Lipocalin-2 aggravates blood-brain barrier dysfunction after intravenous thrombolysis by promoting endothelial cell ferroptosis via regulating the HMGB1/Nrf2/HO-1 pathway.

BACKGROUND: Disruption of the blood-brain barrier (BBB) is a major contributor to hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS) following intravenous thrombolysis (IVT). However, the clinical therapies aimed at BBB protection after IVT remain limited. METHODS: One hundred patients with AIS who underwent IVT were enrolled (42 with HT and 58 without HT 24 h after IVT). Based on the cytokine chip, the serum levels of several AIS-related proteins, including LCN2, ferritin, matrix metalloproteinase-3, vascular endothelial-derived growth factor, and X-linked inhibitor of apoptosis, were detected upon admission, and their associations with HT were analyzed. After finding that LCN2 was related to HT in patients with IVT, we clarified whether the modulation of LCN2 influenced BBB dysfunction and HT after thrombolysis and investigated the potential mechanism. RESULTS: In patients with AIS following IVT, logistic regression analysis showed that baseline serum LCN2 (p = 0.023) and ferritin (p = 0.046) levels were independently associated with HT. A positive correlation between serum LCN2 and ferritin levels was identified in patients with HT. In experimental studies, recombinant LCN2 (rLCN2) significantly aggravated BBB dysfunction and HT in the thromboembolic stroke rats after thrombolysis, whereas LCN2 inhibition by ZINC006440089 exerted opposite effects. Further mechanistic studies showed that, LCN2 promoted endothelial cell ferroptosis, accompanied by the induction of high mobility group box 1 (HMGB1) and the inhibition of nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins. Ferroptosis inhibitor ferrostatin-1 (fer-1) significantly restricted the LCN2-mediated BBB disruption. Transfection of LCN2 and HMGB1 siRNA inhibited the endothelial cell ferroptosis, and this effects was reversed by Nrf2 siRNA. CONCLUSION: LCN2 aggravated BBB disruption after thrombolysis by promoting endothelial cell ferroptosis via regulating the HMGB1/Nrf2/HO-1 pathway, this may provide a promising therapeutic target for the prevention of HT after IVT.

Emerging strategies for nerve repair and regeneration in ischemic stroke: neural stem cell therapy.

Ischemic stroke is a major cause of mortality and disability worldwide, with limited treatment options available in clinical practice. The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function. Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect. Neural stem cells regulate multiple physiological responses, including nerve repair, endogenous regeneration, immune function, and blood-brain barrier permeability, through the secretion of bioactive substances, including extracellular vesicles/exosomes. However, due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation, limitations in the treatment effect remain unresolved. In this paper, we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke, review current neural stem cell therapeutic strategies and clinical trial results, and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells. We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.

Dynamic Cerebral Autoregulation After Carotid Endarterectomy.

OBJECTIVE: Studies have shown that dynamic cerebral autoregulation (dCA) is impaired in patients with severe internal carotid artery (ICA) stenosis and that carotid endarterectomy (CEA) may improve dCA in these patients. However, the time course of dCA changes in patients after CEA remains unclear. Therefore, this study aimed to investigate the effects of CEA on the dCA in patients with carotid artery stenosis at different time points. METHODS: This prospective study enrolled 44 patients (19 symptomatic stenosis patients and 25 asymptomatic stenosis patients) who underwent CEA and 44 age- and sex-matched controls. In the CEA group, the patients underwent dCA measurements at baseline, within 3 days, and 1 month after CEA. Transfer function parameters, phase difference (PD), and gain were used to quantify dCA. Changes in dCA before and after CEA were analyzed in detail. RESULTS: The bilateral PD of the patients before CEA was significantly lower than that of the control group. This damage did not improve within 3 days after surgery. One month after surgery, the PD on the affected side of the patients significantly improved compared with before surgery and reached the level of the control group. The PD of affected side across time points in symptomatic and asymptomatic stenosis patients is consistent with that in all patients. CONCLUSIONS: The dCA level did not improve immediately after CEA but significantly improved 1 month after surgery. This suggests that the occurrence of stroke should be considered in the acute period after CEA surgery, and its preventive effect on stroke may be effective after 1 month. CLINICAL IMPACT: We found the dCA level did not improve immediately after CEA but significantly improved 1 month after surgury. This suggests that the occuttencce of stroke and surgical complications (such as cerebral hyperperfusion syndrome) associated with impaired dCA in the acute phase after CEA surgery should be of particular concern.

Characteristics of Epicoccum latusicollum as revealed by genomic and metabolic phenomic analysis, the causal agent of tobacco Epicoccus leaf spot.

Epicoccum latusicollum is a fungus that causes a severe foliar disease on flue-cured tobacco in southwest China, resulting in significant losses in tobacco yield and quality. To better understand the organism, researchers investigated its optimal growth conditions and metabolic versatility using a combination of traditional methods and the Biolog Phenotype MicroArray technique. The study found that E. latusicollum exhibited impressive metabolic versatility, being able to metabolize a majority of carbon, nitrogen, sulfur, and phosphorus sources tested, as well as adapt to different environmental conditions, including broad pH ranges and various osmolytes. The optimal medium for mycelial growth was alkyl ester agar medium, while oatmeal agar medium was optimal for sporulation, and the optimum temperature for mycelial growth was 25°C. The lethal temperature was 40°C. The study also identified arbutin and amygdalin as optimal carbon sources and Ala-Asp and Ala-Glu as optimal nitrogen sources for E. latusicollum. Furthermore, the genome of E. latusicollum strain T41 was sequenced using Illumina HiSeq and Pacific Biosciences technologies, with 10,821 genes predicted using Nonredundant, Gene Ontology, Clusters of Orthologous Groups, Kyoto Encyclopedia of Genes and Genomes, and SWISS-PROT databases. Analysis of the metabolic functions of phyllosphere microorganisms on diseased tobacco leaves affected by E. latusicollum using the Biolog Eco microplate revealed an inability to efficiently metabolize a total of 29 carbon sources, with only tween 40 showing some metabolizing ability. The study provides new insights into the structure and function of phyllosphere microbiota and highlights important challenges for future research, as well as a theoretical basis for the integrated control and breeding for disease resistance of tobacco Epicoccus leaf spot. This information can be useful in developing new strategies for disease control and management, as well as enhancing crop productivity and quality.

Role of lipocalin 2 in stroke.

Stroke is the second leading cause of death worldwide; however, the treatment choices available to neurologists are limited in clinical practice. Lipocalin 2 (LCN2) is a secreted protein, belonging to the lipocalin superfamily, with multiple biological functions in mediating innate immune response, inflammatory response, iron-homeostasis, cell migration and differentiation, energy metabolism, and other processes in the body. LCN2 is expressed at low levels in the brain under normal physiological conditions, but its expression is significantly up-regulated in multiple acute stimulations and chronic pathologies. An up-regulation of LCN2 has been found in the blood/cerebrospinal fluid of patients with ischemic/hemorrhagic stroke, and could serve as a potential biomarker for the prediction of the severity of acute stroke. LCN2 activates reactive astrocytes and microglia, promotes neutrophil infiltration, amplifies post-stroke inflammation, promotes blood-brain barrier disruption, white matter injury, and neuronal death. Moreover, LCN2 is involved in brain injury induced by thrombin and erythrocyte lysates, as well as microvascular thrombosis after hemorrhage. In this paper, we review the role of LCN2 in the pathological processes of ischemic stroke; intracerebral hemorrhage; subarachnoid hemorrhage; and stroke-related brain diseases, such as vascular dementia and post-stroke depression, and their underlying mechanisms. We hope that this review will help elucidate the value of LCN2 as a therapeutic target in stroke.

Role of pontine sub-laterodorsal tegmental nucleus (SLD) in rapid eye movement (REM) sleep, cataplexy, and emotion.

Pontine sub-laterodorsal tegmental nucleus (SLD) is crucial for REM sleep. However, the necessary role of SLD for REM sleep, cataplexy that resembles REM sleep, and emotion memory by REM sleep has remained unclear. To address these questions, we focally ablated SLD neurons using adenoviral diphtheria-toxin (DTA) approach and found that SLD lesions completely eliminated REM sleep accompanied by wake increase, significantly reduced baseline cataplexy amounts by 40% and reward (sucrose) induced cataplexy amounts by 70% and altered cataplexy EEG Fast Fourier Transform (FFT) from REM sleep-like to wake-like in orexin null (OXKO) mice. We then used OXKO animals with absence of REM sleep and OXKO controls and examined elimination of REM sleep in anxiety and fear extinction. Our resulted showed that REM sleep elimination significantly increased anxiety-like behaviors in open field test (OFT), elevated plus maze test (EPM) and defensive aggression and impaired fear extinction. The data indicate that in OXKO mice the SLD is the sole generator for REM sleep; (2) the SLD selectively mediates REM sleep cataplexy (R-cataplexy) that merges with wake cataplexy (W-cataplexy); (3) REM sleep enhances positive emotion (sucrose induced cataplexy) response, reduces negative emotion state (anxiety), and promotes fear extinction.

Impact of Stroke Severity on the Smoking Paradox in Patients Treated with Intravenous Thrombolysis.

OBJECTIVE: To our knowledge, no previous studies have investigated the impact of stroke severity on the smoking paradox after intravenous thrombolysis (IVT). We aimed to explore the contribution of stroke severity to the association between smoking and stroke prognosis after IVT. METHODS: We enrolled consecutive patients who received IVT within 4.5 hours from stroke onset. A logistic regression model was used to estimate the unadjusted and adjusted odds ratios (ORs) with their 95% confidence intervals (CIs) for poor functional outcome and mortality at 3 months. RESULTS: Among patients with moderate stroke, smokers experienced a lower risk of 3-month poor outcomes than non-smokers (33.0% vs. 44.4%, unadjusted OR: 0.616; 95% CI: 0.402-0.945). However, among those with severe stroke, smokers had a higher risk of 3-month poor outcomes than non-smokers (81.6% vs. 55.9%, unadjusted OR: 3.496; 95% CI: 1.207-10.127). After adjustment, the negative correlation between smoking and 3-month poor outcome following IVT lost statistical significance in patients with moderate stroke (OR: 0.677 [95% CI: 0.418-1.097]). However, smoking remained a risk factor for 3-month poor outcomes in patients with severe stroke (OR: 4.216 [95% CI: 1.236-14.385]). We also observed a significant interaction between smoking and stroke severity with regard to the risk of poor functional outcomes (p=0.023). However, no such interaction influenced mortality (p=0.901). CONCLUSION: Stroke severity affects the association between smoking and 3-month clinical functional outcomes following IVT.

Validity of high resolution magnetic resonance imaging in detecting giant cell arteritis: a meta-analysis.

OBJECTIVES: This study was designed to evaluate the performance of high-resolution magnetic resonance imaging (HR-MRI) in detecting giant cell arteritis (GCA), evaluate superficial extracranial artery and other MRI abnormalities, and compare three-dimensional (3D) and two-dimensional (2D) techniques. METHODS: PubMed, Web of Science, and Cochrane Library were screened up to March 7, 2021, and further selection was performed according to the eligibility criteria. Quality Assessment of Diagnostic Accuracy Studies-2 was used for quality assessment, and heterogeneity assessment and statistical calculations were also performed. RESULTS: In total, 1851 records were retrieved from online databases, and 15 studies were finally included. Regarding the performance of HR-MRI, the superficial extracranial artery had 75% sensitivity and 89% specificity, respectively, with an area under the receiver operating characteristic curve (AUC) of 0.91. Positive and negative post-test possibilities were 86% and 20%, respectively, with clinical diagnosis as reference. When referenced with temporal artery biopsy, the sensitivity was 91%, specificity was 78%, AUC was 0.92, and positive and negative post-test possibilities were 78% and 10%, respectively. 3D HR-MRI and 2D HR-MRI had 70% and 72% sensitivity, respectively, and 91% and 84% specificity, respectively. CONCLUSIONS: HR-MRI is a valuable imaging modality for GCA diagnosis. It provided high accuracy in the diagnosis of GCA and played a potential role in identifying GCA-related ischemic optic neuropathy. 3D HR-MRI had better specificity than 2D HR-MRI. KEY POINTS: HR-MRI helps clinicians to diagnose GCA. Superficial extracranial arteries and other MRI abnormalities can be assessed with HR-MRI. HR-MRI can help in assessing GCA-related optic neuropathy.

Biological Functions and Regulatory Mechanisms of Hypoxia-Inducible Factor-1α in Ischemic Stroke.

Ischemic stroke is caused by insufficient cerebrovascular blood and oxygen supply. It is a major contributor to death or disability worldwide and has become a heavy societal and clinical burden. To date, effective treatments for ischemic stroke are limited, and innovative therapeutic methods are urgently needed. Hypoxia inducible factor-1α (HIF-1α) is a sensitive regulator of oxygen homeostasis, and its expression is rapidly induced after hypoxia/ischemia. It plays an extensive role in the pathophysiology of stroke, including neuronal survival, neuroinflammation, angiogenesis, glucose metabolism, and blood brain barrier regulation. In addition, the spatiotemporal expression profile of HIF-1α in the brain shifts with the progression of ischemic stroke; this has led to contradictory findings regarding its function in previous studies. Therefore, unveiling the Janus face of HIF-1α and its target genes in different type of cells and exploring the role of HIF-1α in inflammatory responses after ischemia is of great importance for revealing the pathogenesis and identifying new therapeutic targets for ischemic stroke. Herein, we provide a succinct overview of the current approaches targeting HIF-1α and summarize novel findings concerning HIF-1α regulation in different types of cells within neurovascular units, including neurons, endothelial cells, astrocytes, and microglia, during the different stages of ischemic stroke. The current representative translational approaches focused on neuroprotection by targeting HIF-1α are also discussed.

GAS6/Axl Signaling Modulates Blood-Brain Barrier Function Following Intravenous Thrombolysis in Acute Ischemic Stroke.

Background and Purpose: Recent studies have shown that several proteins, including Axl, are related to hemorrhagic transformation (HT) following intravenous thrombolysis by affecting blood-brain barrier (BBB) function. However, the effects of these proteins on BBB function have been studied primarily in animal models. In this study, we aimed to identify serum protein markers that predict HT following intravenous thrombolysis in patients with acute ischemic stroke (AIS) and verify whether these serum proteins regulate BBB function and HT in animal stroke models. Methods: First, 118 AIS patients were enrolled in this study, including 52 HT patients and 66 non-HT patients. In Step 1, baseline serum levels of Axl, angiopoietin-like 4, C-reactive protein, ferritin, hypoxia-inducible factor-1 alpha, HTRA2, Lipocalin2, matrix metallopeptidase 9, platelet-derived growth factor-BB, and tumor necrosis factor alpha were measured using a quantitative cytokine chip. Next, sequence mutations and variations in genes encoding the differentially expressed proteins identified in Step 1 and subsequent function-related proteins were detected. Finally, we verified whether manipulation of differentially expressed proteins affected BBB function and HT in a hyperglycemia-induced rat stroke model. Results: Serum Axl levels were significantly lower in the HT group than in the non-HT group; none of the other protein markers differed significantly between the two groups. Genetic testing revealed that sequence variations of GAS6 (the gene encoding the Axl ligand)-derived long non-coding RNA, GAS6-AS1, were significantly correlated with an increased risk of HT after intravenous thrombolysis. In animal studies, administration of recombinant GAS6 significantly reduced brain infarction and neurological deficits and attenuated BBB disruption and HT. Conclusions: Lower serum Axl levels, which may result from sequence variations in GAS6-AS1, are correlated with an increased risk of HT after intravenous thrombolysis in stroke patients. Activation of the Axl signaling pathway by the GAS6 protein may serve as a therapeutic strategy to reduce HT in AIS patients.

Association of Admission Leukocyte Count with Clinical Outcomes in Acute Ischemic Stroke Patients Undergoing Intravenous Thrombolysis with Recombinant Tissue Plasminogen Activator.

OBJECTIVE: An increased leukocyte count is positively associated with poor outcomes and all-cause mortality in coronary heart disease, cancer, and ischemic stroke. The role of leukocyte count in acute ischemic stroke (AIS) remains important. We aimed to investigate the association between admission leukocyte count before thrombolysis with recombinant tissue plasminogen activator (rt-PA) and 3-month outcomes in AIS patients. METHODS: This retrospective study included consecutive AIS patients who received intravenous (IV) rt-PA within 4.5 h of symptom onset between January 2016 to December 2018. We assessed outcomes, including short-term hemorrhagic transformation (HT), 3-month mortality, and functional independence (modified Rankin Scale [mRS] score of 0-2 or 0-1). RESULTS: Among 579 patients who received IV rt-PA, 77 (13.3%) exhibited HT at 24 h, 43 (7.4%) died within 3 months, and 211 (36.4%) exhibited functional independence (mRS score: 0-2). Multivariable logistic regression revealed admission leukocyte count as an independent predictor of good and excellent outcomes at 3 months. Each 1-point increase in admission leukocyte count increased the odds of poor outcomes at 3 months by 7.6% (mRS score: 3-6, odds ratio [OR]: 1.076, 95% confidence interval [CI]: 1.003-1.154, p=0.041) and 7.8% (mRS score: 2-6, OR: 1.078, 95% CI: 1.006-1.154, p=0.033). Multivariable regression analysis revealed no association between HT and 3-month mortality. Admission neutrophil and lymphocyte count were not associated with 3-- month functional outcomes or 3-month mortality. CONCLUSION: A lower admission leukocyte count independently predicts good and excellent outcomes at 3 months in AIS patients undergoing rt-PA treatment.

Association between ABCB1 (3435C>T) polymorphism and susceptibility of colorectal cancer: A meta-analysis.

Studies on the relationship between ABCB1 3435C>T polymorphism (rs1045642) and colorectal cancer (CRC)susceptibility have yielded inconclusive results. To clarify this issue, we undertook a meta-analysis to investigate the relationship between rs1045642 and CRC risk.Three electronic scientific publication databases (Cochrane Library, Pubmed, Embase) were screened using specific search terms. Relevant literature was identified using literature traceability methods. Selected publications were evaluated according to the inclusion and exclusion criteria. Effect size information (odds ratio and the corresponding 95% confidence interval [CI]) was obtained following quality assessment and data extraction from the included publications, and a meta-analysis conducted. Statistical analysis was performed with the Stata sofz (Version 13.0) software.Overall, 17 case-control studies involving 7129 CRC patients and 7710 healthy control subjects satisfied the criteria for inclusion in the meta-analysis. There was no significant association between ABCB1 3435C>T polymorphism and CRC risk in any of the genetic models. In the CC versus CT model (I = 20.9%, Pheterogeneity = .276), CC versus CT + TT model (I = 45.6%, Pheterogeneity = .102) and CT versus CC + TT model (I = 17.8%, Pheterogeneity = .298) analyses, between-study heterogeneities were detected as significant in Asian populations. In the CT versus TT model (I = 24%, Pheterogeneity = .254) and CC + CT versus TT model (I = 0, Pheterogeneity = .55), between-study heterogeneities were found to be significant in groups of different populations.The meta-analysis described here suggests that the ABCB1 3435C>T polymorphism is not related to CRC susceptibility.

Primary Angiitis of the Central Nervous System Mimicking Glioblastoma: A Case Report and Literature Review.

Primary angiitis of the central nervous system (PACNS) is a rare disorder resulting in idiopathic inflammation affecting the parenchymal and leptomeningeal vessels confined to the central nervous system (CNS), of which a tumor-like mass lesion is an even rare subtype. We described a case of PACNS initially misdiagnosed as glioblastoma. The patient was a 35 year-old female with right-sided weakness and expressive dysphasia. Brain MRI showed a tumor-like lesion highly suggestive of glioblastoma, therefor surgical removal was done. After a resection and an exhaustive workup, PACNS was ultimately diagnosed. The case illustrates a type of imaging presentation of PACNS that is often misdiagnosed as high-grade glioma. Differentiation between tumor-like PACNS lesions and actual CNS tumors is challenging due to similar MR images. To avoid unnecessary surgical interventions, we summarized previously reported mass-forming PACNS cases in adults from January 1, 2000, to December 31, 2018 and the imaging characteristics of PACNS. Some less commonly used diagnostic methods such as MR spectroscopy may also help clinicians distinguish PACNS from its mimics.

Meta-analysis of the Smoker's Paradox in Acute Ischemic Stroke Patients Receiving Intravenous Thrombolysis or Endovascular Treatment.

INTRODUCTION: The existence of the smoker's paradox is controversial and potential mechanisms have not been explained. We aimed to explore the association between cigarette smoking and functional outcome at 3 months in patients with acute ischemic stroke who were treated with intravenous thrombolysis (IVT) or endovascular treatment (EVT). METHODS: This meta-analysis was conducted in accordance with the PRISMA guidelines. Studies exploring the association between smoking and good functional outcome (modified Rankin Scale score ≤ 2) following IVT or EVT were searched via the databases of PubMed, Embase, and the Cochrane Library from inception to August 8, 2018. Information on the characteristics of included studies was independently extracted by two investigators. Data were pooled using a random-effects or fixed-effects meta-analysis according to the heterogeneity of included studies. RESULTS: Among 20 identified studies, 15 reported functional outcomes following IVT, and five reported functional outcomes following EVT. Unadjusted analyses showed that smoking increased the odds of good functional outcomes with a pooled odds ratio (OR) of 1.48 (95% confidence interval [CI]: 1.36-1.60) after IVT and 2.10 (95% CI: 1.47-3.20) after EVT. Of IVT studies, only eight reported outcomes adjusted for covariates and none of the EVT studies reported adjusted outcomes. After adjustment, the relation between smoking and good functional outcome following IVT lost statistical significance (OR 1.14 [95% CI: 0.81-1.59]). CONCLUSION: Our meta-analysis suggested that smoking was not associated with good functional outcome (mRS ≤ 2) at 3 months in patients with acute ischemic stroke who were treated with intravenous thrombolysis. IMPLICATIONS: The existence of the smoker's paradox is controversial. A previous letter by Plas et al. published in 2013 reported a positive result for the association between smoking and good functional outcome at 3 months in acute ischemic stroke patients who received intravenous thrombolysis (IVT). However, a major limitation of their meta-analysis was that the process of data synthesis was based on unadjusted data. Therefore, we conducted this meta-analysis to investigate the association based on adjusted data and a larger sample size. Our meta-analysis suggested that smoking was not associated with good functional outcome after adjusting for covariates.

Changes in cerebral autoregulation and blood biomarkers after remote ischemic preconditioning.

OBJECTIVE: To determine the effect of remote ischemic preconditioning (RIPC) on dynamic cerebral autoregulation (dCA) and various blood biomarkers in healthy adults. METHODS: A self-controlled interventional study was conducted. Serial measurements of dCA were performed at 7 time points (7, 9, and 11 am; 2, 5, and 8 pm, and 8 am on the next day) without or with RIPC, carried out at 7:20 to 8 am. Venous blood samples were collected at baseline (7 am) and 1 hour after RIPC, and blood biomarkers, including 5 neuroprotective factors and 25 inflammation-related biomarkers, were measured with a quantitative protein chip. RESULTS: Fifty participants were enrolled (age 34.54 ± 12.01 years, 22 men). Compared with the results on the day without RIPC, dCA was significantly increased at 6 hours after RIPC, and the increase was sustained for at least 24 hours. After RIPC, 2 neuroprotective factors (glial cell-derived neurotrophic factor and vascular endothelial growth factor-A) and 4 inflammation-related biomarkers (transforming growth factor-ß1, leukemia inhibitory factor, matrix metallopeptidase-9, and tissue inhibitor of metalloproteinase-1) were significantly elevated compared with their baseline levels. Conversely, monocyte chemoattractant protein-1 was significantly lower compared with its baseline level. CONCLUSIONS: RIPC induces a sustained increase of dCA from 6 to at least 24 hours after treatment in healthy adults. In addition, several neuroprotective and inflammation-related blood biomarkers were differentially regulated shortly after RIPC. The increased dCA and altered blood biomarkers may collectively contribute to the beneficial effects of RIPC on cerebrovascular function. CLINICALTRIALSGOV IDENTIFIER: NCT02965547.

Study on the Clinical, Imaging, and Pathological Characteristics of 18 Cases with Primary Central Nervous System Vasculitis.

BACKGROUND: To summarize the characteristics of primary central nervous system vasculitis from clinical, imaging, and pathological aspects by retrospective study. METHODS: From March 2015 to December 2017, the data of the inpatients of primary central nervous system vasculitis in first Hospital of Jilin University were collected, and their clinical manifestation, imaging, and pathological characteristics were analyzed by using a descriptive method. RESULTS: There were 18 patients, 10 males (55.56%) and 8 females (44.44%) separately. The age ranges from 16 years old to 49 years old, with the median age of 32 years old. There were 8 cases (44.44%) of epileptic seizure, 6 cases (33.33%) of abnormal behavior and cognition, 10 cases (55.56%) with sensorimotor abnormalities, 4 cases (22.22%) with dizziness, 4 cases (22.22%) with headache, 2 cases (11.11%) with facial pain, 2 cases (11.11%) with blurred vision, and 2 cases (11.11%) with unstable walking. Eight patients (44.44%) were identified with cerebral spinal fluid abnormalities. There were 12 cases (66.67%) with bilateral lesions and 6 cases (33.33%) with unilateral lesions, including the frontal lobe (18 cases, 100%), the parietal lobe (10 cases, 55.56%), the temporal and occipital lobe (8 cases, 44.44%). There were 12 cases (66.67%) combined with subcortical white matter involvement, 6 cases (33.33%) combined with meningeal involvement, 2 cases (11.11%) complicated with basal ganglia involvement and 2 cases (11.11%) complicated with spinal cord involvement. Most of the lesions were with unclear border (16 cases, 88.89%), 2 cases (11.11%) were with clear border. Cortical atrophy was identified in 6 cases (33.33%). There were 12 cases (66.67%) with the enhancement of the lesions and meningeal. The 3D Vessel Wall magnetic resonance imaging (VW-MRI) showed uniform thickness in all patients (18/18) with contrast enhancement of the vessel wall of the vasculitis artery. CONCLUSIONS: The clinical manifestation and imaging in primary central nervous system vasculitis are diverse. The 3D VW-MRI could achieve quantification assessment of vasculitis and provide more utility for primary angiitis of the central nervous system.

Anti-inflammation conferred by stimulation of CD200R1 via Dok1 pathway in rat microglia after germinal matrix hemorrhage.

CD200 has been reported to be neuroprotective in neurodegenerative diseases. However, the potential protective effects of CD200 in germinal matrix hemorrhage (GMH) have not been investigated. We examined the anti-inflammatory mechanisms of CD200 after GMH. A total of 167 seven-day-old rat pups were used. The time-dependent effect of GMH on the levels of CD200 and CD200 Receptor 1 (CD200R1) was evaluated by western blot. CD200R1 was localized by immunohistochemistry. The short-term (24 h) and long-term (28 days) outcomes were evaluated after CD200 fusion protein (CD200Fc) treatment by neurobehavioral assessment. CD200 small interfering RNA (siRNA) and downstream of tyrosine kinase 1 (Dok1) siRNA were injected intracerebroventricularly. Western blot was employed to study the mechanisms of CD200 and CD200R1. GMH induced significant developmental delay and caused impairment in both cognitive and motor functions in rat pups. CD200Fc ameliorated GMH-induced damage. CD200Fc increased expression of Dok1 and decreased IL-1beta and TNF-alpha levels. CD200R1 siRNA and Dok1 siRNA abolished the beneficial effects of CD200Fc, as demonstrated by enhanced expression levels of IL-1beta and TNF-alpha. CD200Fc inhibited GMH-induced inflammation and this effect may be mediated by CD200R1/Dok1 pathway. Thus, CD200Fc may serve as a potential treatment to ameliorate brain injury for GMH patients.

Hematoma volume is a predictive factor of disturbed autoregulation after spontaneous intracerebral hemorrhage.

BACKGROUND: Dynamic cerebral autoregulation (dCA) is probably disturbed after spontaneous intracerebral hemorrhage (ICH) and could be an independent predictor of clinical outcome. Clinical determinants of dCA status after ICH need to be further elucidated. METHODS: We finally enrolled 53 patients diagnosed with supratentorial ICH within 6days from onset. DCA was assessed 4-6days after ICH onset by monitoring middle cerebral artery blood flow velocities and simultaneous arterial blood pressure continuously, utilizing transcranial Doppler combined with a servo-controlled finger plethysmograph. Cerebral autoregulation was evaluated by phase difference (PD) in low frequency (0.06-0.12Hz) range derived from transfer function analysis. The previous clinical history was collected including hypertension, diabetes mellitus, prior stroke, smoking, heavy drinking history. Laboratory results during hospitalization were utilized for further risk factors screening, including fasting blood glucose, glycosylated hemoglobin A (1C), total cholesterol, low density lipoprotein cholesterol and homocysteine, etc. Computed tomography scans were performed to collect neuroimaging data, including hematoma location, volume and presence of intraventricular hemorrhage. Univariate and multivariate linear analyses were adopted to explore the relationship between clinical and laboratory variables and bilateral PD respectively. RESULTS: In ICH patients, PD was lower (indicating disturbed autoregulation) both on the ipsilateral (37.53±17.78 degree, P<0.001) and contralateral (34.45±14.92 degree, P<0.001) side of hematoma compared with healthy controls (56.13±16.11 degree). Hematoma volume was independently associated with ipsilateral PD according to multivariate analysis (ß=-0.383, P=0.024) after adjustment for clinical and laboratory factors. CONCLUSIONS: DCA is bilaterally disturbed after supratentorial ICH. Larger hematoma volume is likely to independently predict poorer cerebral autoregulation status ipsilateral to hematoma.

Prevalence of stroke and associated risk factors: a population based cross sectional study from northeast China.

OBJECTIVES: Epidemiological studies aimed at stroke and its risk factors can help identify persons at higher risk and therefore promote stroke prevention strategies. We aimed to explore the current prevalence of stroke and its associated risk factors in northeast China. DESIGN: Population based cross sectional study. SETTING: Data were collected using a structured precoded questionnaire designed by the Stroke Screening and Prevention Programme of the National Health and Family Planning Commission of China, between January and March 2016. PARTICIPANTS: 4100 permanent residents, aged 40 years or older, who had lived in Dehui City of Jilin Province for more than 6 months volunteered to participate in the survey, with a response rate of 92.2%. For the purpose of the present analysis, 48 subjects were excluded due to missing values, giving a total of 4052 people included in this analysis. MAIN OUTCOME MEASURE: The questionnaire included demographic characteristics, stroke related behavioural factors, personal and family medical history of stroke, physical examination and laboratory testing. RESULTS: The overall prevalence of stroke in Jilin Province was 7.2% (95% CI 6.3% to 8.2%). Of all stroke cases, 91.7% (95% CI 87.4% to 94.6%) were ischaemic stroke and 8.3% (95% CI 5.4% to 12.6%) were haemorrhagic stroke. The prevalence rates of dyslipidaemia, smoking and hypertension were ranked as the top three cerebrovascular risk factors and were 62.1%, 61.8% and 57.3%, respectively. We found that hypertension, dyslipidaemia and lack of exercise were associated with ischaemic stroke. However, only hypertension (OR=4.064, 95% CI 1.358 to 12.160) was significantly associated with haemorrhagic stroke. CONCLUSIONS: The prevalence of stroke, especially ischaemic stroke, and associated cerebrovascular risk factors among adults aged 40 years or older in northeast China were high. A higher regional prevalence of hypertension, dyslipidaemia and lack of exercise may be responsible.