Bone Morphogenic Protein 9(BMP9)/Growth Differentiation Factor 2(GDF2)modulates mouse adult hippocampal neurogenesis by regulating the survival of early neural progenitors

Adult neurogenesis occurs in two specialized regions of the mammalian brain,the subventricular zone(SVZ)and the subgranular zone(SGZ)of the dentate gyrus(DG).^(1)Adult hippocampal neural stem cells(NSCs),referred to as Type 1 cells represented by radial glia-like cells(RGLs),generate Type 2 cells that are divided into Type 2a and Type 2 b subpopulations,the latter of which give rise to Type 3 cells(neuroblasts).

Movable typing of full-lumen personalized Vein-Chips to model cerebral venous sinus thrombosis

Cerebral venous sinus thrombosis(CVST)is a type of stroke associated with COVID-19 vaccine-induced immune thrombotic thrombocytopenia.The precise etiology of CVST often remains elusive due to the highly heterogeneous nature of its governing mechanisms,specifically,Virchow’s triad that involves altered blood flow,endothelial dysfunction,and hypercoagulability,which varies substantially amongst individuals.Existing diagnostic and monitoring approaches lack the capability to reflect the combination of these patient-specific thrombotic determinants.In response to this challenge,we introduce a Vein-Chip platform that recapitulates the CVST vascular anatomy from magnetic resonance venography and the associated hemodynamic flow profile using the“Chinese Movable Type-like”soft stereolithography technique.The resultant full-lumen personalized Vein-Chips,functionalized with endothelial cells,enable in-vitro thrombosis assays that can elucidate distinct thrombogenic scenarios between normal vascular conditions and those of endothelial dysfunction.The former displayed minimal platelet aggregation and negligible fibrin deposition,while the latter presented significant fibrin extrusion from platelet aggregations.The low-cost movable typing technique further enhances the potential for commercialization and broader utilization of personalized Vein-Chips in surgical labs and at-home monitoring.Future research and development in this direction will pave the way for improved management and prevention of CVST,ultimately benefiting both patients and healthcare systems.

Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk

Wnt signaling plays a major role in regulating cell proliferation and differentiation.The Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical pathway.Many of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling pathways.This crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ processes.Dys-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic lethality.The complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic treatments.However,both stimulatory and inhibitory treatments come with potential risks that need to be addressed.This review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt signaling.It thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+pathway.Further description involved each of its components and their involvement in other cellular processes.Finally,this review explained the various other pathways and processes that crosstalk with Wnt signaling.

A simplified noncryogenic strategy to transport mesenchymal stem cells: Potential applications in cell therapy and regenerative medicine

With the rapid advances in stem cell research and po-tential cell-based therapies,there is an urgent need to develop safe and reliable cell transport strategies.Except for autologous stem cell-based therapies,allogeneic stem cell therapies and ex vivo genetically engineered cell therapies would require safe,efficient,and reliable cell preservation and transport methods.

Endovascular revascularisation of acute tandem vertebrobasilar artery occlusion:seven case series with literature reviews

background The outcome of acute ischaemic stroke due to tandem vertebrobasilar artery occlusion was poor.Endovascular revascularisation may be a positive approach for acute basilar artery occlusion combined with vertebral ostium stenosis or occlusion.We reported seven patients with acute vertebrobasilar tandem occlusion by using angioplasty or stenting for proximal lesion and thrombectomy for distal occlusion.Materials and methods Consecutive patients with acute tandem vertebrobasilar artery occlusion at two centres were included in this study.We retrospectively analysed the clinical,technical and functional outcomes of the patients.results From March 2016 to March 2017,seven patients were included.The mean age and National Institute of Health Stroke Scale score at admission was 57 years and 22,respectively.A reverse approach was used in five patients.The Thrombolysis in Cerebral Infarction score 2b-3 was acquired in all patients.There were no procedural complications.The modified Rankin Scale score was 1-2 for three patients and 4 for one patient at 3 months.Three patients died at 3 months of follow-up.Conclusions Endovascular revascularisation may be feasible for acute tandem vertebrobasilar artery occlusion,and more researches are needed.

Stenting for symptomatic intracranial arterial stenosis in China:1-year outcome of a multicentre registry study

background and purpose A multicentre prospective registry study of individually tailored stenting for a patient with symptomatic intracranial atherosclerotic stenosis(ICAS)combined with poor collaterals in China showed that the short-term safety and efficacy of stenting was acceptable.However,it remained uncertain whether the low event rate could be of a long term.We reported the 1-year outcome of this registry study to evaluate the long-term efficacy of individually tailored stenting for patients with severe symptomatic ICAS combined with poor collaterals.Methods Patients with symptomatic ICAS caused by 70%-99% stenosis located at the intracranial internal carotid,middle cerebral,intracranial vertebral or basilar arteries combined with poor collaterals were enrolled.Balloon-mounted stent or balloon plus self-expanding stent were selected based on the ease of vascular access and lesion morphology determined by the operators.The primary outcome was the rate of 30-day stroke,transient ischaemic attack and death,and 12-month ischaemic stroke within the same vascular territory,haemorrhagic stroke and vascular death after stenting.results From September 2013 to January 2015,300 patients(ages 58.3±9.78 years)were recruited.Among them,159 patients were treated with balloon-mounted stent and 141 with balloon plus self-expanding stent.During the 1-year follow-up,25 patients had a primary end point event.The probability of primary outcome at 1 year was 8.1%(95% CI 5.3% to 11.7%).In 76 patients with digital subtraction angiography follow-up,27.6%(21/76)had re-stenosis≥50% and 18.4%(14/76)had re-stenosis≥70%.No baseline characteristic was associated with the primary outcome.Conclusion The event rate remains low over 1 year of individually tailored stenting for patients with severe symptomatic ICAS combined with poor collaterals.Further randomised trial of comparing individually tailored stenting with best medical therapy is needed.

Acute Ischaemic Stroke Cooperation Group of Endovascular Treatment (ANGEL) registry: study protocol for a prospective, multicentre registry in China

Background and purpose Endovascular treatment could improve functional outcomes and reduce mortality in patients with intracranial large artery occlusion. This registry aims to evaluate the endovascular treatment delivery and to improve endovascular treatment algorithm in clinical practice for patients with stroke in China. Methods and analysis This multicentric, nationwide, prospective registry plans to include 20 stroke centres and recruit 900 consecutive AIS patients with large- artery occlusion under endovascular treatment. This registry will enrol acute large vessel occlusion patients suitable for endovascular treatment and the inclusion and exclusion criteria. In this study, 90 days functional independence (modified Rankin Scale score ≤2) is the primary efficacy endpoint. The procedural efficacy endpoint of this registry is target artery recanalisation defined by modified Thrombolysis in Cerebral Infarction score 2b or 3 after endovascular therapy. Symptomatic intracranial haemorrhage with 24±3 hours after the procedure is the primary safety endpoint of this registry. Ethics and dissemination Beijing Tiantan Hospital’s Ethics committee and all other participating centres approved the protocol and data collection of Acute Ischaemic Stroke Cooperation Group of Endovascular Treatment registry. Each participant or representative had a written informed consent.

Endovascular treatment with or without intravenous alteplase for acute ischaemic stroke due to basilar artery occlusion

Background and purpose It remains controversial if endovascular treatment(EVT)can improve the outcome of patients with acute basilar artery occlusion(BAO).This study aims to compare the functional outcomes between EVT with and without intravenous thrombolysis(IVT)first in patients who had acute ischaemic stroke(AIS)due to BAO.Methods Patients who had AIS with BAO who underwent EVT within 24 hours of onset were enrolled in this multicentre cohort study,and the efficacy and safety were compared between IVT+EVT and direct EVT.The primary outcome was 90-day functional independence.All outcomes were assessed with adjusted OR(aOR)from the multivariable logistic regression.In addition,a meta-analysis was performed on all recently published pivotal studies on functional independence after EVT in patients with BAO.Results Of 310 enrolled patients with BAO,241(78%)were treated with direct EVT and 69(22%)with IVT+EVT.Direct EVT was associated with a worse functional outcome(aOR,0.46(95%CI 0.24 to 0.85),p=0.01).IVT+EVT was associated with a lower percentage of patients who needed≥3 passes of stent retriever(10.14%vs 20.75%).The meta-analysis regression revealed a potential positive correlation between bridging with IVT first and functional independence(r=0.14(95%CI 0.05 to 0.24),p<0.01).Conclusions This study showed that compared with direct EVT,EVT with IVT first was associated with better functional outcomes in patients with BAO treated within 24 hours of onset.The meta-analysis demonstrated similar favourable efficacy of IVT first followed by EVT in patients with BAO.

Perfusion and plaque evaluation to predict recurrent stroke in symptomatic middle cerebral artery stenosis

Background and purpose We investigated the baseline demographics of patients with severe unilateral atherosclerotic stenosis of the middle cerebral artery(MCA)using multimodal MRI and evaluated the haemodynamic impairments and plaque characteristics of patients who had a recurrent stroke.Materials and methods We retrospectively recruited consecutive patients with severe unilateral atherosclerotic MCA stenosis who underwent arterial spin labelling(ASL)with postlabelling delay(PLD)of 1.5 and 2.5 s,and vessel wall MRI.For each PLD,cerebral blood flow(CBF)maps were generated.Hypoperfusion volume ratio(HVR)from 2 PLD CBF was calculated.An HVR value≥50%was considered as severe HVR.Plaque areas,plaque burden,plaque length and remodelling index were measured.Plaque enhancement at maximal lumen narrowing site were graded.Baseline clinical and imaging characteristics were compared between patients with(event+)and without(event?)1 year ischaemic events.Results Forty-three patients(47.23±12.15 years;28 men)were enrolled in this study.Seven patients had an HVR≥50%.During the 1-year follow-up,7 patients had experienced a recurrent stroke.HVR were significantly higher in the event+than event?(53.17%±29.82%vs 16.9%±15.57%,p=0.0002),whereas no significant difference was detected in plaque areas,plaque burden,remodelling index,plaque length and plaque enhancement grade.The multivariable analysis revealed that a severe HVR was significantly associated with a recurrent stroke(Odds ratio=12.93,95%confidence interval 1.57 to 106.24,p=0.017)after adjusted by hypertension and smoking.Conclusion HVR obtained from two PLD ASL may be a useful imaging predictor of recurrent stroke.

Endovascular therapy for Acute ischemic Stroke Trial (EAST): study protocol for a prospective, multicentre control trial in China

Background and purpose:5 recent trials have shown the benefit of endovascular treatment for acute ischaemic stroke(AIS)due to large vessel occlusion of the anterior circulation.This study aims to evaluate the safety and efficacy of Solitaire thrombectomy in patients with moderate-to-severe stroke in the Chinese population,which has a high prevalence of intracranial atherosclerosis.Methods and analysis:This multicentre prospective control study will involve 17 stroke centres in China,and plans to recruit 150 patients in the intervention group,and 150 patients in the medical group,in which patients meet enrolment criteria but refuse intervention.Patients with AIS due to large vessel occlusion indicated for treatment with Solitaire stent retriever within 12 hours of symptom onset,and who meet the inclusion and exclusion criteria,will be enrolled in this study.The primary efficacy endpoint is functional independence as defined by a modified Rankin Scale(mRS)score≤2 at 90 days or by functional improvement as defined by mRS,using shift analysis.The procedural efficacy endpoint is arterial recanalisation of the occluded target vessel measured by a modified Thrombolysis in Cerebral Infarction(mTICI)score equal or superior to 2b right following the use of the study device.The primary safety endpoint is symptomatic intracranial haemorrhage(sICH)within 24±3 hours postprocedure.Ethics and dissemination:The protocol was approved by the Ethics Committee at the coordinating centre and by the local Institutional Review Board of each participating centre.Trial registration number:NCT02350283.