studies also demonstrated its detrimental effects on infarction progress and neurological outcomes. In this review, we discuss the research advances, underlying pathogenesis, diagnostic techniques, and management approaches concerning the no‐reflow phenomenon in the stroke population to provide a comprehensive understanding of this phenomenon and offer references for future investigations.

Acute ischemic stroke is a leading cause of death and disability worldwide. Therapeutic hypothermia has long been considered as one of the most robust neuroprotective strategies. Although the neuroprotective effects of hypothermia have only been confirmed in patients with global cerebral ischemia after cardiac arrest and in neonatal hypoxic ischemic encephalopathy, establishing standardized protocols and strictly controlling the key parameters may extend its application in other brain injuries, such as acute ischemic stroke. In this review, we discuss the potential neuroprotective effects of hypothermia, its drawbacks evidenced in previous studies, and its potential clinical application for acute ischemic stroke especially in the era of reperfusion. Based on the different conditions between bench and bedside settings, we demonstrate the importance of vascular recanalization for neuroprotection of hypothermia by analyzing numerous literatures regarding hypothermia in focal cerebral ischemia. Then, we make a thorough analysis of key parameters of hypothermia and introduce novel hypothermic therapies. We advocate in favor of the process of clinical translation of intra-arterial selective cooling infusion in the era of reperfusion and provide insights into the prospects of hypothermia in acute ischemic stroke.

Remote ischemic conditioning (RIC) has been investigated as a promising, safe, and well-tolerated nonpharmacological therapy for cardio-cerebrovascular disease over the past 3 decades; variable results have been found when it is used in cerebrovascular versus cardiovascular disease. For patients with cardiovascular disease, milestone studies suggest that the roles of RIC may be limited. Recently, however, 2 large trials investigating RIC in patients with cerebrovascular disease found promising results, which may reignite the field’s research prospects after its setbacks in the cardiovascular field. This perspectives article highlights several important clinical trials of RIC in the cardio-cerebrovascular disease and describes the many challenges of RIC in clinical translation. Finally, based on the available evidence, several promising research directions such as chronic RIC, early initiation in target population, improvement of compliance, better understanding of dosing, and identification of specific biomarkers are proposed and should be investigated before RIC can become applied into clinical practice for patient benefit.

Rationale: There are no randomized trials examining the best treatment for acute basilar artery occlusion in the 6–24-hour time window. Aims: To assess the safety and efficacy of thrombectomy for stroke due to basilar artery occlusion in patients randomized within 6–24 h from symptom onset or time last seen well. Sample size: For an estimated difference of 20% in proportions of the primary outcome between the two groups, 318 patients will be included for 5% significance and 90% power with a planned interim analysis after two-thirds of the sample size (212 patients) have achieved the 90 days follow-up. Methods and design: A prospective, multi-center, randomized, controlled, open-label and blinded-endpoint trial. The randomization employs a 1:1 ratio of mechanical thrombectomy with the detachable Solitaire thrombectomy device and best medical therapy (BMT) vs. BMT alone. Study outcomes: The primary outcome will be the proportion of patients achieving modified Rankin Scale (mRS) 0–3 at 90 days. Key secondary outcomes are: dramatic early favorable response, dichotomized mRS score (0–2 vs. 3–6 and 0–4 vs. 5–6) at 90 days, ordinal (shift) mRS analysis at 90 days, infarct volume at 24 h, vessel recanalization at 24 h in both treatment arms, and successful recanalization in the thrombectomy arm according to the modified thrombolysis in cerebral infarction (mTICI) classification defined as mTICI 2 b or 3. Safety variables are mortality at 90 days, symptomatic intracranial hemorrhage rates at 24 h, and procedure-related complications. Discussion: Results from this trial will indicate whether mechanical thrombectomy is superior to medical management alone in achieving favorable outcomes in subjects with acute stroke caused by basilar artery occlusion presenting within 6–24 h from symptom onset. Trial registration: URL: http://www.clinicaltrials.gov . ClinicalTrials.gov Identifier: NCT02737189.

Reperfusion therapy, which substantially promotes the vessel recanalization rate and improves clinical outcomes, remains the most effective treatment of acute ischemic stroke (AIS). However, a substantial number of patients are either unsuitable for recanalization therapy or experience limited recovery postreperfusion. There is growing recognition that adjunctive neuroprotective therapies may further improve the outcomes in AIS patients by protecting brain tissue during ischemia. Recent advancements in neuroprotective approaches, including pharmacologic agents such as nerinetide edaravone, and uric acid, as well as nonpharmacological interventions, such as remote ischemic conditioning and normobaric hyperoxia, offer promising potentials in stroke care. This review provides an overview of the current neuroprotective therapies, examines recent clinical evidence, and discusses the strengths and weaknesses of certain clinical trials aimed at cerebral protection.

Background: Remote ischemic conditioning can promote hematoma resolution, attenuate brain edema, and improve neurological recovery in animal models of intracerebral hemorrhage. Aims: This study aimed to evaluate the safety and preliminary efficacy of remote ischemic conditioning in patients with intracerebral hemorrhage. Methods: In this multicenter, randomized, controlled trial, 40 subjects with supratentorial intracerebral hemorrhage presenting within 24–48 h of onset were randomly assigned to receive medical therapy plus remote ischemic conditioning for consecutive seven days or medical therapy alone. The primary safety outcome was neurological deterioration within seven days of enrollment, and the primary efficacy outcome was the changes of hematoma volume on CT images. Other outcomes included hematoma resolution rate at 7 days ([hematoma volume at 7 days − hematoma volume at baseline]/hematoma volume at baseline), perihematomal edema (PHE), and functional outcome at 90 days. Results: The mean age was 59.3 ± 11.7 years and hematoma volume was 13.9 ± 4.5 mL. No subjects experienced neurological deterioration within seven days of enrollment, and no subject died or experienced remote ischemic conditioning-associated adverse events during the study period. At baseline, the hematoma volumes were 14.19 ± 5.07 mL in the control group and 13.55 ± 3.99 mL in the remote ischemic conditioning group, and they were 8.54 ± 3.99 mL and 6.95 ± 2.71 mL at seven days after enrollment, respectively, which is not a significant difference ( p > 0.05 each). The hematoma resolution rate in the remote ischemic conditioning group (49.25 ± 9.17%) was significantly higher than in the control group (41.92 ± 9.14%; MD, 7.3%; 95% CI, 1.51–13.16%; p = 0.015). The absolute PHE volume was 17.27 ± 8.34 mL in the control group and 12.92 ± 7.30 mL in the remote ischemic conditioning group at seven days after enrollment, which is not a significant between-group difference ( p = 0.087), but the relative PHE in the remote ischemic conditioning group (1.77 ± 0.39) was significantly lower than in the control group (2.02 ± 0.27; MD, 0.25; 95% CI, 0.39–0.47; p = 0.023). At 90-day follow-up, 13 subjects (65%) in the remote ischemic conditioning group and 12 subjects (60%) in the control group achieved favorable functional outcomes (modified Rankin Scale score ≤ 3), which is not a significant between-group difference ( p = 0.744). Conclusions: Repeated daily remote ischemic conditioning for consecutive seven days was safe and well tolerated in patients with intracerebral hemorrhage, and it may be able to improve hematoma resolution rate and reduce relative PHE. However, the effects of remote ischemic conditioning on the absolute hematoma and PHE volume and functional outcomes in this patient population need further investigations. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT03930940.