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Stroke is a leading cause of adult disability. In our previous study, transplantation of human umbilical mesenchymal stem cells (HUMSCs) in Wharton's jelly in the acute phase of ischemic stroke promotes recovery in rats. Unfortunately, there is no cure for chronic stroke. Patients with chronic stroke can only be treated with rehabilitation or supportive interventions. This study aimed to investigate the potential of xenograft of HUMSCs for treating chronic stroke in rats. Rats were subjected to 90 min middle cerebral artery occlusion and then reperfusion to mimic ischemic cerebral stroke. On day 14 following stroke, HUMSCs were transplanted into the damaged cerebral cortex. The motor function in rats of the Stroke + HUMSCs group exhibited significant improvement compared to that of the Stroke + Saline group, and the trend persisted until day 56 post stroke. The cerebral cortex changes were tracked using magnetic resonance imaging, showing that cerebral atrophy was found starting on day 7 and was reduced significantly in rats receiving HUMSCs compared to that in the Stroke + Saline group from day 21 to day 56. HUMSCs were found to be existed in the rats' cerebral cortex on day 56, with signs of migration. The grafted HUMSCs did not differentiate into neurons or astrocytes and may release cytokines to improve neuroprotection, decrease inflammation and increase angiogenesis. Our results demonstrate that xeno-transplantation of HUMSCs has therapeutic benefits for chronic ischemic stroke. Most importantly, patients do not need to use their own HUMSCs, which is a gospel thing for clinical patients.

Background Insufficient evidence is available for patients with acute ischemic stroke with atrial fibrillation (AF) to determine the efficacy and safety of different dosages of intravenous thrombolysis treatment. This study examined clinical outcomes in Chinese patients with stroke with and without AF after intravenous thrombolysis treatment with different intravenous thrombolysis doses. Methods and Results This multicenter, prospective cohort study recruited 2351 patients with acute ischemic stroke (1371 with AF and 980 without AF) treated with intravenous thrombolysis using alteplase. The Totaled Health Risks in Vascular Events score is a validated risk-scoring tool used for assessing patients with acute ischemic stroke with and without AF. We evaluated favorable functional outcome at day 90 and symptomatic intracranial hemorrhage within 24 to 36 hours and outcomes of the patients receiving different doses of alteplase. Compared with the non-AF group, the AF group exhibited a 2- to 3-fold increased risk of symptomatic intracranial hemorrhage according to the National Institute of Neurological Disorders and Stroke standard (relative risk [RR], 2.10 [95% CI, 1.35-3.26]). Favorable functional outcome at 90 days and symptomatic intracranial hemorrhage rates according to the European Cooperative Acute Stroke Study II and the Safe Implementation of Thrombolysis in Stroke-Monitoring Study standards did not significantly differ between the AF and non-AF groups. In addition, the low-dose alteplase subgroup exhibited an increased risk of symptomatic intracranial hemorrhage according to the National Institute of Neurological Disorders and Stroke standard (RR, 2.84 [95% CI, 1.63-4.96]). A validation study confirmed these findings after adjustment for scores determined using different stroke risk-scoring tools. Conclusions Different alteplase dosages did not affect functional status at 90 days in the AF and non-AF groups. Thus, the adoption of low-dose alteplase simply because of AF is not recommended.

Familial hypercholesterolemia (FH) is a common genetic disorder characterized by a lifelong elevated low-density lipoprotein cholesterol (LDL-C) level. The relationship between FH and ischemic stroke is still controversial. We enrolled ischemic stroke patients prospectively in our neurological ward, and divided them into two groups according to LDL-C levels with a threshold of 130 mg/dl. Targeted sequencing was performed in all stroke patients for LDLR, APOB , and PCSK9 genes. The fifty-eight high-LDL subjects were older, prevalence of previous myocardial infarction/stroke history was lower, and the first stroke age was older compared with values in the sixty-three low-LDL cases. The prevalence of FH in Han-Chinese stroke patients was 5.0%, and was 10.3% in those with a higher LDL-C level. We identified six carriers, who had higher percentages of large vessel stroke subtype (66.7% vs. 15.4%) and transient ischemic attack (33.3% vs. 3.8%), previous myocardial infarction/stroke history (50.0% vs. 11.5%), statin use (50.0% vs. 11.5%), and increased carotid intima-media thickness (IMT) (0.9-1.2mm vs.0.7-9.0mm) compared with the other hypercholesterolemic patients without pathogenic variants. Ischemic stroke patients carrying FH pathogenic variants seemed to have a higher risk for large artery stroke and transient ischemic attack. The IMT exam could be useful to screen for FH in hypercholesterolemic stroke patients.

Background: Clinical-diffusion mismatch between stroke severity and diffusion-weighted imaging lesion volume seems to identify stroke patients with penumbra. However, urgent magnetic resonance imaging is sometimes inaccessible or contraindicated. Thus, we hypothesized that using brain computed tomography (CT) to determine a baseline "clinical-CT mismatch" may also predict the responses to thrombolytic therapy., Methods: Brain CT lesions were measured using the Alberta Stroke Program Early CT Score (ASPECTS). A total of 104 patients were included: 79 patients with a baseline National Institutes of Health Stroke Scale (NIHSS) score ≥ 8 and a CT-ASPECTS ≥ 9 who were defined as clinical-CT mismatch-positive (P group) and 25 patients with an NIHSS score ≥ 8 and a CT-ASPECTS < 9 who were defined as clinical-CT mismatch-negative (the N group). We compared their clinical outcomes, including early neurological improvement (ENI), early neurological deterioration (END), delta NIHSS score (admission NIHSS-baseline NIHSS score), symptomatic intracranial hemorrhage (sICH), mortality, and favorable outcome at 3 months., Results: Patients in the P group had a greater proportion of favorable outcome at 3 months (p = 0.032) and more frequent ENI (p = 0.038) and a greater delta NIHSS score (p = 0.001), as well as a lower proportion of END (p = 0.004) than those in the N group patients. There were no significant differences in the incidence rates of sICH and mortality between the two groups., Conclusions: Clinical-CT mismatch may be able to predict which patients would benefit from intravenous thrombolysis., Competing Interests: NO authors have competing interests.

Background: Endovascular thrombectomy (EVT) has become the standard treatment for acute ischemic stroke with large vessel occlusion. Atrial fibrillation (AF) is one of the major causes. However, the impact of AF on the treatment has not yet been clearly discussed. This study is to evaluate the influence of AF on the outcomes of EVT in patients with acute ischemic stroke., Methods: Data from our Stroke Registry Database from April 2015 to July 2018 were reviewed. Technical efficacy, functional, and safety outcomes were reported and compared between patients with and without AF. A multivariate logistic regression model was performed to identify the predictors of the good functional outcome., Results: We reviewed 83 eligible patients receiving EVT. Patients (51.8%) were eventually found to have AF. The substantial reperfusion rate (modified thrombolysis in cerebral infarction 2b-3) was 72.1% and 55.0% in patients with and without AF, respectively, inclusive of a learning curve (p = 0.12). The good functional outcome (90-day modified Rankin scale: 0 to 2) rate was 55.8% and 17.5% in patients with and without AF, respectively (p < 0.01). A multivariable logistic regression analysis showed that age <70 years, the substantial reperfusion, and the presence of AF were three significant predictors for a good functional outcome., Conclusion: Our study showed that patients with AF responded significantly better to EVT than those without AF did. Intracranial atherosclerotic diseases in patients without AF which were especially refractory to EVT may contribute to the difference of the functional outcomes between the two groups.

Background . Recovery of upper limb function post-stroke can be partly predicted by initial motor function, but the mechanisms underpinning these improvements have yet to be determined. Here, we sought to identify neural correlates of post-stroke recovery using longitudinal magnetoencephalography (MEG) assessments in subacute stroke survivors. Methods . First-ever, subcortical ischemic stroke survivors with unilateral mild to moderate hand paresis were evaluated at 3, 5, and 12 weeks after stroke using a finger-lifting task in the MEG. Cortical activity patterns in the β-band (16-30 Hz) were compared with matched healthy controls. Results. All stroke survivors (n=22; 17 males) had improvements in action research arm test (ARAT) and Fugl-Meyer upper extremity (FM-UE) scores between 3 and 12 weeks. At 3 weeks post-stroke the peak amplitudes of the movement-related ipsilesional β-band event-related desynchronization (β-ERD) and synchronization (β-ERS) in primary motor cortex (M1) were significantly lower than the healthy controls (p<0.001) and were correlated with both the FM-UE and ARAT scores (r=0.51-0.69, p<0.017). The decreased β-ERS peak amplitudes were observed both in paretic and non-paretic hand movement particularly at 3 weeks post-stroke, suggesting a generalized disinhibition status. The peak amplitudes of ipsilesional β-ERS at week 3 post-stroke correlated with the FM-UE score at 12 weeks (r=0.54, p=0.03) but no longer significant when controlling for the FM-UE score at 3 weeks post-stroke. Conclusions. Although early β-band activity does not independently predict outcome at 3 months after stroke, it mirrors functional changes, giving a potential insight into the mechanisms underpinning recovery of motor function in subacute stroke.

Background: The triglyceride-glucose (TyG) index has recently been proposed as a reliable marker of insulin resistance. There is insufficient evidence to verify that the TyG index is correlated with functional outcomes and hemorrhagic transformation and in patients with stroke treated with intravenous thrombolysis (IVT). Methods: We designed a multicenter cohort study, which enrolled patients with acute ischemic stroke treated with IVT between December 2004 and December 2016. The TyG index was divided into tertiles and calculated on a continuous scale. Unfavorable functional outcomes were defined by the modified Rankin Scale of 3–6 at 90 days and the incident rates of symptomatic intracranial hemorrhage (SICH) within 36 h of IVT onset were surveyed. Stroke severity was defined as mild (4–8), moderate (9–15), or high (≥16) based on the National Institutes of Health Stroke Scale (NIHSS) scores. Results: Among 914 enrolled patients, the tertiles of the TyG index were 8.48 for T1, 8.48–9.04 for T2, and 9.04 for T3. T3 showed an increased risk of unfavorable functional outcomes at 90 days [odds ratio (OR): 1.76; P = 0.0132]. The TyG index was significantly associated with unfavorable functional outcomes at 90 days (OR: 1.32; P = 0.0431 per unit increase). No association was found between the TyG index and SICH. These findings were applicable for T3 with stroke of moderate (OR, 2.35; P = 0.0465) and high severity (OR: 2.57, P = 0.0440) patients with stroke. Conclusion: This study supports the strong association between the increased TyG index and increased unfavorable functional outcomes at 90 days in patients with acute ischemic stroke treated with IVT. These findings were found to be robust in patients with moderate and high stroke severity. [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety of intravenous alteplase administered 34. 5 h after acute ischemic stroke have been demonstrated. However, whether responses differ between low-dose and standard-dose alteplase during this time window and whether certain subgroups benefit more remain unknown. Patients and Methods: The current analysis was based on a multicenter matched-cohort study conducted in Taiwan. The treatment group comprised 378 patients receiving intravenous alteplase 34.5 h after stroke onset, and the control group comprised 378 age- and sex-matched patients who did not receive alteplase treatment during the same period. Standard- and low-dose alteplase was administered to patients at the physician's discretion. Results: Overall, patients receiving alteplase exhibited more favorable outcomes than did controls [34.0 vs. 22.7%; odds ratio (OR): 1.75, 95% confidence interval (CI): 1.27–1.42], and the effectiveness was consistent in all subgroups. Although patients in the standard-dose group (n = 182) were younger than those in the low-dose (n = 192) group, the proportions of patients with favorable outcomes (36.3 vs. 31.8%; OR: 1.22, 95% CI: 0.80–1.88) and symptomatic hemorrhage (2.8 vs 4.2%; OR: 0.65, 95% CI: 0.21–2.02) were consistently comparable in a covariate-adjusted model and an age-matched cohort. In the subgroup analysis, patients with cardioembolism, atrial fibrillation, and hypercholesterolemia were more likely to achieve favorable outcomes after receiving standard-dose than low-dose alteplase. Conclusion: In the 34.5-h time window, the effectiveness and safety of standard-dose and low-dose alteplase may be comparable. A standard dose may be selected for patients with cardioembolism, atrial fibrillation, or hypercholesterolemia. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke triggers inflammatory responses and oxidative stress in the brain, and microglia polarization affects the degree of neuroinflammation. It has been reported that the inhibition of soluble epoxide hydrolase (sEH) activity protects brain tissue. However, the anti-inflammatory and antioxidative effects of sEH inhibition in the ischemic brain are not fully understood. This study aimed to investigate the effects of a selective sEH inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), after ischemic stroke. Methods: Adult male rats with middle cerebral artery occlusion (MCAO) were administered with AUDA or a vehicle. Behavioral outcome, infarct volume, microglia polarization, and gene expression were assessed. Results: Rats treated with AUDA showed better behavioral outcomes and smaller infarct volumes after MCAO. After AUDA treatment, a reduction of M1 microglia and an increase of M2 microglia occurred at the ischemic cortex of rats. Additionally, there was an increase in the mRNA expressions of antioxidant enzymes and anti-inflammatory interleukin-10, and pro-inflammatory mediators were decreased after AUDA administration. Heme oxygenase-1 was mainly expressed by neurons, and AUDA was found to improve the survival of neurons. Conclusion: The results of this study provided novel and significant insights into how AUDA can improve outcomes and modulate inflammation and oxidative stress after ischemic stroke. [ABSTRACT FROM AUTHOR]

Aspirin, clopidogrel, stroke, intravenous thrombolysis, intracranial hemorrhage Keywords: aspirin; clopidogrel; stroke; intracranial hemorrhage; intravenous thrombolysis EN aspirin clopidogrel stroke intracranial hemorrhage intravenous thrombolysis 1 2 2 09/21/21 20210917 NES 210917 In the published article, there were errors in affiliations 1-5. Instead of "1 School of Public Health, College of Public Health, Taipei, Taiwan, 2 Beijing Tiantan Hospital, Capital Medical University, Beijing, China, 3 Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China, 4 Department of Neurology, Taipei Medical University-Shaung Ho Hospital, Taipei, Taiwan, 5 Department of Health Care Administration, Chung-Hwa University of Medical Technology, Tainan, Taiwan" it should be "1 School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan, 2 Department of Critical Care Medicine, Taipei Medical University Hospital, Taipei, Taiwan, 3 Department of Clinical Pathology, Taipei Medical University, Taipei, Taiwan, 4 Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China, 5 Department of Neurology, Taipei Medical University-Shaung Ho Hospital, Taipei, Taiwan.". [Extracted from the article]

Ischemic stroke is the most common type of cerebrovascular event and is responsible for approximately 85% of all strokes in Taiwan. Neurons contain high concentrations of polyamines, which are prone to various pathological states in the brain and are perturbed after cerebral ischemia. Acrolein, an α,β-unsaturated aldehyde, has been suggested as the primary culprit of neuronal damage in stroke patients. However, the mechanism by which acrolein induces neuronal damage during ischemic stroke is not clear. Urinary 3-hydroxypropyl mercapturic acid (3-HPMA), an acrolein-glutathione (GSH) metabolite, plasma acrolein-protein conjugates (Acr-PC) and plasma GSH levels were analyzed to correlate disease severity and prognosis of stroke patients compared with control subjects. In vivo middle cerebral artery occlusion (MCAO) animal models and an in vitro oxygen glucose deprivation (OGD) stroke model were used to investigate the mechanisms of acrolein-induced neuronal damage. A deregulated acrolein metabolism, including significantly increased plasma Acr-PC levels, decreased urinary 3-HPMA levels and decreased plasma GSH levels, was found in stroke patients compared to control subjects. We further observed that acrolein was produced during ischemia resulting in brain damage in in vivo MCAO animal model. The induction of acrolein in neuronal cells during OGD occurred due to the increased expression of spermidine/spermine N1-acetyltransferase (SSAT) by NF-kB pathway activation. In addition, acrolein elicited a vicious cycling of oxidative stress resulting in neurotoxicity. Finally, N -acetylcysteine effectively prevented OGD-induced neurotoxicity by scavenging acrolein. Overall, our current results demonstrate that acrolein is a culprit of neuronal damage through GSH depletion in stroke patients. The mechanism underlying the role of acrolein in stroke-related neuronal damage occurs through SSAT-induced polyamine oxidation by NF-kB pathway activation. These results provide a novel mechanism of neurotoxicity in stroke patients, aid in the development of neutralizing or preventive measures, and further our understanding of neural protection. Unlabelled Image • A deregulated acrolein metabolism is found in stroke patients. • Acrolein is produced resulting in brain damage in MCAO animal model. • Acrolein occurs through SSAT-induced polyamine oxidation by NF-kB pathway. • Acrolein elicits a vicious cycling of oxidative stress resulting in neurotoxicity. • N -acetylcysteine prevents OGD-induced neurotoxicity by scavenging acrolein. [ABSTRACT FROM AUTHOR]

Abstract Background and purpose The optimal dose of alteplase for acute ischemic stroke among geriatric patients is unclear. We aimed to assess the efficacy and safety of a low-dose (0.6 mg/kg) and standard-dose (0.9 mg/kg) alteplase for varying severity of Asian geriatric stroke patients. Methods The favorable functional outcome on day 90 after stroke onset, and the symptomatic intracranial hemorrhage (SICH) rate following 24–36 h of intravenous alteplase were measured. The baseline NIHSS of 4–8, 9–13, ≥14 were defined as mild, moderate, and high severity, respectively. Results Totally, 249 geriatric patients treated with low-dose (n = 108) and standard-dose (n = 141) alteplase. Compared to standard-dose alteplase, low-dose alteplase had decrease in favorable functional outcome (22.2% versus 34.8%), and no difference in SICH rates was observed. For mild severity patients, the mortality was significantly increased with standard-dose alteplase (the NNT/NNH = 22.9/8.0 for mild severity, the NNT/ NNH = 15.0/14.7 for moderate severity, and the NNT/NNH = 13.5/19.6 for high severity). Conclusions Standard-dose and low-dose alteplase were comparable in reducing major disability, but low-dose alteplase for mild stroke showed much reduced mortality on day 90 for octogenarians. Highlights • Totally, 249 geriatric stroke patients treated with low-dose of 0.6 mg/kg (n =108) and standard-dose (n =141) alteplase. • The stroke severity was defined by NIHSS of 4–8, 9–13, and ≥14 as mild (n =53), moderate (n =64), and high severity (n =128). • For mild severity, the low-dose group had much reduced mortality. The NNT (mRS 0–2) and NNH (mRS 6) were 22.9 and 8.0. • For moderate and high severity patients, the efficacy and safety between the low- and standard-dose groups were comparable. • The NNT/NNH was 15.0/14.7 for moderate severity, and was 13.5/ 19.6 for high severity. [ABSTRACT FROM AUTHOR]