Background The benefit of mechanical thrombectomy for an acute ischemic stroke involving M2 segment occlusion is not clear, especially when performed with second-generation thrombectomy devices. Method We reviewed the literature to investigate clinical outcomes and the rates of recanalization, symptomatic intracerebral hematoma, and mortality in mechanical thrombectomy performed using second-generation thrombectomy devices. We compared the outcomes between patients treated for M2 and M1 occlusions. Results Seven studies involving 805 patients with M2 thrombectomy were included in this meta-analysis. The functional independence rate 90 days after thrombectomy (modified Rankin Scale 0–2) was 59.3% (OR 1.81, 95% CI 1.74–1.88). The recanalization rate (thrombolysis in cerebral infarction 0–2) was 84.16% (OR 2.32, 95% CI 2.08–2.29). The symptomatic intracerebral hematoma rate was 4.9% (OR 1.05, 95% CI 1.03–1.09). The mortality was 7.7% (OR 1.08, 95% CI 1.03–1.13). The outcomes were better in patients with M2 occlusion than in those with M1 occlusion. In a subgroup analysis, we found that among patients with hypertension, mechanical thrombectomy achieved better functional outcomes and recanalization in M2 occlusion than M1 occlusion. Conclusion Mechanical thrombectomy performed with second-generation thrombectomy devices for M2 occlusion can provide a good functional outcome as well as satisfying recanalization. Moreover, there was no significant difference in the symptomatic intracerebral hematoma and mortality rates, suggesting this procedure is as safe in M2 occlusion as in M1 occlusion.

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Background and Purpose— Thrombolytic treatment of acute ischemic stroke with tPA (tissue-type plasminogen activator) is hampered by its narrow therapeutic window and potential hemorrhagic complication. Vepoloxamer is a nonionic surfactant that exerts potent hemorheologic and antithrombotic properties in various thrombotic diseases. The current study investigated the effect of vepoloxamer on tPA treatment in a rat model of embolic stroke. Methods— Male Wistar rats subjected to embolic middle cerebral artery occlusion were treated with the combination of vepoloxamer and tPA, vepoloxamer alone, tPA alone, or saline initiated 4 hours after middle cerebral artery occlusion. Results— Monotherapy with tPA did not reduce infarct volume, and adversely potentiated microvascular thrombosis and vascular leakage compared with the saline treatment. Vepoloxamer monotherapy reduced infarct volume by 25% and improved brain perfusion. However, the combination treatment with vepoloxamer and tPA significantly reduced infarct volume by 32% and improved neurological function, without increasing the incidence of gross hemorrhage. Compared with vepoloxamer alone, the combination treatment with vepoloxamer and tPA robustly reduced secondary thrombosis and tPA-augmented microvascular leakage and further improved brain perfusion, which was associated with substantial reductions of serum active PAI-1 (plasminogen activator inhibitor-1) level and tPA-upregulated PAI-1 in the ischemic brain. Mechanistically, exosomes derived from platelets of ischemic rats treated with tPA-augmented cerebral endothelial barrier permeability and elevated protein levels of PAI-1 and TF (tissue factor) in the endothelial cells, whereas exosomes derived from platelets of rats subjected to the combination treatment with vepoloxamer and tPA diminished endothelial permeability augmented by tPA and fibrin and reduced PAI-1 and TF levels in the endothelial cells. Conclusions— The combination treatment with vepoloxamer and tPA exerts potent thrombolytic effects in rats subjected to acute ischemic stroke. Vepoloxamer reduces tPA-aggravated prothrombotic effect of platelet-derived exosomes on cerebral endothelial cells, which may contribute to the therapeutic effect of the combination treatment.

Background: Perivascular adipose tissue (PVAT) imaging can be used in clinical practice as a surrogate marker of vascular disease. We aimed to analyze the association between the density of carotid artery PVAT and clinical features and outcomes in stroke patients treated with mechanical thrombectomy.Methods: A total of 183 consecutive patients treated with mechanical thrombectomy due to anterior circulation large vessel occlusion were retrospectively included from January 2016 to May 2021. The density of carotid artery PVAT was evaluated by preoperative computed tomography angiography. Successful arterial recanalization was defined as a modified Thrombolysis in Cerebral Infarction score of 2b-3 on the final angiographic examination. Poor functional outcome was defined as a modified Rankin Scale (mRS) score > 2 at 3 months after stroke. We assessed the independent effect of carotid artery PVAT density on revascularization, functional outcome, and mortality using logistic regression models adjusted for relevant confounders.Results: Patients with large artery atherosclerotic stroke have higher carotid artery PVAT density than patients with other stroke etiologies (–65.82 ± 12.96 vs. –75.77 ± 13.44, P < 0.001). Higher carotid artery PVAT density was associated with unsuccessful recanalization [adjusted odds ratio (AOR) (95% CI), 2.968 (1.292, 6.819), P = 0.010], and poor outcome [AOR (95% CI), 2.704 (1.610, 4.541), P < 0.001] and mortality [AOR (95% CI), 1.894 (1.040, 3.449), P = 0.037] at 3 months in stroke patients treated with thrombectomy.Conclusion: Higher carotid artery PVAT density before mechanical thrombectomy is an indicator of worse postprocedural arterial revascularization and a worse functional outcome in acute stroke patients.