Comparison of the safety and efficacy of Neuroform Atlas stent deployed via Gateway balloon catheter and microcatheter for the treatment of intracranial stenosis.

OBJECTIVE: This study aimed to compare the safety and efficacy of the Atlas stent released by the Gateway catheter and microcatheter in the treatment of intracranial stenosis (IS). METHODS: The primary efficacy and safety outcomes were the in-stent restenosis (ISR) rate and post-procedural stroke or death within one month. RESULTS: Atlas stents were deployed using the Gateway catheter and microcatheter in 19 (57.6 %) and 14 (42.4 %) procedures, respectively. Follow-up imaging data were available for 26 patients; the incidence of ISR was 15.4 %, and the ISR rate was higher, though not significantly, in the microcatheter group than in the Gateway group (30.0% vs. 6.25 %, P = .39). Clinical follow-up data were available for 30 patients; the post-procedural stroke rate was 3.3 % within one month and 13.3 % from one month to one year. The post-procedural stroke rate within one month was higher, though not significantly, in the microcatheter group than in the Gateway group (7.7% vs. 0 %, P = .43). The Gateway group had a significantly lower rate of post-procedural stroke in the same territory than that of the microcatheter group (0% vs. 30.8 %, P = .026). A higher incidence of residual stenosis <30 % was found in the non-ISR group than in the ISR group (72.2% vs. 0 %, P = .014). CONCLUSIONS: This study provides preliminary evidence that the Atlas stent is safe and effective for IS treatment. The use of the Gateway catheter to deliver the Atlas stent appears to be safer than using microcatheter. The incidence of ISR may be related to the degree of the residual stenosis.

Arm-only combined transarterial and transvenous access for neurointerventional procedures: a double-center retrospective study.

OBJECTIVE: This study aims to share our experience with the arm-only combined transarterial and transvenous access approach for neurointerventional procedures and evaluate its efficacy and safety. METHODS: The arm-only combined transarterial and transvenous access approach was performed using the right/bilateral proximal radial arteries and the right forearm superficial vein system, guided by ultrasonic guidance. Arterial access closure was achieved using a transradial band radial compression device, while manual compression was utilized for venous approach closure. RESULTS: Thirteen procedures were successfully performed using the arm-only combined transarterial and transvenous access approach, yielding favorable outcomes. The procedures included dural arteriovenous fistula embolization (seven cases), cerebral arteriovenous malformation embolization (four cases), venous sinus thrombosis catheter-directed thrombolysis and intravenous thrombectomy (one case), and cerebral venous sinus stenosis manometry (one case). All procedures were uneventful, allowing patients to ambulate on the same day. At discharge, all patients exhibited modified Rankin scores of 0-2, without any access site or perioperative complications. CONCLUSION: This double-center study preliminarily demonstrates the feasibility and safety of arm-only combined transarterial and transvenous access applied in neurointerventional procedures for complicated cerebrovascular diseases. The proximal radial artery and forearm superficial vein are recommended as the primary access sites. Unobstructed compression is strongly recommended for radial approach closure. ADVANCES IN KNOWLEDGE: This study aimed to add evidence and experience on the arm-only combined transarterial and transvenous access, as a new approach, for neurointerventional treatment that required arteriovenous approaches.

Serum inflammatory cell adhesion molecules predict malignant cerebral edema and clinical outcome early after mechanical thrombectomy in stroke.

BACKGROUND: Early prediction of life-threatening malignant cerebral edema (MCE) after mechanical thrombectomy (MT) is of clinical importance. Although inflammatory cell adhesion molecules (CAMs) and anti-inflammation factor Kruppel-like transcription factor (KLF) 4 are induced after acute ischemic stroke (AIS), the relationship between expressions of these molecules after MT and MCE as well as outcome in AIS patients have rarely been explored. METHODS: We retrospectively reviewed the data of all AIS patients with large-vessel occlusion in anterior circulation who underwent MT from our stroke centers. The serum levels of CAMs and KLF4 were determined at 12 h after MT. MCE was assessed on follow-up head computed tomography within 5 days after MT. RESULTS: Of 91 included patients, 18 (19.8 %) patients experienced MCE. Patients with MCE were more likely to have higher levels of E-selectin and inter-cellular adhesion molecule 1 (ICAM-1) than those without MCE (P < 0.05). More specifically, elevated E-selectin, but not of vascular cell adhesion molecule 1 (VCAM-1), ICAM-1 and KLF4, was significantly associated with MCE after adjusting for hypertension, admission NIHSS, Alberta Stroke Program Early CT Scores, serum glucose, collateral circulation and onset to recanalization time respectively (P < 0.05). ROC curve suggested that E-selectin had considerable discrimination to predict MCE (AUC=0.7, 95 % CI: 0.55-0.83). Moreover, after adjusting by confounders, serum levels of E-selectin and ICAM-1 were independently associated with 3-month outcome in AIS patients after MT (both P < 0.05). CONCLUSIONS: These data indicate that of three CAMs, serum E-selectin level early after MT is the best predictor for MCE and outcome in AIS.

Progressive crushing 40Ar/39Ar dating of a gold-bearing quartz vein from the Liaotun Carlin-type gold deposit, Guangxi, southern China.

Carlin-type gold deposits are among the largest hydrothermal gold deposits in the world. However, direct dating the metallogenic age of these deposits is difficult, because not all deposits provide material suitable for conventional radiometric methods. Syn-mineralization stage quartz veins from these deposits usually contain abundant fluid inclusions, which allow fluid inclusion 40Ar/39Ar dating. In this study, progressive crushing 40Ar/39Ar dating has been performed on a gold-bearing quartz vein from the Liaotun Carlin-type gold deposit in northwestern Guangxi, China. Argon isotopes liberated from the later steps yielded an isochron age of 200.7 ± 2.1 Ma. We infer that Ar-bearing gas was extracted from the primary fluid inclusions, and that the age of ca. 200.7 Ma reflects the timing of gold mineralization. The initial 40Ar/36Ar ratio corresponding to the isochron is 298.0 ± 4.3, which is statistically indistinguishable from the value for air, indicating that the ore-forming fluids probably mainly derived from gravitational pressure flow in the basin of air-saturated water. Our preliminary study shows the feasibility and great potential of 40Ar/39Ar dating of gases from fluid inclusions by progressive crushing of quartz veins to date the mineralization age and decipher the fluid origins of Carlin-type gold deposits.

Upregulation of circ-FBL promotes myogenic proliferation in myasthenia gravis by regulation of miR-133/PAX7.

Myasthenia gravis (MG) is a disease involving neuromuscular transmission that causes fatigue of skeletal muscles and fluctuating weakness. It has been shown that impairment of myogenic differentiation and myofiber maturation may be the underlying cause of MG. In this study, we detected the abnormal expression of circular RNA (circRNA) using next-generation sequencing in patients with MG. We then investigated the regulatory mechanism and the relationship among circRNA, microRNA, and messenger RNA using quantitative reverse-transcription polymerase chain reaction, bioinformatics analysis, and luciferase report analysis. The expression of inflammatory cytokines and regulatory T lymphocytes was shown to be increased. Circ-FBL was significantly increased in MG patients. Bioinformatics and luciferase report analyses confirmed that miR-133 and PAX7 were the downstream targets of circ-FBL. Overexpression of circ-FBL promoted myoblast proliferation by regulation of miR-133/PAX7. Taken together, our study showed that upregulation of circ-FBL promoted myogenic proliferation in patients with MG by regulating miR-133/PAX7.

Characteristics and prognosis of acute basilar artery occlusion in minor to moderate stroke and severe stroke after endovascular treatment: A multicenter retrospective study.

OBJECTIVE: We aimed to investigate characteristics and outcomes of patients receiving mechanical thrombectomy (MT) between minor to moderate stroke and severe stroke caused by acute basilar artery occlusion (BAO). METHODS: We retrospectively reviewed the data of all patients with BAO who underwent MT from three stroke centers between January 2016 and January 2020. The patients were dichotomized as minor to moderate or severe stroke group according to their admission National Institutes of Health Stroke Scale (NIHSS) score <21and ≥21. Patient characteristics, imaging findings, and outcomes were compared between the two groups. RESULTS: A total of 72 patients were included in this study. The posterior circulation Alberta Stroke Program Early CT Score (PC-ASPECTS) in the minor to moderate stroke patients were significantly higher than that of patients with severe stroke (P = 0.013). The good posterior circulation collateral scores (PC-CS) (6-10) were more commonly found in patients with minor to moderate stroke than in patients with severe stroke (58.14 % vs 10.34 %,P < 0.001). There were similar rates of successful recanalization between the two groups. Patients with minor to moderate stroke had a higher rate of favorable outcomes (mRS score 0-2, 60.47 % vs 20.69 %, P = 0.002) and a lower rate of periprocedural complications (4.65 % vs 31.03 %, P = 0.005) and mortality (4.65 % vs 24.14 %, P = 0.026) at 3 months after MT compared with the patients with severe stroke. CONCLUSIONS: Acute BAO patients with minor to moderate stroke had better posterior circulation collateral and had better outcomes after MT than those patients with severe stroke.

Exosomes Derived From CircAkap7-Modified Adipose-Derived Mesenchymal Stem Cells Protect Against Cerebral Ischemic Injury.

BACKGROUND: Cerebral ischemic injury is a complicated pathological process. Adipose-derived stromal cells (ADSCs) have been used as a therapeutic strategy, with their therapeutic effects chiefly attributed to paracrine action rather than trans-differentiation. Studies have shown that circAkap7 was found to be downregulated in a mouse model of transient middle cerebral artery occlusion (tMCAO). METHODS: To explore whether exosomes derived from circAkap7-modified ADSCs (exo-circAkap7) have therapeutic effects on cerebral ischemic injury, a mouse model of tMCAO, as well as an in vitro model of oxygen and glucose deprivation-reoxygenation (OGD-R) in primary astrocytes, were used. RESULTS: Results showed that treatment with exo-circAkap7 protected against tMCAO in mice, and in vitro experiments confirmed that co-culture with exo-circAkap7 attenuated OGD-R-induced cellular injury by absorbing miR-155-5p, promoting ATG12-mediated autophagy, and inhibiting NRF2-mediated oxidative stress. CONCLUSION: We demonstrate here that exo-circAkap7 protected against cerebral ischemic injury by promoting autophagy and ameliorating oxidative stress.

Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting M2 Microglial/Macrophage Polarization.

BACKGROUND/AIMS: Recent studies have indicated that exosomes secreted from adipose-derived stem cells (ADSCs) have important effects in the treatment of ischemic injury. However, the treatment mechanism is unclear. This study aimed to investigate whether ADSC-derived exosomes enriched with microRNA (miR)-30d-5p have a protective effect on acute ischemic stroke (AIS). METHODS: In the current study, inflammatory factors and miR-30d-5p expression were assessed in 70 subjects with AIS and 35 healthy controls. Exosomes were characterized by transmission electron microscopy and further examined using nanoparticle tracking analyses. A rat model of AIS and an in vitro model of oxygen- and glucose-deprived (OGD) primary microglia were established to study the protective mechanism of exosomes from miR-30d-5p-overexpressing ADSCs in ischemia-induced nerve injury. RESULTS: The results showed that following AIS, the expression of inflammatory cytokines increased, while the anti-inflammatory cytokines IL-4, IL-10, and miR-30d-5p decreased both in patients and in animal models. Moreover, in vitro studies demonstrated that suppression of autophagy significantly reduced the OGD-induced inflammatory response. In addition, exosome treatment was more effective in suppressing the inflammatory response by reversing OGD-induced and autophagy-mediated microglial polarization to M1. Furthermore, in vivo studies showed that exosomes derived from ADSCs significantly decreased the cerebral injury area of infarction by suppressing autophagy and promoting M2 microglia/macrophage polarization. CONCLUSIONS: Our results suggest that miR-30d-5p-enhanced ADSC-derived exosomes prevent cerebral injury by inhibiting autophagy-mediated microglial polarization to M1.

Downregulation of circ_008018 protects against cerebral ischemia-reperfusion injury by targeting miR-99a.

Circular RNAs (circRNAs) are highly expressed in eukaryotic cells and regulate physiological and pathophysiological processes. However, the role of circRNAs in cerebral ischemia-reperfusion (I/R) injury remains largely unknown. In this study, we found that circ_008018 level was higher in the cortical tissue of mice with middle cerebral artery occlusion as compared to those in the sham group 24 h after reperfusion. Knockdown of circ_008018 attenuated cerebral I/R-induced brain tissue damage and neurological deficits in mice by inducing microRNA miR-99a overexpression. The decreased phosphorylation of Akt and glycogen synthase kinase 3ß caused by I/R was partly reversed by circ_008018 silencing or miR-99a overexpression. Taken together, these results provide new insight into the mechanisms of apoptosis resulting from cerebral I/R injury and suggest that targeted inhibition of circ_008018 can protect against subsequent neurological damage.

Clinical markers of neurodegeneration in Chinese patients with idiopathic rapid eye movement sleep behavior disorder.

OBJECTIVE: It is reported that neurodegenerative markers of Parkinson's disease occur in patients with idiopathic rapid eye movement sleep behavior disorder (idiopathic RBD); however, it has been unknown in Chinese patients. This study aims to provide a detailed understanding of the clinical features of Chinese patients with idiopathic RBD. METHODS: We conducted a series of Parkinson related motor and non-motor assessments in 181 participants including 41 patients with idiopathic RBD, 35 Parkinson's patients without RBD, 42 Parkinson's patients with RBD, and 63 healthy controls. The RBD questionnaire -Hong Kong (RBDQ-HK) was used to confirm clinical RBD symptoms and evaluate the severity. Motor function including Unified Parkinson's disease Rating Scale (UPDRS), alternative tap test, Purdue Pegboard test and Timed Up and Go test, and non-motor functions including olfaction, cognition, and autonomic function were assessed in each group. RESULTS: Motor assessments of UPDRS, Purdue Pegboard, and Timed Up and Go, and the systolic blood pressure (BP) drop in patients with idiopathic RBD were intermediate between controls and Parkinson's patients. However, the alternative tap test and some non- motor functions including olfaction and orthostatic symptoms in idiopathic RBD were impaired as seriously as in Parkinson's disease. No difference was found in urinary and bowel function between idiopathic RBD and controls. In idiopathic RBD, functional impairment was associated with age and the severity of RBD symptoms (p<0.05). In addition, systolic BP drops closely correlated to motor function and bowel function (p<0.05). CONCLUSIONS: Chinese patients with idiopathic RBD demonstrated an extensive and heterogeneous functional impairment. The association between functional impairment and age and the severity of RBD symptoms needs to be determined in future studies.

Targeting the D1-N-methyl-D-aspartate receptor complex reduces L-dopa-induced dyskinesia in 6-hydroxydopamine-lesioned Parkinson's rats.

L-3,4-dihydroxyphenylalanine (L-dopa) remains the most effective therapy for Parkinson's disease (PD), but its long-term administration is associated with the development of debilitating motor complications known as L-dopa-induced dyskinesia (LID). Enhanced function of dopamine D1 receptor (D1R) and N-methyl-D-aspartate receptor (NMDAR) is believed to participate in the pathogenesis of LID. Given the existence of physical and functional interactions between D1R and NMDAR, we explored the effects of uncoupling D1R and NMDA GluN1 (GluN1) interaction on LID by using the Tat-conjugated interfering peptide (Tat-D1-t2). In this study, we demonstrated in 6-hydroxydopamine (6-OHDA)-lesioned PD rat model that intrastriatal injection of Tat-D1-t2 alleviated dyskinetic behaviors and downregulated the phosphorylation of DARPP-32 at Thr34 induced by levodopa. Moreover, we also showed intrastriatal administration of Tat-D1-t2 elicited alterations in membranous GluN1 and D1R expression. These findings indicate that D1R/GluN1 complexes may be a molecular target with therapeutic potential for the treatment of dyskinesia in Parkinson's patients.