Tissue Clock Beyond Time Clock: Endovascular Thrombectomy for Patients With Large Vessel Occlusion Stroke Beyond 24 Hours.

BACKGROUND AND PURPOSE: Randomized trials proved the benefits of mechanical thrombectomy (MT) for select patients with large vessel occlusion (LVO) within 24 hours of last-known-well (LKW). Recent data suggest that LVO patients may benefit from MT beyond 24 hours. This study reports the safety and outcomes of MT beyond 24 hours of LKW compared to standard medical therapy (SMT). METHODS: This is a retrospective analysis of LVO patients presented to 11 comprehensive stroke centers in the United States beyond 24 hours from LKW between January 2015 and December 2021. We assessed 90-day outcomes using the modified Rankin Scale (mRS). RESULTS: Of 334 patients presented with LVO beyond 24 hours, 64% received MT and 36% received SMT only. Patients who received MT were older (67±15 vs. 64±15 years, P=0.047) and had a higher baseline National Institutes of Health Stroke Scale (NIHSS; 16±7 vs.10±9, P<0.001). Successful recanalization (modified thrombolysis in cerebral infarction score 2b-3) was achieved in 83%, and 5.6% had symptomatic intracranial hemorrhage compared to 2.5% in the SMT group (P=0.19). MT was associated with mRS 0-2 at 90 days (adjusted odds ratio [aOR] 5.73, P=0.026), less mortality (34% vs. 63%, P<0.001), and better discharge NIHSS (P<0.001) compared to SMT in patients with baseline NIHSS ≥6. This treatment benefit remained after matching both groups. Age (aOR 0.94, P<0.001), baseline NIHSS (aOR 0.91, P=0.017), Alberta Stroke Program Early Computed Tomography (ASPECTS) score ≥8 (aOR 3.06, P=0.041), and collaterals scores (aOR 1.41, P=0.027) were associated with 90-day functional independence. CONCLUSION: In patients with salvageable brain tissue, MT for LVO beyond 24 hours appears to improve outcomes compared to SMT, especially in patients with severe strokes. Patients' age, ASPECTS, collaterals, and baseline NIHSS score should be considered before discounting MT merely based on LKW.

Cerebral endothelial cell-derived small extracellular vesicles enhance neurovascular function and neurological recovery in rat acute ischemic stroke models of mechanical thrombectomy and embolic stroke treatment with tPA.

Treatment of patients with cerebral large vessel occlusion with thrombectomy and tissue plasminogen activator (tPA) leads to incomplete reperfusion. Using rat models of embolic and transient middle cerebral artery occlusion (eMCAO and tMCAO), we investigated the effect on stroke outcomes of small extracellular vesicles (sEVs) derived from rat cerebral endothelial cells (CEC-sEVs) in combination with tPA (CEC-sEVs/tPA) as a treatment of eMCAO and tMCAO in rat. The effect of sEVs derived from clots acquired from patients who had undergone mechanical thrombectomy on healthy human CEC permeability was also evaluated. CEC-sEVs/tPA administered 4 h after eMCAO reduced infarct volume by ∼36%, increased recanalization of the occluded MCA, enhanced cerebral blood flow (CBF), and reduced blood-brain barrier (BBB) leakage. Treatment with CEC-sEVs given upon reperfusion after 2 h tMCAO significantly reduced infarct volume by ∼43%, and neurological outcomes were improved in both CEC-sEVs treated models. CEC-sEVs/tPA reduced a network of microRNAs (miRs) and proteins that mediate thrombosis, coagulation, and inflammation. Patient-clot derived sEVs increased CEC permeability, which was reduced by CEC-sEVs. CEC-sEV mediated suppression of a network of pro-thrombotic, -coagulant, and -inflammatory miRs and proteins likely contribute to therapeutic effects. Thus, CEC-sEVs have a therapeutic effect on acute ischemic stroke by reducing neurovascular damage.

Understanding the Radial Force of Stroke Thrombectomy Devices to Minimize Vessel Wall Injury: Mechanical Bench Testing of the Radial Force Generated by a Novel Braided Thrombectomy Assist Device Compared to Laser-Cut Stent Retrievers in Simulated MCA Vessel Diameters.

BACKGROUND: Recent reports have raised various concerns about the risk of vessel wall injury while withdrawing current laser-cut stent retrievers during active strut apposition to the vessel walls. The development of braided thrombectomy assist devices in conjunction with aspiration systems may be gentler on the fragile brain vessels and more optimized with regard to the radial force (RF) for vessel diameters of proximal (M1) and distal (M2) large vessel occlusions (LVOs). METHODS: Mechanical bench testing of the RF was performed using a radial compression station mounted on a tensile testing machine. The total RF in newtons (N) generated in vessels with diameters ranging from 2.25 to 3 mm as seen in proximal LVOs (∼M1), and in vessel diameters ranging from 1.5 to 2.24 mm as seen in distal LVOs (∼M2), was measured. The outer diameter of each stent was recorded, and an RF ≤1 N was grouped as "low," while an RF >1 N was grouped as "high" for this analysis. RESULTS: The total RFs of all laser-cut stent retrievers were all higher in the simulated M2 vessels (>1 N) than in the M1 vessels (<1 N), whereas the total RFs of the braided thrombectomy assist devices were uniformly low in both the simulated M1 and the simulated M2 vessels. CONCLUSIONS: Novel braided thrombectomy assist devices in conjunction with aspiration systems have lower RFs than existing laser-cut stent retrievers in M1 and M2 vessel diameters. Further in vivo studies are needed to delineate the impact of lowering the RF on vessel wall integrity.