A more consistent intraluminal rhesus monkey model of ischemic stroke

Endovascular surgery is advantageous in experimentally induced ischemic stroke because it causes fewer cranial traumatic lesions than invasive surgery and can closely mimic the pathophysiology in stroke patients. However, the outcomes are highly variable, which limits the accuracy of evaluations of ischemic stroke studies. In this study, eight healthy adult rhesus monkeys were randomized into two groups with four monkeys in each group: middle cerebral artery occlusion at origin segment(M1) and middle cerebral artery occlusion at M2 segment. The blood flow in the middle cerebral artery was blocked completely for 2 hours using the endovascular microcoil placement technique(1 mm × 10 cm)(undetachable), to establish a model of cerebral ischemia. The microcoil was withdrawn and the middle cerebral artery blood flow was restored. A reversible middle cerebral artery occlusion model was identified by hematoxylin-eosin staining, digital subtraction angiography, magnetic resonance angiography, magnetic resonance imaging, and neurological evaluation. The results showed that the middle cerebral artery occlusion model was successfully established in eight adult healthy rhesus monkeys, and ischemic lesions were apparent in the brain tissue of rhesus monkeys at 24 hours after occlusion. The rhesus monkeys had symptoms of neurological deficits. Compared with the M1 occlusion group, the M2 occlusion group had lower infarction volume and higher neurological scores. These experimental findings indicate that reversible middle cerebral artery occlusion can be produced with the endovascular microcoil technique in rhesus monkeys. The M2 occluded model had less infarction and less neurological impairment, which offers the potential for application in the field of brain injury research.

Latest progress in the research of protein kinase C(PKC)isoform-specific signaling and PKC-modulated autophagy in ischemic stroke

Ischemic stroke is a major cause of morbidity and mortality,and currently there is no effective treatment.The family of protein kinase C(PKCs)could phosphorylate serine or threonine residues of its substrate proteins and play a key role in the ischemia/reperfusion injury.Autophagy is essential for maintaining cell homeostasis under physiological condition and acts as a double-edged sword in the process of ischemic neuronal death.In this article,we reviewed the PKCs isoform-specific signaling pathways and PKC-modulated autophagy in ischemic stroke.

Relationship of Post-Stroke Aphasic Types with Sex, Age and Stroke Types

Aim: To explore what is the relationship of the types of post-stroke aphasia with sex, age and stroke types. Methods: Retrospective analysis was administrated on data of 421 patients with acute stroke. Western battery aphasia was used to measure aphasiac type and aphasia quotient (AQ) score. The patients were divided into three age groups: young, middle-aged and elderly. The stroke types were classified into cerebral infraction (CI) and intracerebral hemorrhage (ICH). Results: All subjects were right-handed, which males and females accounted for 69.60% and 30.40%, respectively. There were 116 cases of Broca’s aphasia (85 males), 35 cases of Wernicke’s aphasia (20 males), 15 cases of conductive aphasia (10 males), 63 cases of transcortical motor aphasia (50 males), 11 cases of transcortical sensory aphasia (8 males), 27 cases of transcortical combined aphasia (13 males), 73 cases of anomic aphasia (47 males) and 81 cases of global aphasia (60 males). Male patients (69.60%) have a significantly higher morbidity of aphasia than that of females (30.40%) after stroke (χ2 = 11.57, P = 0.003), especially those under 65 years old (73.38%). For people 65 years and older, the morbidity of female (42.97%) tends to increase with age. Sex has no significant influence on the types of aphasia (χ2 = 13.84, P = 0.054). Broca’s aphasia is the most common type inboth male and female (29.01%, 24.22%, respectively). The distribution of aphasic types has no obvious difference among three age groups (χ2 = 14.94, P= 0.382). Aphasia induced by CI (306 cases) is more common than that by ICH (115 cases), but there was no difference in distribution of types of aphasia (χ2 = 13.23, P = 0.067). Conclusions: Male patients have a significantly higher level of morbidity of aphasia than females after stroke and a lower average age of onset than females. Broca’s aphasia is the most common one in both male and female. Broca’s aphasia, global and anomic aphasia are the most common aphasic types in both CI and ICH patients, except the female with ICH.

An Integrated Analysis of Risk Factors of Cognitive Impairment in Patients with Severe Carotid Artery Stenosis

Objective To investigate cognitive dysfunction in patients with carotid artery stenosis(CAS) and potential risk factors related to cognitive-especially memory-dysfunction. Methods Forty-seven patients with carotid artery stenosis were recruited into our study cohort. The Mini-Mental State Examination(MMSE) and the Montreal Cognitive Assessment(MoCA) were adopted to assess cognitive function, the Wechsler Memory Scale(WMS) to assess memory function, high-resolution MRI and enhanced ultrasound to evaluate carotid plaques, and computed tomography perfusion(CTP) imaging to evaluate intracranial blood perfusion. Single-factor analysis and multiple-factor regression analysis were used to analyze potential risk factors of cognitive impairment. Results Mini-Mental State Examination test results showed that 22 patients had cognitive impairment, and MoCA test results showed that 10 patients had cognitive impairment. Analysis of various risk factors indicated that the average memory quotient of female patients was higher than that of males(P = 0.024). The cognitive and memory performance of those with an educational background above high school were significantly better than those of participants with high school or lower(P = 0.045). Patients with abnormal intracranial perfusion performed worse on the MMSE test(P = 0.024), and their WMS scores were significantly lower(P = 0.007). The MMSE scores and the memory quotients were significantly lower in patients with a history of cerebral infarction(MMSE, P = 0.047, memory quotient score, P = 0.018). Conclusion A history of cerebral infarction and abnormal cerebral perfusion are associated with decline in overall cognitive function and memory in patients with carotid stenosis. Being female and having an educational background above high school may be protective factors in the development of cognitive dysfunction.

Animal models and molecular mechanism of major depressive disorder

Major depressive disorder(MDD)has been a devastating neurological problem in modern history.However,therapeutic strategies to relief the disease are inadequate.The limit in understanding of the molecular mechanism of MDD has been holding back discovery of new therapies.Behind this problem is the establishment of animal models to truly reflect human MDD pathology.In this review,we discuss our current understanding of the molecular mechanism of MDD and the strength and weakness of rodent models of depression.Developing new models of MDD and finding new drugable targets are still important steps to discover new therapies against MDD.

The biogenesis and biological roles of tRNA-derived short RNAs

In recent years, next-generation sequencing (NGS) technologies targeting the microRNA (miRNA)transcriptome revealed the existence of tRNA-derived short RNAs: tRNA halves (tiRNAs) and tRNA-derived fragments (tRFs). These small RNAs represent a novel type of small non-coding RNAs (sncRNAs), which are heterogeneous in size, nucleotide composition and biogenesis, and have been suggested to be involved in translation, cell proliferation, priming of viral reverse transcriptases, regulation of gene expression, modulation of the DNA damage response, tumor suppression and neurological disorders. Herein, we review the mechanism of their biogenesis and discuss in detail the regulatory roles they play in cell physiology. We also point out that the biological function of tRNA-derived short RNAs will be understood better as research moves forward, and that this knowledge will find its way into clinical application in the near future.

Rationale and design of Patient-centered Retrospective Observation of Guideline-Recommended Execution for Stroke Sufferers in China: China PROGRESS

Background In 2009,China launched ambitious healthcare reform plans to provide affordable and equitable basic healthcare for all patients,including the substantial number of patients who had a stroke.However,little is known about the pattern of evidence-based stroke care and outcomes across hospitals,regions and time during the last decade.Aims The Patient-centered Retrospective Observation of Guideline-Recommended Execution for Stroke Sufferers in China(China PROGRESS)Study aims to use findings from a representative sample of Chinese hospitals over the last decade to improve future stroke care for patients hospitalised with ischaemic stroke(IS)or transient ischaemic attack(TIA).Design The China PROGRESS Study will use a two-stage cluster sampling method to identify over 32000 patient records from 208 hospitals across the Eastern,Central and Western geographical regions in China.To assess the temporal trends in patient characteristics,treatment and outcomes,study investigators will select records from 2005,2010 and 2015.A double data reading/entry system will be developed to conduct this assessment.A central coordinating centre will monitor case ascertainment,data abstraction and data management.Analyses will examine patient characteristics,testing patterns,in-hospital treatment and outcomes,and variations across regions and across time.Conclusions The China PROGRESS Study is the first nationally representative study that aims to better understand care quality and outcomes for patients with IS or TIA before and after the national healthcare reform in China.This initiative will translate findings into clinical practices that improve care quality for patients who had a stroke and policy recommendations that allow these changes to be implemented widely.Ethics approval This study has also been approved by the central institutional review board(IRB)at Beijing Tiantan Hospital.

Persistent depression is a predictor of quality of life in stroke survivors: results from a 5-year follow-up study of a Chinese cohort

Background:Whether the time course of post-stroke depression (PSD) can be used to predict the quality of life (QoL) of patients with late-stage stroke remains unclear,this study investigated whether persistent depression at 1 year after stroke predicts QoL at 5 years following stroke.Methods:We analyzed the demographic and clinical data of patients with stroke in 56 hospitals across China that participated in the Prospective Cohort Study on the Incidence and Outcome of Patients with PSD in China Study.Follow-up assessments were performed at the following time points after stroke:in person,2 weeks,3 months,6 months,and 1 year;by telephone,5 years.National Institutes of Health Stroke Scale (NIHSS) score on admission,recurrence,disability,depression,QoL,and chronic complications were recorded.Depression was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders.QoL was measured using short form-12 (SF-12).Multivariable ordinal logistic regression analysis was used to identify factors that independently affected the physical component summary (PCS) and mental component summary (MCS) scores of the SF-12.Results:Of the 801 patients evaluated in this study,80 had persistent depression.The multivariable regression analysis of data obtained at 5 years showed that persistent depression at 1 year (odds ratio [OR]:0.48;95% confidence interval [CI]:0.29-0.81) and disability at 5 years (OR:0.34;95% CI:0.23-0.49) were associated with poor MCS scores at 5 years.Old age,a high NIHSS score on admission,disability at 5 years,and stroke recurrence within 5 years were associated with poor PCS scores at the 5-year follow-up.Conclusions:Persistent depression at the 1-year follow-up could predict poor MCS scores at the 5-year follow-up.The development of interventional strategies targeting post-stroke patients with persistent depression is warranted.

White matter connection's damage,not cortical activation, leading to language dysfunction of mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes

Mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes (MELAS) is a metabolic disorder characterized by hyperlactic acidemia and stroke-like symptoms.

Gastrointestinal bleeding during acute ischaemic stroke hospitalisation increases the risk of stroke recurrence

Objective Gastrointestinal(GI)bleeding in patients who had a stroke is strongly associated with a higher risk of death and loss of independence.However,it is unknown whether GI bleeding increases risk for recurrence of stroke.In this study,we assess the potential relationship between GI bleeding and stroke recurrence in patients within 12 months of an acute ischaemic stroke(AIS),using the China National Stroke Registry(CNSR).Methods This study included 22216 patients who had an ischaemic stroke included in the CNSR from 2007 to 2008.We analysed baseline patient characteristics,GI bleeding and outcomes of patients who had an AIS,specifically stroke recurrence at 3,6 and 12 months.We used multivariable logistic regression to evaluate a possible association between GI bleeding and stroke recurrence.results Of the 12415 patients included in our study,12.3%,15.5%and 17.7%had a stroke recurrence at 3,6 and 12 months,respectively.GI bleeding was an independent stroke recurrence risk factor in patients after ischaemic stroke at 3 months(adjusted OR 1.481,95%CI 1.118 to 1.962),6 months(adjusted OR 1.448,95%CI 1.106 to 1.896)and 12 months(adjusted OR 1.350;95%CI 1.034 to 1.763).Conclusion GI bleeding was associated with the increased risk of stroke recurrence after an AIS.

Quality improvement of nursing on patients with complex cerebral arteriovenous malformation undergoing hybrid surgery:a prospective single-center study

Background:We sought to explore an optimal clinical nursing mode following a hybrid surgery for cerebral arteriovenous malformation.Methods:Patients with complex cerebral arteriovenous malformations seen in our neurosurgery department from January 2016 to December 2017 were prospectively enrolled.The hybrid surgery protocol included“angiographic diagnosis,surgical resection,and intraoperative angiographic evaluation”and“angiographic diagnosis and embolization,surgical resection,and intraoperative angiographic evaluation”.The patients were randomly stratified into intensive care group and routine care group.After surgery,intensive or routine care was provided,and the prognosis of patients was evaluated,with a subsequent comparative analysis.Results:A total of 109 cases were divided into the routine nursing group(n=54 cases)and intensive nursing group(n=55 cases).There were no significant differences between the two groups in baseline data before surgery.Postoperative lung infection in the intensive nursing group was significantly less frequent than those in the routine nursing group(5.5%vs.18.5%,P=0.039)with pulmonary infection and lower extremity venous thrombosis(5.5%vs.24.1%,P=0.006).The average hospital stay in the intensive nursing group was 14.4±5.78 days,which was significantly lower than that in the routine nursing group(19.3±6.38 days,P=0.013).At 3 months’follow-up after surgery,the Generic Quality of Life Inventory-74(GQOLI-74)dimension score and GQOLI-74 total score in the enhanced group were significantly better than those in the routine nursing group(P=0.017 and 0.023,respectively).Conclusions:Intensive postoperative nursing can improve the safety of patients after hybrid surgery,reduce the postoperative complications and the average length of hospital stay,and improve the quality of life of patients.

Prognostic value of admission hyperglycemia on outcomes of thrombolysis in ischemic stroke patients with or without diabetes

Thrombolytic therapy within 4.5 h from symptom onset is a recognized effective and standard therapy for acute ischemic stroke(AIS),but some patients still have a poor clinical outcome.The evaluation and control of predictors for AIS poor clinical outcomes is integral to achieving optimal treatments,but the prognostic value of admission blood glucose(ABG)for this purpose is unclear and still under debate.ABG evaluated in patients without diabetes mellitus(DM)often suggests acute stress hyperglycemia,while ABG may have a close relationship with long-term blood glucose control in patients with DM.However,in most studies about the influence of ABG on the prognosis of recombinant tissue-type plasminogen activator(rtPA)therapy after AIS,patients were not classified into those with and without DM.The present study was designed to investigate the prognostic value of ABG for clinical outcomes of AIS after thrombolysis according to DM status in a Chinese population.

Safety and efficacy of oral antiplatelet for patients who had acute ischaemic stroke undergoing endovascular therapy

Background and purpose To investigate the safety and efficacy of oral antiplatelet therapy(APT)for patients who had acute ischaemic stroke(AIS),receiving endovascular therapy(EVT).Methods Patients were divided into non-APT group and APT(single APT or dual APT(DAPT)group.The safety and efficacy endpoints at 3-month follow-up were symptomatic intracranial haemorrhage(sICH),recanalisation rate,clinical outcome and mortality.Results Among 915 patients who had AIS,those in APT group(n=199)showed shorter puncture-to recanalisation time,lower frequency of intravenous thrombolysis and more use of tirofiban compared with those in non-antiplatelet group(n=716)(p<0.05 for all).Oral APT was found to be associated with superior clinical outcome compared with non-APT(APT(44.2%)versus non-APT(41.1%)),adjusted OR=2.605,95% CI 1.244 to 5.455,p=0.011).DAPT showed superior clinical outcome compared with non-APT(DAPT(56.5%)versus non-APT(41.1%),adjusted OR=5.405,95% CI 1.614 to 18.102,p=0.006)and lower risk of mortality at 3-month follow-up(DAPT(4.8%)versus non-DAPT(17.7%),adjusted OR=0.008,95%CI 0.000 to 0.441,p=0.019).There was no significant difference in sICH between the two groups.Conclusions Oral APT prior to undergoing EVT is safe and may accompany with superior clinical outcomes.DAPT may associate with superior clinical outcomes and lower risk of mortality.

Remote ischemic conditioning-induced hyperacute and acute responses of plasma proteome in healthy young male adults:a quantitative proteomic analysis

Background: Long-term remote ischemic conditioning (RIC) has been proven to be beneficial in multiple diseases, such as cerebral and cardiovascular diseases. However, the hyperacute and acute effects of a single RIC stimulus are still not clear. Quantitative proteomic analyses of plasma proteins following RIC application have been conducted in preclinical and clinical studies but exhibit high heterogeneity in results due to wide variations in experimental setups and sampling procedures. Hence, this study aimed to explore the immediate effects of RIC on plasma proteome in healthy young adults to exclude confounding factors of disease entity, such as medications and gender. Methods: Young healthy male participants were enrolled after a systematic physical examination and 6-month lifestyle observation. Individual RIC sessions included five cycles of alternative ischemia and reperfusion, each lasting for 5 min in bilateral forearms. Blood samples were collected at baseline, 5 min after RIC, and 2 h after RIC, and then samples were processed for proteomic analysis using liquid chromatography-tandem mass spectrometry method. Results: Proteins related to lipid metabolism (e.g., Apolipoprotein F), coagulation factors (hepatocyte growth factor activator preproprotein), members of complement cascades (mannan-binding lectin serine protease 1 isoform 2 precursor), and inflammatory responses (carboxypeptidase N catalytic chain precursor) were differentially altered at their serum levels following the RIC intervention. The most enriched pathways were protein glycosylation and complement/coagulation cascades. Conclusions: One-time RIC stimulus may induce instant cellular responses like anti-inflammation, coagulation, and fibrinolysis balancing, and lipid metabolism regulation which are protective in different perspectives. Protective effects of single RIC in hyperacute and acute phases may be exploited in clinical emergency settings due to apparently beneficial alterations in plasma proteome profile. Furthermore, the beneficial effects of long-term (repeated) RIC interventions in preventing chronic cardiovascular diseases among general populations can also be expected based on our study findings.

Temporal trends and rural-urban disparities in cerebrovascular risk factors,in-hospital management and outcomes in ischaemic strokes in China from 2005 to 2015:a nationwide serial cross-sectional survey

Background Stroke is the leading cause of mortality in China,with limited evidence of in-hospital burden obtained from nationwide surveys.We aimed to monitor and track the temporal trends and rural-urban disparities in cerebrovascular risk factors,management and outcomes from 2005 to 2015.Methods We used a two-stage random sampling survey to create a nationally representative sample of patients admitted for ischaemic stroke in 2005,2010 and 2015.We sampled participating hospitals with an economic-geographical region-stratified random-sampling approach first and then obtained patients with a systematic sampling approach.We weighed our survey data to estimate the national-level results and assess changes from 2005 to 2015.Results We analysed 28277 ischaemic stroke admissions from 189 participating hospitals.From 2005 to 2015,the estimated national hospital admission rate for ischaemic stroke per 100000 people increased(from 75.9 to 402.7,Ptrend<0.001),and the prevalence of risk factors,including hypertension,diabetes,dyslipidaemia and current smoking,increased.The composite score of diagnostic tests for stroke aetiology assessment(from 0.22 to 0.36,Ptrend<0.001)and secondary prevention treatments(from 0.46 to 0.70,Ptrend<0.001)were improved.A temporal decrease was found in discharge against medical advice(DAMA)(from 15.2%(95%CI 13.7%to 16.7%)to 8.6%(8.1%to 9.0%);adjusted Ptrend=0.046),and decreases in in-hospital mortality(0.7%in 2015 vs 1.8%in 2005;adjusted OR(aOR)0.52;95%CI 0.32 to 0.85)and the composite outcome of in-hospital mortality or DAMA(8.4%in 2015 vs 13.9%in 2005;aOR 0.65;95%CI 0.47 to 0.89)were observed.Disparities between rural and urban hospitals narrowed;however,disparities persisted in in-hospital management(brain MRI:rural-urban difference from−14.4%to−11.2%;cerebrovascular assessment:from−20.3%to−16.7%;clopidogrel:from−2.1%to−10.3%;anticoagulant for atrial fibrillation:from−10.9%to−8.2%)and in-hospital outcomes(DAMA:from 2.7%to 5.0%;composite outcome of in-hospital mortality or DAMA:from 2.4%to 4.6%).Conclusions From 2005 to 2015,improvements in hospital admission and in-hospital management for ischaemic stroke in China were found.A temporal improvement in DAMA and improvements in in-hospital mortality and the composite outcome of in-hospital mortality or DAMA were observed.Disparities between rural and urban hospitals generally narrowed but persisted.

Blood Biomarkers in Minor Stroke and Transient Ischemic Attack

Minor stroke and transient ischemic attack(TIA)are common disorders with a high rate of subsequent disabling stroke, so the early recognition and management of minor stroke and TIA is of great importance. At the moment, the diagnosis of these disorders is based on neurologic deficits in a stroke-clinician's examination of the patient, supplemented by the results of acute brain imaging.However, high variability in TIA diagnosis has been reported between physicians, even trained vascular neurologists, and image-based diagnostic confirmation is not always readily available. Some patients still have ischemic events despite sustained standard secondary preventive therapy. Blood biomarkers are promising to aid in the diagnosis, risk stratification, and individual treatment of minor stroke and TIA. Some studies are being conducted in this field. This mini-review aims to highlight potential biomarkers for diagnosis and those helpful in predicting the risk of future stroke and the selection of treatment.

Staged carotid artery angioplasty and stenting for patients with high-grade carotid stenosis with high risk of developing hyperperfusion injury:a retrospective analysis of 44 cases

Background:Hyperperfusion syndrome(HPS)is a rare but potentially a life-threatening complication after carotid artery angioplasty and stenting(CAS).Staged CAS has been an alternative to prevent HPS.Materials and methods:44 of 908 patients with high-grade internal carotid artery stenosis or near occlusion were at risk of HPS because of poor collateral flow and impaired cerebral blood flow(CBF).They were treated with first(stage 1),followed by a full CAS(stage 2)1 month later.Their 30-day outcomes were tabulated and analysed.Results:During follow-up,1 of the 44(2.2%)patients developed HPS immediately,3(7%)had postprocedural HPS(ie,transcranial Doppler(TCD)>120%)without clinical symptoms and 3(7%)required stenting at stage 1 for carotid dissections.After stage 1,there were significant improvement between the preprocedural and postprocedural CBF(0.98±0.06 vs 0.85±0.05,p<0.05),mean transit time(MTT;1.05±0.05 vs 1.15±0.05,p<0.05),time to peak(TTP;1.04±0.06 vs 1.20±0.06,p<0.05)on CT perfusion(CTP),and CBF(66.41±7.41 vs 44.44±6.43,p<0.05)on TCD.After stage 2,improvement was seen in CBF(1.01±0.07 vs 0.98±0.06,p<0.05),MTT(1.01±0.05 vs 1.05±0.05,p<0.05),TTP(0.99±0.06 vs 1.04±0.06,p<0.05)on CTP and CBF(66.41±7.41 vs 93.78±18.81,p<0.05)on TCD.2 had postoperative increase of middle cerebral artery mean flow velocity of 120%after stage 2 without clinical symptoms.Conclusion:Staged carotid artery stenting probably decreased the chance of developing HPS in this group of selected patients.Although requiring a 2-step intervention,staged CAS may be a safe and effective alternative.

Insomnia is associated with increased mortality in patients with first-ever stroke:a 6-year follow-up in a Chinese cohort study

Objective Insomnia is a highly prevalent disorder among patients suffering from stroke.The association between insomnia and stroke mortality is less studied,particularly using the latest diagnostic criteria.The current study examined the relationship between insomnia and mortality among patients with first-evonal hazard models were used to calculate HRs for stroke er stroke in China.Methods Patients with acute cerebrovascular diseases(stroke)were recruited from 56 hospitals in China's Mainland.Insomnia was defined as difficulty falling asleep,or difficulty staying asleep or waking up early,for at least two consecutive visits.Demographic data,medical history and clinical data were collected.Four follow-up visits occurred within the first year after stroke,and the last follow-up call was conducted 6 years later.Cox proportional hazard models were used to calculate HRs for stroke mortality.results Insomnia was reported by 38.4%(489/1273)of patients at baseline.During the 6 years of follow-up,after adjusting for all confounders,insomnia was found to be associated with increased mortality(HR=1.66,95%CI 1.10 to 2.48).Old age(HR=1.08,95%CI 1.06 to 1.10),stroke recurrence in the first year of follow-up(HR=2.53,95%CI 1.48 to 4.31)and stroke survivors with hypertension(HR=1.62,95%CI 1.04 to 2.53)had substantially higher risk of mortality.Conclusions Besides old age,stroke recurrence in the first year of follow-up and hypertension,insomnia is associated with increased risk of mortality in patients with first-ever stroke in China.More studies about prompt and efficient interventions for insomnia are expected in the future.Trial registration number rctn62169508.