Transplantation of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has been reported to ameliorate functional deficits after cerebral artery occlusion in rats. Although several hypotheses to account for these therapeutic effects have been suggested, current thinking is that both neuroprotection and angiogenesis are primarily responsible. In this study, we compared the effects of hMSCs and angiopoietin-1 gene-modified hMSCs (Ang-hMSCs) intravenously infused into rats 6 h after permanent middle cerebral artery occlusion. Magnetic resonance imaging and histologic analyses revealed that rats receiving hMSCs or Ang-hMSCs exhibited comparable reduction in gross lesion volume as compared with the control group. Although both cell types indeed improved angiogenesis near the border of the ischemic lesions, neovascularization and regional cerebral blood flow were greater in some border areas in Ang-hMSC group. Both hMSC-and Ang-hMSC-treated rats showed greater improved functional recovery in the treadmill stress test than did control rats, but the Ang-hMSC group was greater. These results indicate the intravenous administration of genetically modified hMSCs to express angiopoietin has a similar effect on reducing lesion volume as hMSCs, but the Ang-hMSC group showed enhanced regions of increased angiogenesis at the lesion border, and modest additional improvement in functional outcome.

BackgroundEndovascular therapy has been shown to be effective in patients with acute cerebral large‐vessel occlusion, but real‐world efficacies are unknown.Methods and ResultsWe conducted a prospective registry at 46 centers between October 2014 and January 2017. Eligible patients were those who were aged 20 years or older, with acute cerebral large‐vessel occlusion, and who were hospitalized within 24 hours of the onset. We enrolled both consecutive patients who were treated with or without endovascular therapy. Endovascular therapy included thrombectomy, balloon angioplasty, stenting, local fibrinolysis, and piercing. The primary outcome was a favorable outcome as defined by a modified Rankin Scale of 0 to 2 at 90 days after onset. Secondary outcomes were modified Rankin Scale of 0 to 1 and mortality. Safety outcomes were intracerebral hemorrhage or a recurrence of ischemic stroke. We constructed the 2242 (1121 each) propensity score–matched patients cohort based on a propensity score for endovascular therapy and estimated the adjusted odds ratio, followed by sensitivity analyses on original 2399 (1278 in endovascular therapy versus 1121 in no endovascular therapy) patients. In the propensity score–matched cohort, favorable outcomes were observed in 35.3% and 30.7% of patients in the endovascular therapy and no endovascular therapy groups, respectively (P=0.02). The adjusted odds ratio for the favorable outcome was 1.44 (95% confidence interval, 1.10–1.86, P=0.007). The efficacy of endovascular therapy in achieving favorable outcomes did not differ between our subgroups and in the sensitivity analyses.ConclusionsEndovascular therapy decreased disabilities at 90 days in real‐world patients with acute cerebral large‐vessel occlusion.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT02419794.

Background and Purpose— The treatment and prognosis of acute large vessel occlusion with mild symptoms have not been sufficiently studied. The present study aimed to investigate the clinical or radiological predictors of clinical outcome in patients with stroke with mild symptoms due to acute large vessel occlusion. Methods— Of 2420 patients with acute large vessel occlusion in the RESCUE-Japan Registry 2 (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism-Japan Registry 2), a multicenter prospective registry in Japan, patients with modified Rankin Scale scores of 0 to 2 before onset and initial National Institutes of Health Stroke Scale (NIHSS) scores of 0 to 5 were examined in post hoc analysis. We examined the clinical and radiological characteristics associated with a favorable outcome (modified Rankin Scale score, 0–2 at 90 days) using multivariate analysis, as well as the factors associated with a favorable outcome in patients treated with endovascular therapy. Results— We analyzed 272 patients (median age, 73 years; median NIHSS score on admission, 3). Eighty-six (31.6%) patients were treated with intravenous recombinant tissue-type plasminogen activator, 54 (19.9%) underwent endovascular therapy, and 208 (76.5%) showed a favorable outcome. In multivariate analysis, age <75 years (odds ratio [OR], 2.42 [95% CI, 1.30–4.50]), initial NIHSS score 0 to 3 (OR, 3.08 [95% CI, 1.59–5.98]), intravenous recombinant tissue-type plasminogen activator (OR, 2. 86 [95% CI, 1.32–6.21]), and blood glucose level ≤140 mg/dL (OR, 2.37 [95% CI, 1.22–4.60]) were independently associated with a favorable outcome. However, endovascular therapy was not associated with a favorable outcome (OR, 1.65 [95% CI, 0.71–3.88]). Among 54 patients treated with endovascular therapy, good reperfusion status was more common in the favorable outcome group (88.6% versus 60.0%; P <0.05). Conclusions— Younger age, lower initial NIHSS score, intravenous recombinant tissue-type plasminogen activator, and absence of hyperglycemia were independently associated with a favorable outcome in patients with acute large vessel occlusion with low NIHSS scores. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02419794.

Background and Purpose— Endovascular therapy (EVT) is strongly recommended for acute cerebral large vessel occlusion with the Alberta Stroke Program Early CT Score (ASPECTS) ≥6 due to occlusion of the internal carotid artery or M1 segment of the middle cerebral artery. However, the effect of EVT for patients who have ischemic core with ASPECTS ≤5 (0–5) was not established. The purpose of this study was to elucidate the outcomes of EVT for patients with large ischemic core. Methods— Based on the data of The Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism Japan Registry 2, patients with internal carotid artery or M1 segment of the middle cerebral artery occlusion and pretreatment ASPECTS 0 to 5 on noncontrast CT or diffusion-weighted image were extracted, and the outcomes by EVT were analyzed. Primary end point was defined as a good functional outcome (modified Rankin Scale score of ≤2) after 90 days. Result— Among 2420 registered patients, 504 patients were with internal carotid artery or M1 segment of the middle cerebral artery occlusion and ASPECTS 0 to 5. Among these 504 patients, 172 (34.1 %) were treated with EVT (EVT group) and 332 (65.9 %) without (no-EVT group). In the no-EVT group, elderly patients, females, poor prestroke modified Rankin Scale, high National Institutes of Health Stroke Scale, low ASPECTS, and late admission were significantly more observed. Good functional outcomes were significantly more observed in the EVT group than in the no-EVT group (19.8 % versus 4.2 %; P <0.0001; adjusted odds ratio, 2.33; 95% CI, 1.10–4.94). The incidences of symptomatic intracranial hemorrhage within 72 hours did not significantly different between the EVT group and the no-EVT group (3.7 % versus 4.9%; P =0.55; adjusted odds ratio, 0.50; 95% CI, 0.14–1.73). Conclusions— Although outcomes in this group of patients were usually poor, the data suggested EVT may increase the likelihood of a good functional outcome.

In the patients who underwent CAS for vulnerable carotid stenosis, double balloon protection was an independent significant factor associated with a reduction in the risk of new lesions on DWI after the procedure compared to conventional distal protections.