Search

Background: Angioplasty and stenting have recently become attractive options for cerebral large artery stenosis in China. However, there are limited data on safety and long-term outcomes in Chinese patients having undergone cerebral interventional procedures. To address this need, we set up a common database - the China Interventional Stroke Registry (CISR) - to describe patient characteristics, interventional images, periprocedural complications and long-term clinical outcomes and to determine how adherence to guideline-based treatments in the 'real world' works in China. Methods: Six medical centers have participated since 2004. They entered into an Internet-based database data on demographics, clinical history and angiography of patients undergoing angioplasty with/without stenting in extracranial arteries (carotid, vertebral and subclavian arteries) and/or intracranial arteries (middle cerebral artery, vertebral artery and basilar artery) in China. CISR is a research-funded project. Results: As of October 2012, we have already collected detailed clinical information on 1,356 patients (age: 63.6 ± 10.2 years, male: 1,084, 79.9%). The overall data quality is good. Site data quality control is supported via detailed monthly feedback reports and quarterly data monitoring meetings. Conclusions: The CISR is the first and the largest registry for angioplasty with/without stents in China. The database will provide the characteristics and outcomes of patients and the situation of adherence to guideline-based treatments under 'real-world' conditions in China. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Ferroptosis is a form of non-apoptotic cell death caused by iron-dependent peroxidation of lipids. It contributes to ischemic stroke-induced neuronal damage. Elabela (ELA), a novel endogenous ligand for Apelin receptor (APJ), regulates oxidative stress and exerts a protective role in cardiovascular disease. However, the effect of ELA-APJ axis on cellular ferroptosis in cerebral ischemia/reperfusion (I/R) remains elusive. The present study showed that ELA and APJ were expressed on neurons and increased after cerebral I/R injury. The I/R insult triggered typical molecular and morphological features of neuronal ferroptosis, including iron and MDA accumulation, mitochondrial shrink and membrane rupture, upregulation of positive ferroptosis regulators and downregulation of negative regulators. ELA-32 treatment reduced brain infarction and ameliorated neurobehavioral deficits and cognitive dysfunction. Moreover, ELA-32 administration alleviated neuronal ferroptosis, accompanied by reduced iron deposition, decreased mitochondrial damage, relived lipid peroxidation and glutathione reduction. Such effects of ELA-32 were abolished by AAV-APJ-RNAi or nuclear factor erythroid 2-related factor 2 (NRF2) inhibitor ML385. Mechanistically, ELA was shown to bind to APJ and activate NRF2/ARE anti-oxidative signaling pathway via Gα13. Together, these findings suggested that ELA-APJ axis mitigates neuronal ferroptosis after ischemic stroke and that the ELA-32 peptide may be a putative therapeutic avenue for ischemic stroke. [Display omitted] • Ischemic stroke induces Elabela and APJ expression and neuronal ferroptosis. • Activation of APJ with ELA-32 ameliorates ischemia/reperfusion injury and cognitive dysfunction. • Treatment with ELA-32 reduces neuronal lipid peroxidation and ferroptosis via NRF2/ARE signaling pathway. • Elabela binds to APJ and subsequently triggers NRF2-mediated anti-oxidative response through Gα13. [ABSTRACT FROM AUTHOR]

Background: Vascular angioplasty and stenting of middle cerebral artery (MCA) and basilar artery (BA) stenoses are associated with poor clinical outcomes and high mortality rates thought to be related to the abundance of perforating arteries in those segments. This study explores the use of Solitaire AB as an off-label vascular stent to treat stenoses in the MCA and BA. Methods: Solitaire AB stents were placed during angioplasty and stenting of MCA and BA stenoses in patients at our department between January 2015 and May 2017 with 6-36 months follow-up. Operative results were assessed by follow-up angiography and transcranial doppler after the procedure. Neurologic status was evaluated before and after treatment according to the modified Ranking Scale (mRS). Results: A total of 32 patients were included in the study. Seventeen (53.12%) patients presented with MCA stenosis and 15 (46.87%) with BA stenosis. The 30-day rate of procedure-related complications was 3.1% (1/32). Post-stenting residual stenosis degrees ranged from 0% to 40% (mean 13.44% ± 10.66%). Mean degree of residual stenosis in 26 patients followed up by DSA was 8.64% ± 9.67%. The mRS 0-2 was achieved in all (100%) patients at 6-12 months post-procedure. Conclusions: Our study indicates the off-label use of Solitaire AB for stenting is effective and safe for MCA and BA stenoses with high technical success and low complications. We recommend that lesion-specific therapy with an anatomically fitted stent design enables optimal treatment for intracranial stenosis. [ABSTRACT FROM AUTHOR]

Background: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive treatment for ischemic stroke. Astrocytes regulation has been suggested as one mechanism for rTMS effectiveness. But how rTMS regulates astrocytes remains largely undetermined. There were neurotoxic and neuroprotective phenotypes of astrocytes (also denoted as classically and alternatively activated astrocytes or A1 and A2 astrocytes) pertaining to pro- or anti-inflammatory gene expression. Pro-inflammatory or neurotoxic polarized astrocytes were induced during cerebral ischemic stroke. The present study aimed to investigate the effects of rTMS on astrocytic polarization during cerebral ischemic/reperfusion injury.Methods: Three rTMS protocols were applied to primary astrocytes under normal and oxygen-glucose deprivation/reoxygenation (OGD/R) conditions. Cell survival, proliferation, and phenotypic changes were assessed after 2-day treatment. Astrocytes culture medium (ACM) from control, OGD/R, and OGD/R + rTMS groups were mixed with neuronal medium to culture neurons for 48 h and 7 days, in order to explore the influence on neuronal survival and synaptic plasticity. In vivo, rats were subjected to middle cerebral artery occlusion (MCAO), and received posterior orbital intravenous injection of ACM collected from different groups at reperfusion, and at 3 days post reperfusion. The apoptosis in the ischemic penumbra, infarct volumes, and the modified Neurological Severity Score (mNSS) were evaluated at 1 week after reperfusion, and cognitive functions were evaluated using the Morris Water Maze (MWM) tests. Finally, the 10 Hz rTMS was directly applied to MCAO rats to verify the rTMS effects on astrocytic polarization.Results: Among these three frequencies, the 10 Hz protocol exerted the greatest potential to modulate astrocytic polarization after OGD/R injury. Classically activated and A1 markers were significantly inhibited by rTMS treatment. In OGD/R model, the concentration of pro-inflammatory mediator TNF-α decreased from 57.7 to 23.0 рg/mL, while anti-inflammatory mediator IL-10 increased from 99.0 to 555.1 рg/mL in the ACM after rTMS treatment. The ACM collected from rTMS-treated astrocytes significantly alleviated neuronal apoptosis induced by OGD/R injury, and promoted neuronal plasticity. In MCAO rat model, the ACM collected from rTMS treatment decreased neuronal apoptosis and infarct volumes, and improved cognitive functions. The neurotoxic astrocytes were simultaneously inhibited after rTMS treatment.Conclusion: Inhibition of neurotoxic astrocytic polarization is a potential mechanism for the effectiveness of high-frequency rTMS in cerebral ischemic stroke. [ABSTRACT FROM AUTHOR]

• dMCAO causes WaD in non-ischemic bilateral CC and ipsilateral striatum. • This WaD is recognized with demyelination, APP deposition and neuroglia activation. • Degeneration of contralateral CC is secondary to ipsilateral CC. • No substantial changes are observed in contralateral striatum after dMCAO. Wallerian degeneration (WaD), commonly secondary to cerebral infarction, is the descending damage of fiber tracts with their accompanying myelin sheaths. However, whether this sequential injury can occur in non-ischemic corpus callosum (CC) and striatum in focal cortical ischemic model has not been fully demonstrated. The present study aimed to elucidate detailed histopathologic changes in CC and striatum after acute focal cortical infarction induced by permanent distal middle cerebral artery occlusion (dMCAO) in Sprague–Dawley rat. We found that myelin integrity, myelin-related proteins, MBP and MAG, and NF200-marked neurofilaments were all compromised in non-ischemic white matter regions, bilateral CC and ipsilateral striatum, along with cortical ischemia (all P < 0.05). Electron microscopy showed wide gaps between myelin sheath layers or between axon and myelin, with an abnormal folding of myelin sheath, and enlarged fluid-filled areas. APP accumulations were noted at 24 h post-dMCAO in those non-ischemic regions, and the deposition prolonged until 14 days after cortical ischemia (all P < 0.05). Moreover, in these areas, microglia and astrocytes were robustly and persistently activated in different patterns. No substantial changes were observed in contralateral striatum. In conclusion, our results suggest that WaD may be involved in non-ischemic CC and striatum after focal cortical infarction, accompanied by APP aggregation and neuroglia initiation forming the glial scar. [ABSTRACT FROM AUTHOR]

Background: Lesion patterns may predict prognosis after acute ischemic stroke within the middle cerebral artery (MCA) territory; yet it remains unclear whether such imaging prognostic factors are related to patient outcome after intravenous thrombolysis. Aims: The aim of this study is to investigate the clinical outcome after intravenous thrombolysis in acute MCA ischemic strokes with respect to diffusion-weighted imaging (DWI) lesion patterns. Methods: Consecutive acute ischemic stroke cases of the MCA territory treated over a 7-year period were retrospectively analyzed. All acute MCA stroke patients underwent a MRI scan before intravenous thrombolytic therapy was included. DWI lesions were divided into 6 patterns (territorial, other cortical, small superficial, internal border zone, small deep, and other deep infarcts). Lesion volumes were measured by dedicated imaging processing software. Favorable outcome was defined as modified Rankin scale (mRS) of 0-2 at 90 days. Results: Among the 172 patients included in our study, 75 (43.6%) were observed to have territorial infarct patterns or other deep infarct patterns. These patients also had higher baseline NIHSS score (p < 0.001), a higher proportion of large cerebral artery occlusions (p < 0.001) and larger infarct volume (p < 0.001). Favorable outcome (mRS 0-2) was achieved in 89 patients (51.7%). After multivariable analysis, groups with specific lesion patterns, including territorial infarct and other deep infarct pattern, were independently associated with favorable outcome (OR 0.40; 95% CI 0.16-0.99; p = 0.047). Conclusions: Specific lesion patterns predict differential outcome after intravenous thrombolysis therapy in acute MCA stroke patients. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: We aim to investigate the correlation between presence of anterior temporal artery (ATA), the first major branch of middle cerebral artery (MCA), on conventional angiography and clinical outcome in patients with acute atherosclerotic M1-MCA occlusion. Methods: Consecutive patients with acute atherosclerotic M1-MCA occlusion from Nanjing Stroke Registry Program (NSRP) between January 2007 and December 2012 were included in this study. All patients underwent MRI followed by conventional angiography. From their data, we analyzed baseline characteristics, infarction patterns, DWI-ASPECTS, and collateral circulation. The correlation of ATA presence and good clinical outcome, modified Rankin Scale (mRS) score ≤2, at 3 months was also calculated. Results: In 98 patients meeting entry criteria, the presence of ATA was found in 44 patients. Patients with ATA present were found to have less hypertension ( p = 0.042), lower baseline National Institutes of Health Stroke Scale (NIHSS) ( p = 0.043), more small infarcts in perforating artery territory ( p = 0.013), and a higher number of DWI-ASPECTS ≥7 ( p = 0.034). Binary logistic regression analysis showed an adjusted odds ratio of 4.45 for a good outcome in patients with ATA presence (95 % CI 1.52 to 13.03, p = 0.007). Conclusion: The presence of ATA can be used as a predictor of good outcome in patients with acute atherosclerotic M1-MCA occlusion. [ABSTRACT FROM AUTHOR]

ABSTRACT BACKGROUND AND PURPOSE There are some controversial results on the relationship between cerebral atherosclerosis and leukoaraiosis in the published papers, where cerebral atherosclerosis was often evaluated by ultrasonography, CTA or MRA. We analyzed data in which patients underwent both MRI and DSA to explore the above relationship in the aged people. METHODS Three hundred and thirty-three patients were enrolled in the study from the Nanjing Stroke Registry. They underwent both cerebral DSA and MRI. Age, sex, and vascular risk factors were collected. Atherosclerosis was scored from grade 0 to 4. Leukoaraiosis was scored from grade 0 to 3. RESULTS Cerebral artery stenosis was not correlated with the presence of leukoaraiosis. There were no correlations between the number of cerebral moderately or more severely stenotic arteries and the severity of leukoaraiosis in periventricular, deep, or whole white matter ( P = .747, .268, and .608, respectively). Old age (odds ratio = 1.103, P = .027) and hypertension (odds ratio = 2.748, P = .003) were correlated with leukoaraiosis in the periventricular white matter. Old age (odds ratio = 1.073, P = .031) and prior stroke (odds ratio = 2.678, P = .002) were correlated with leukoaraiosis in the deep white matter. CONCLUSIONS No apparent correlation exists between cerebral artery stenosis and the presence and severity of leukoaraiosis. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the changes and the molecular mechanisms of cerebral vascular damage and tested the therapeutic effects of Niaspan in type-1 streptozotocin induced diabetic (T1DM) rats after stroke. T1DM-rats were subjected to transient middle cerebral artery occlusion (MCAo) and treated without or with Niaspan. Non-streptozotocin rats (WT) were also subjected to MCAo. Functional outcome, blood–brain-barrier (BBB) leakage, brain hemorrhage, immunostaining, and rat brain microvascular endothelial cell (RBEC) culture were performed. Compared to WT-MCAo-rats, T1DM-MCAo-rats did not show an increase lesion volume, but exhibited significantly increased brain hemorrhage, BBB leakage and vascular damage as well as decreased functional outcome after stroke. Niaspan treatment of stroke in T1DM-MCAo-rats significantly attenuated BBB damage, promoted vascular remodeling and improved functional outcome after stroke. T1DM-MCAo-rats exhibited significantly increased Angiopoietin 2 (Ang2) expression, but decreased Ang1 expression in the ischemic brain compared to WT-MCAo-rats. Niaspan treatment attenuated Ang2, but increased Ang1 expression in the ischemic brain in T1DM-MCAo-rats. In vitro data show that the capillary-like tube formation in the WT-RBECs marginally increased compared to T1DM-RBEC. Niaspan and Ang1 treatment significantly increased tube formation compared to non-treatment control. Inhibition of Ang1 attenuated Niacin-induced tube formation in T1DM-RBECs. Niaspan treatment of stroke in T1DM-rats promotes vascular remodeling and improves functional outcome. The Ang1/Ang2 pathway may contribute to Niaspan induced brain plasticity. Niaspan warrants further investigation as a therapeutic agent for the treatment of stroke in diabetics. [Copyright &y& Elsevier]

Abstract: Objective: This study was aimed to evaluate relationship between hyperintense vessels (HV) on fluid-attenuated inversion recovery (FLAIR) and artery steno-occlusion related intracerebral collaterals. Materials and methods: A total of 233 patients with 260 atherosclerotic lesions in the M1 segment of the middle cerebral artery (MCA) were examined with FLAIR and digital subtraction angiography (DSA). HV were graded as 0, 1, 2 and 3 by its distributions in the MCA territory. Grade 0 indicated no HV; Grade 1 indicated the HV limited in Sylvian fissure; Grade 2 indicated the HV limited in Sylvian fissure and the temporal-occipital junction; Grade 3 indicated the HV extended to frontal-parietal lobes. Collateral blood flows were classified by DSA results. The relationship between HV grades and patterns of collateral flows was analyzed. Results: HV were observed in 76 out of 260 hemispheres. For patients with Grade 1 HV, most of their collateral flows (80.8%) were antegrade; for patients with Grade 2, the retrograde leptomeningeal flows were commonly manifested as anterior cerebral artery to MCA (75%); for patients with Grade 3 HV, most of the retrograde leptomeningeal flows were manifested as posterior cerebral artery to MCA (81.8%). As the grade HV increased, the frequency of retrograde leptomeningeal collateral from ACA to MCA decreased (100% to 75% and to 18.2%), and increased (0% to 25% and to 81.8%) for the retrograde leptomeningeal collateral via PCA to MCA (P <0.001). Conclusions: The HV could assess non-invasively intracerebral collaterals in patients with steno-occlusive lesions of M1 segment of MCA. [Copyright &y& Elsevier]

Rationale Many recent studies suggest that the kallikrein-kinin system play a protective role in the impairment of vascular smooth muscle cells and vascular endothelial cell. Aims The study aims to determine whether tissue kallikrein is efficacy for preventing the long-term in-stent restenosis after stenting of symptomatic atherosclerotic stenosis of the middle cerebral artery M1 segment. Design This is a Phase II, randomized, single-blinded, controlled trial. In line with SAMMPRIS stenting indications, patients ( n = 90) with the symptomatic the middle cerebral artery M1 segment stenosis ≥70% and successfully treated with stent will be enrolled. Eligible patients will be randomized using computer generated numbers, and allocated to receive tissue kallikrein treatment or not. Patients in tissue kallikrein treatment group will be prescribed with intravenous infusion of tissue kallikrein (0·15 PNAU/d, dissolved in 100 ml saline) for 7 days after stenting and then oral administration of pancreatic kallikrein enteric-coated tablet (240 U, 3/d) to the end of study. As the foundation treatment, all the enrolled patients will receive aspirin (100 mg/d), clopidogrel (75 mg/d), and atorvastatin (20 mg/d) for the first 6 months and continue with the combination of aspirin and atorvastatin at the previous dosage. Study outcomes Patients will be evaluated at 1, 6 and 12 months after stenting. The primary outcomes are the in-stent restenosis rate, new stroke or aggravation of the previous ischemic stroke ipsilateral to the severe stenotic artery. Secondary outcomes include stroke of other artery territories, myocardial infarction and vascular death. Modification of stroke knowledge, exercise and diet habit, smoking cessation and available laboratory data will also be recorded. Conclusion As our pilot study, tissue kallikrein would be expected to prevent the long-term in-stent restenosis after stenting of the symptomatic middle cerebral artery dramatically. [ABSTRACT FROM AUTHOR]

Background: Functions of astrocytes in the rehabilitation after ischemic stroke, especially their impacts on inflammatory processes, remain controversial. This study uncovered two phenotypes of astrocytes, of which one was helpful, and the other harmful to anoxic neurons after brain ischemia.Methods: We tested the levels of inflammatory factors including TNF-a, IL-6, IL-10, iNOS, IL-1beta, and CXCL10 in primary astrocytes at 0 h, 6 h, 12 h, 24 h, and 48 h after OGD, grouped the hypoxia astrocytes into iNOS-positive (iNOS(+)) and iNOS-negative (iNOS(-)) by magnetic bead sorting, and then co-cultured the two groups of cells with OGD-treated neurons for 24 h. We further verified the polarization of astrocytes in vivo by detecting the co-localization of iNOS, GFAP, and Iba-1 on MCAO brain sections. Lentivirus overexpressing LCN2 and LCN2 knockout mice (#024630. JAX, USA) were used to explore the role of LCN2 in the functional polarization of astrocytes. 7.0-T MRI scanning and the modified Neurological Severity Score (mNSS) were used to evaluate the neurological outcomes of the mice.Results: After oxygen-glucose deprivation (OGD), iNOS mRNA expression increased to the peak at 6 h in primary astrocytes, but keep baseline expression in LCN2-knockout astrocytes. In mice with transient middle cerebral artery occlusion (tMCAO), LCN2 was proved necessary for astrocyte classical activation. In LCN2 knockout mice with MCAO, no classically activated astrocytes were detected, and smaller infarct volumes and better neurological functions were observed.Conclusions: The results indicated a novel pattern of astrocyte activation after ischemic stroke and lipocalin-2 (LCN2) plays a key role in polarizing and activating astrocytes. [ABSTRACT FROM AUTHOR]

Objective: New vessels formation (NVF) along the steno‐occlusive middle cerebral artery (MCA) is often observed in digital subtraction angiography (DSA) imaging. In the study, we aim to explore the clinical relevance of NVF in young ischemic stroke patients with isolated middle cerebral artery (MCA) stenosis. Methods: We retrospectively reviewed the digital subtraction angiography (DSA) images of 93 young ischemic stroke patients (age ≤ 45 years old) in our center from January 2006 to June 2016. All the patients were diagnosed with isolated steno‐occlusive middle cerebral artery (MCA) disease.NVF was defined as new vessels formation along the stenotic MCA on anteroposterior DSA projection. The association between NVF and functional outcome was analyzed. Results: The prevalence of NVF was 0 in moderate stenosis, 15.8% in severe stenosis, and 53.7% in MCA occlusions. The presence of NVF had a strong correlation with the severity of MCA stenosis (r = 0.467, p < 0.001). Compared to patients without NVF, patients with NVF were more likely to suffer an unfavorable functional outcome (6.2% vs. 21.4%, p = 0.061) at 3 months. Univariate logistic regression analysis showed that NVF was associated with unfavorable outcome [Odds Ratio (OR) = 4.159, 95% confidence intervals (CI) = (1.072, 16.137), p = 0.039]. Conclusions: This study demonstrated that NVF were associated with poor clinical outcome in young ischemic stroke patients who were diagnosed with isolated steno‐occlusive MCA. New vessels formation was significantly correlated with the severity of MCA stenosis in young ischemic stroke patients with isolated MCA steno‐occlusive disease. In terms of stroke outcome, NVF predicts unfavorable outcome at 3 months after symptom onset. [ABSTRACT FROM AUTHOR]