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Background and purpose Toll-like receptors (TLRs) are involved in innate immunity and inflammatory responses in various diseases. Our study aimed to investigate the association the levels of soluble TLR4 (sTLR4) and soluble TLR2 (sTLR2) and clinical outcomes following intracerebral hemorrhage (ICH).Methods Patients admitted to department of Neurology with acute ICH were retrospectively included. Plasma levels of sTLR4 and sTLR2 after ICH were measured by enzyme-linked immunosorbent assay. Poor clinical outcome was defined as a modified Rankin score (mRS) of 3–6 at 3-month and 12-month after onset.Results All 207 patients with ICH and 100 non-stroke controls were included in our analysis. The mean sTLR4 level was 4.53 ± 1.51ng/ml and mean sTLR2 level was 3.65 ± 0.72ng/ml. There was a significant trend towards a worse clinical outcomes with increasing sTLR4 and sTLR2 terciles at 3 and 12 months. According to receiver operating curve (ROC), the sTLR4 was reliable predictor for poor clinical outcome at 3 months (ROC = 0.75) and 12 months (ROC = 0.74). The sTLR2 was less reliable predictor for poor clinical outcome at 3 months (ROC = 0.64) and 12 months (ROC = 0.65). The level of sTLR4 was an independent predictor of poor clinical outcome at 12-month (OR 1.24, 95% CI 1.16 to 1.80; P = 0.019).Conclusions The sTLR4 quantification may provide accurate prognostic information after ICH.

Peripheral nerve regeneration and functional recovery remain a major clinical challenge. Nerve guidance conduit (NGC) that can regulate biological behavior of Schwann cells (SCs) and facilitate axonal regeneration through microenvironmental remodeling is beneficial for nerve regeneration and functional recovery. Gastrodin, a main constituent of a Chinese traditional herbal medicine, has been known to display several biological and pharmacological properties, especially antioxidative, anti‐inflammatory and nerve regeneration. Herein, polyurethane (PU) NGCs modified by different weight ratio of Gastrodin (0, 1 and 5 wt%) were designed for sequential and sustainable drug release, that created a favorable microenvironment for nerve regeneration. The scaffold showed suitable pore structure and biocompatibility in vitro, and evidently promoted morphological and functional recovery of regenerated sciatic nerves in vivo. Compared to the PU and 1%Gastrodin/PU scaffolds, the 5%Gastrodin/PU significantly enhanced the proliferation, migration and myelination of SCs and up-regulated expression of neurotrophic factors, as well as induction of the differentiation of PC12 cells. Interestingly, the obvious anti-inflammatory response was observed in 5%Gastrodin/PU by reduced expression of TNF-α and iNOS, which also evidenced by the few fibrous capsule formation in the subcutaneous implantation. Such a construct presented a similarity to autograft in vivo repairing a 10 mm sciatic nerve defects. It was able to not only boost the regenerated area of nerve and microvascular network, but also facilitate functional axons growth and remyelination, leading to highly improved functional restoration. These findings demonstrate that the 5%Gastrodin/PU NGC efficiently promotes nerve regeneration, indicating their potential for use in peripheral nerve regeneration applications., Graphical abstract Image 1, Highlights • NGC with a sustained release of Gastrodin creates a favorable microenvironment. . • Gastrodin/PU has superior anti-inflammatory effects. • SCs-mediated tissue engineering strategies effectively drive myelination. • 5Gastrodin/PU boosts nerve regeneration and functional restoration in vivo.

Background: A valid, reliable, accessible, engaging, and affordable digital cognitive screen instrument for clinical use is in urgent demand. Objective: To assess the clinical utility of the MemTrax memory test for early detection of cognitive impairment in a Chinese cohort. Methods: The 2.5-minute MemTrax and the Montreal Cognitive Assessment (MoCA) were performed by 50 clinically diagnosed cognitively normal (CON), 50 mild cognitive impairment due to AD (MCI-AD), and 50 Alzheimer’s disease (AD) volunteer participants. The percentage of correct responses (MTx-% C), the mean response time (MTx-RT), and the composite scores (MTx-Cp) of MemTrax and the MoCA scores were comparatively analyzed and receiver operating characteristic (ROC) curves generated. Results: Multivariate linear regression analyses indicated MTx-% C, MTx-Cp, and the MoCA score were significantly lower in MCI-AD versus CON and in AD versus MCI-AD groups (all with p≤0.001). For the differentiation of MCI-AD from CON, an optimized MTx-% C cutoff of 81% had 72% sensitivity and 84% specificity with an area under the curve (AUC) of 0.839, whereas the MoCA score of 23 had 54% sensitivity and 86% specificity with an AUC of 0.740. For the differentiation of AD from MCI-AD, MTx-Cp of 43.0 had 70% sensitivity and 82% specificity with an AUC of 0.799, whereas the MoCA score of 20 had 84% sensitivity and 62% specificity with an AUC of 0.767. Conclusion: MemTrax can effectively detect both clinically diagnosed MCI and AD with better accuracy as compared to the MoCA based on AUCs in a Chinese cohort.

Vascular grafts must avoid negative inflammatory responses and thrombogenesis to prohibit fibrotic deposition immediately upon implantation and promote the regeneration of small diameter blood vessels (, Graphical abstract Gastrodin-modified polyurethane exhibited both anti-coagulation and anti-inflammatory properties,further led to angiogenesis, serving as a promising blood-contacting anti-thrombotic material.Image 1, Highlights • Gastrodin-modified PU films had desirable pore structure and mechanical properties. • Gastrodin/PU exhibited better anti-coagulation and anti-inflammatory response. • 2Gastrodin/PU effectively drove adhesion and proliferation of HUVECs in vitro. • 2Gastrodin/PU facilitated neo-vessels formation in vivo subcutaneous implantation. • Gastrodin/PU is a potential candidate blood-contacting anti-thrombotic material.

Background: The widespread incidence and prevalence of Alzheimer’s disease and mild cognitive impairment (MCI) has prompted an urgent call for research to validate early detection cognitive screening and assessment. Objective: Our primary research aim was to determine if selected MemTrax performance metrics and relevant demographics and health profile characteristics can be effectively utilized in predictive models developed with machine learning to classify cognitive health (normal versus MCI), as would be indicated by the Montreal Cognitive Assessment (MoCA). Methods: We conducted a cross-sectional study on 259 neurology, memory clinic, and internal medicine adult patients recruited from two hospitals in China. Each patient was given the Chinese-language MoCA and self-administered the continuous recognition MemTrax online episodic memory test on the same day. Predictive classification models were built using machine learning with 10-fold cross validation, and model performance was measured using Area Under the Receiver Operating Characteristic Curve (AUC). Models were built using two MemTrax performance metrics (percent correct, response time), along with the eight common demographic and personal history features. Results: Comparing the learners across selected combinations of MoCA scores and thresholds, Naïve Bayes was generally the top-performing learner with an overall classification performance of 0.9093. Further, among the top three learners, MemTrax-based classification performance overall was superior using just the top-ranked four features (0.9119) compared to using all 10 common features (0.8999). Conclusion: MemTrax performance can be effectively utilized in a machine learning classification predictive model screening application for detecting early stage cognitive impairment.

The extracellular matrix provides cells with a support structure and an attachment site in actual substrate. Its biochemical and surface properties play an important role in and have significant impact on cell attachment, proliferation, migration, differentiation, and gene expression. Leveraging the hydrophilicity and neuroprotective of gastrodin, a gastrodin/polyurethane (PU) elastomer was developed utilizing in situ polymerization and salt-leaching methods. The results showed that gastrodin/PU film had a good flexibility and supporting strength, as well as hydrophilicity. Thus film possessed highly surface area, interconnected porous structure with a pore size (10~60 μm) for cell attachment, and could provide surface cues to augment neurite extension. For PC12 cells cultured within the films, especially the 5gastrodin/PU group, presented a progressive increase with time, coupled with the upregulation of brain-derived neurotrophic factor and glial cell derived neurotrophic factor expression. This is the first report on the construction of a gastrodin/PU porous film, and the results reveal its promise as a scaffold material for neural tissue engineering.

SLIT and NTRK-like protein-5 (SliTrk5) is one of the six members of SliTrk protein family, which is widely expressed in the central nervous system (CNS), regulating and participating in many essential steps of central nervous system development, including axon and dendritic growth, neuron differentiation, and synaptogenesis. SliTrk5, as a neuron transmembrane protein, contains two important conservative domains consisting of leucine repeats (LRRs) located at the amino terminal in the extracellular region and tyrosine residues (Tyr) located at the carboxyl terminal in the intracellular domains. These special structures make SliTrk5 play an important role in the pathological process of the CNS. A large number of studies have shown that SliTrk5 may be involved in the pathogenesis of CNS diseases, such as obsessive-compulsive-disorder (OCD), attention deficit/hyperactivity disorder (ADHD), glioma, autism spectrum disorders (ASDs), and Parkinson’s disease (PD). Targeting SliTrk5 is expected to become a new target for the treatment of CNS diseases, promoting the functional recovery of CNS. The purpose of this article is to review the current research progression of the role of SliTrk5 in CNS and its potential mechanisms in CNS diseases.

BackgroundThe dementia and affective disorders are common non-motor features in patients with essential tremor (ET). However, the relationship of ET with cognitive impairments and affective disorders remains controversial. This meta-analysis aimed to analyze the association of ET with dementia and affective disorders.MethodsOriginal studies published from January 1999 to October 2019 were systematically searched from the database of Medline (OvidSP), EMBASE (OvidSP), and the Cochrane Central Register of Controlled Trials. Pooled standard mean difference (SMD, random effect model), odds ratios (ORs), relative risk (RR), and 95% CI were calculated.ResultsCompared with the Non-ET group, patients with ET had significantly lower Mini-Mental State Examination (MMSE) score (SMD, −1.16; 95% CI, −1.75 to −0.58; p = 0.0001) and had significantly higher depressive and anxiety symptoms scale score (SMD, 0.55; 95% CI, 0.22–0.87; p = 0.0009). The OR for dementia and affective disorders in individuals with ET compared with individuals without ET was 2.49 (95% CI, 2.17–2.85, p < 0.00001). While there was no significant difference in Montreal Cognitive Assessment (MoCA) score between ET and Non-ET groups (SMD, −0.52; 95% CI, −0.16 to 0.13; p = 0.23), there was a significant difference in the risk of mortality between ET and Non-ET groups (RR = 4.69, 95% CI, 2.18–10.07).ConclusionThe non-motor symptoms should not be neglected among patients with ET. However, the causal relationship between ET and dementia, depression, and anxiety is unclear.

The reported prevalence of abnormal findings by brain MRI varies from 11 to 83% among patients with anti-This retrospective study analyzed a consecutive series of 52 patients with anti-NMDAR encephalitis admitted to our hospital. The patients were assigned to the "MRI-normal" or the "MRI-abnormal" group based on brain MRI after admission. The groups were compared in terms of clinicodemographic characteristics and scores on the Mini-Mental State Examination (MMSE) and modified Rankin Scale (mRS) 3 and 12 months after admission.Thirty-seven (71.15%) of the patients showed abnormalities on brain MRI; these patients were more likely to be men and showed abnormalities on electroencephalography. Patients who showed normal or abnormal MRI findings did not differ significantly in terms of clinical symptoms, rates of mortality or relapse, or mRS scores after 3 and 12 months. However, patients with abnormal MRI showed significantly lower MMSE scores than those with normal MRI after 3 and 12 months.We found high prevalence of abnormal MRI findings in our sample of Chinese patients with anti-NMDAR encephalitis. We also found that the abnormal findings were associated with cognitive decline but not necessarily with mortality or functional outcomes in the short or long term.

Yueyi Yao,1 Changyan Li,1 Fusheng Qian,1 Yu Zhao,1 Xiaoyi Shi,1 Dan Hong,1 Qinglong Ai,2 Lianmei Zhong2 1Science and Technology Achievement Incubation Center, Kunming Medical University, Kunming, 650500, People’s Republic of China; 2Department of Neurology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People’s Republic of ChinaCorrespondence: Lianmei Zhong; Qinglong AiDepartment of Neurology, First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, 650032, Yunnan Province, People’s Republic of ChinaTel/Fax +86-0871-65336015Email 13888967787@163.com; aiqinglong63@163.comPurpose: Neuroinflammation runs through the whole process of nervous system diseases and brain injury. Inflammasomes are thought to be especially relevant to immune homeostasis, and their dysregulation contributes to pyroptosis. The natural compound Ginsenoside Rg1 has been shown to possess anti-inflammatory effects; however, its underlying mechanisms are not entirely clear. Therefore, this study was undertaken to investigate the role and mechanisms of Rg1 in regulating the production of inflammasomes and pyroptosis of microglia in vivo and in vitro.Methods: BV-2 microglial cells were pretreated with Rg1, stattic and interleukin-6 (IL-6), and then stimulated with lipopolysaccharide (LPS) (2μg/mL). Hoechst staining and Annexin V-FITC/PI assay were then carried out. The expression levels of cleaved-caspase-1, pro-caspase-1, interleukin-1β (IL-1β), mature-IL-1β, gasdermin D (GSDMD), activated NH(2)-terminal fragment of GSDMD (GSDMD-N), NOD-, LRR- and pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), absent in melanoma 2 (AIM2), signal transducer and activator of transcription 3 (STAT3) and phosphorylated STAT3 in BV-2 were detected by Western blotting. Additionally, immunofluorescence staining was used to determine the expression of NLRP3 and p-STAT3 in postnatal rat brain and BV-2 microglia subjected to LPS stimulation and Rg1 pretreatment. The targets of transcription factor STAT3 were predicted by hTFtarget and chromatin immunoprecipitation (ChIP) was used to confirm the interaction between STAT3 and AIM2.Results: We showed here that Rg1 effectively inhibited the expression of inflammasomes and microglia pyroptosis induced by LPS. The targets predicted data of Rg1 from Swiss target prediction database showed STAT3 had the highest thresholds of probability score. Rg1 can regulate the phosphorylation of STAT3, which binds to the promoter region of inflammasome AIM2.Conclusion: It is suggested that STAT3 signaling can initiate the transcription activity of AIM2. Rg1 regulates microglia pyroptosis in neuroinflammation induced by LPS through targeting STAT3 signaling.Keywords: neuroinflammation, AIM2, microglia, pyroptosis, Rg1

Background and Purpose: Silent brain infarct (SBI), which has traditionally been considered clinically silent, has been proposed as a subclinical risk marker for future cognitive function decline. Methods: We conducted a systematic review of literature in the Cochrane Library, MEDLINE, EMBASE, and the China National Knowledge Infrastructure database. Results: In the end, 19 case-control studies, comprising 6712 participants, and 3 prospective cohort studies comprising 4433 participants, met all inclusion criteria and were included in the systematic review. Meta-analysis of 9 studies showed that SBI was an important factor in cognitive function decline (Mini-Mental State score) (standardized mean difference −.47, 95% confidence interval; −.72 to −.22). Another meta-analysis of 4 studies reported the SBI was an independent factor in cognitive dysfunction (Montreal Cognitive Assessment Scale) (standardized mean difference −3.36, 95% confidence interval; −5.90 to −.82). Ten studies further reported that SBI was associated with decreases in specific areas of cognitive function. Conclusions: These results suggest that rather than being clinically silent, SBI might be a factor inducing cognitive dysfunction.

Microglia contribute to the regulation of neuroinflammation and play an important role in the pathogenesis of brain disorders. Thus, regulation of neuroinflammation triggered by activation of microglia has become a promising therapeutic strategy. Here, we investigated the beneficial effects of Gastrodin in activated microglia and analyzed the underlying molecular mechanisms. Microglia activation was regulated by Gastrodin not only in terms of microglia population size but also production of inflammatory mediators. Gastrodin inhibited the expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), cyclin-D1 and Ki67 in lipopolysaccharide (LPS)-stimulated BV-2 or primary microglia. Gastrodin also suppressed the expression of iNOS and Ki67 in activated microglia in three-day-old LPS-injected postnatal rats. In addition, the present results have shown that Gastrodin inhibited LPS-induced phosphorylation of glycogen synthase kinase-3β (GSK-3β) at Ser 9 and β-catenin activity. We further extended our investigation to determine whether Wnt/β-catenin signaling pathway was involved in the anti-inflammatory and anti-proliferation function of Gastrodin. β-Catenin antagonist (XAV939) was used to block LPS-mediated upregulation of iNOS, TNF-α, cyclin-D1, nitric oxide (NO) and the number of cells in the G2/M+S phase of cell cycle. Moreover, treatment with LiCl, a special Wnt/β-catenin pathway agonist significantly blocked Gastrodin-mediated down-regulation of iNOS, TNF-α, cyclin-D1, NO and the number of cells in the G2/M+S phase of cell cycle in LPS-stimulated BV-2 microglia. Taken together, the present results suggested that Gastrodin mediated anti-inflammatory and anti-proliferation effects in activated microglia by modulating the Wnt/β-catenin signaling pathway.

Neuromyelitis optica (NMO) and NMO spectrum disorders (NMOSD) have garnered attention due to their high pathogenicity, high risk of relapse, and poor prognosis as an inflammatory central nervous system (CNS) syndrome. There is a consensus that the anti-aquaporin-4 antibody (AQP4-IgG) is the main pathogen detectable in majority of NMOSD patients, including traditional NMO and AQP4-IgG-positive optic neuritis. In serum-negative NMOSD patients, myelin oligodendrocyte glycoprotein (MOG) antibodies are considered pathogenic factors. At present, patients with NMO optic neuritis (NMO-ON) hardly benefit from common therapies. A limitation of studies on NMO-ON is the inadequacy of animal models. This review article focuses on the characteristics of visual impairments in NMOSD and the application of experimental rodent models which are required for elucidating the pathology and potential treatments for NMO visual impairment.

OBJECTIVES: Diagnosis and management of essential hypertension (EH) or type 2 diabetes mellitus (T2DM) by combining comprehensive treatment and classificatory diagnosis have been continuously improved. However, understanding the pathogenesis of EH patients with concomitant T2DM and subsequent treatment remain the major challenges owing to the lack of non-invasive biomarkers and information regarding the underlying mechanisms. METHODS: Herein, we collected 200 serum samples from EH and/or T2DM patients and healthy donors (N). Gene-expression profiling was conducted to identify candidate microRNAs with clinical significance. Then, a larger cohort of the aforementioned patients and 50 N were used to identify the correlation between the tumor suppressor miR-195-5p and EH and/or T2DM. The dual-luciferase reporter assay was used to explore the target genes of miR-195-5p. The suppressive effects of miR-195-5p on the 3′-UTR of the dopamine receptor D1 (DRD1) transcript in EH patients with concomitant T2DM were verified as well. RESULTS: Compared with that in other groups, serum miR-195-5p was highly downregulated in EH patients with concomitant T2DM. miR-195-5p overexpression efficiently suppressed DRD1 expression by binding to the two 3′-UTRs. Additionally, two single nucleotide polymorphisms, including 231T-A and 233C-G, in the miR-195-5p binding sites of the DRD1 3′-UTR were further identified. Collectively, we identified the potential clinical significance of DRD1 regulation by miR-195-5p in EH patients with concomitant T2DM. CONCLUSIONS: Our data suggested that miR-195-5p circulating in the peripheral blood served as a novel biomarker and therapeutic target for EH and T2DM, which could eventually help address major challenges during the diagnosis and treatment of EH and T2DM.

Background and purpose Early prediction of stroke‐associated pneumonia (SAP) is significant in clinical practice, as it is frequently challenging due to delays in typical clinical manifestations and radiological changes. The monocyte‐to‐lymphocyte ratio (MLR) has been proposed as an indicator of systemic inflammation and infection. However, none of these studies have focused on the predictive value of the MLR for SAP. We investigated the predictive value of MLR for SAP and investigated its relationship with disease severity. Methods In this retrospective study, we assessed 399 consecutive patients with acute stroke. SAP was defined according to the modified Centers for Disease Control and Prevention criteria. The severity of pneumonia was rated using the pneumonia severity index (PSI). MLR was calculated by dividing absolute monocyte counts by absolute lymphocyte counts. Results Among all the patients, SAP occurred in 116 patients (29.1%). White blood cell (WBC), neutrophil, monocyte, and MLR levels in the SAP group were higher than those in the non‐SAP group, while lymphocyte levels were lower (p, Monocyte to lymphocyte ratio (MLR) have been proposed as indicators of systemic inflammation and infection. However, none studies have focused on the predictive value of MLR for SAP. We investigated the predictive value of MLR for SAP and to investigate their relationship with disease severity.

Background Hyperglycemia was associated with delayed cerebral infraction (DCI) and poor outcomes in aneurysmal subarachnoid hemorrhage (aSAH) patients. However, the influence of glucose fluctuation on DCI and mortality in aSAH patients was still unclear. Objective This study aimed to clarify the relationship of glucose fluctuation and DCI occurrence or 30 days mortality in aSAH patients who were admitted in Neurocritical Unit (NCU). Methods A total of 341 patients with aSAH were retrospectively recruited and studied. Continuous 14-day fasting blood glucose was collected and divided into four groups: stable, unstable, well-controlled, bad-controlled. Risk factors that were associated with glucose fluctuation, DCI occurrence and 30 days mortality was analyzed.Results Many risk factors, such as Age (59.09±11.95), Diabetes history, SBP (162.91±20.85), BUN (5.50±1.80), HA1c (7.12±1.65), BGV (0.32±0.11), Hunt-Hess Score (2.59±0.97), GCS Score (10.68±4.23), Hydrocephalus in Forth ventricle, Third ventricle and Lateral ventricles, are associated with glucose fluctuation. Bad controlled group has the highest mortality (15.91%), then unstable (13.04%), well-controlled (6.45%), and stable group (1.42%). The unstable group has the highest incidence of DCI (39.13%), then bad-controlled (29.55%), the stable (17.92%) and well-controlled (17.74%). Conclusions Unstable and bad-controlled glucose during NCU admission was associated with DCI and 30 days mortality of aSAH patients.

Microglia-mediated neuroinflammation is known to play a pivotal role in the pathogenesis of different neurological diseases. Gastrodin, a phenolic glucoside, has been reported to exert anti-inflammatory effects in activated microglia challenged with lipopolysaccharide (LPS); however, the underlying mechanism has remained obscure. The present study aimed to ascertain if Gastrodin would regulate the Notch signaling pathway involved in microglia activation. We show here that LPS increased the expression of various members of the Notch-1 pathway, including intracellular Notch receptor domain (NICD), recombining binding protein suppressor of hairless (RBP-Jκ) and transcription factor hairy and enhancer of split-1 (Hes-1) in microglia in postnatal rat brain and in BV-2 microglia. Remarkably, Gastrodin was found to markedly attenuate the expression of the above various biomarkers both in vivo and in vitro. Moreover, increased phosphorylation level of ERK, JNK and P38 induced by LPS was attenuated with pretreatment of Notch-1 signaling inhibitor, N-[N-(3,5-difluorophenacetyl)-1-alany1-Sphenyglycinet-butylester (DAPT) as well as Gastrodin. Gastrodin mimicked the effects of DAPT by inhibiting the LPS-induced expression of IL-1β, IL-6, IL-23, TNF-α and NO. Moreover, lentivirus transfection mediated NICD overexpression inhibited the anti-inflammatory effects of Gastrodin. Furthermore, the activation of Notch-1 signaling promoted microglia migration and Gastrodin could inhibit the migration of activated BV-2 microglia by regulating the Notch-1 signaling pathway. In light of the above, our results indicate that Notch-1 signaling pathway is involved in the anti-inflammatory effects of Gastrodin against LPS-induced microglia activation. These findings provide a new biological target of Gastrodin for the treatment of neuroinflammatory disorders.

Objective This study examined the clinical features, functional outcomes, and prognostic indicators of acute ischemic stroke (AIS) patients who had an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) ≤ 5 and who underwent mechanical thrombectomy (MT). Methods We included consecutive AIS patients with ASPECTS ≤ 5 who had received MT at the same hospital. Demographic, clinical, and radiological data were collected and analyzed. Functional outcome at 90 days after treatment was classified as good or poor based on the modified Rankin Scale (mRS). Results Of the 152 included patients with ASPECTS ≤ 5 who received MT, 64 (42.11%) experienced poor functional outcomes and 32 (21.1%) experienced good functional outcomes. The independent predictors of poor functional outcomes were the presence of respiratory tract infections (OR 3.72, 95% CI 1.17–11.91), modified thrombolysis in cerebral infarction (OR 0.41, 95% CI 0.2–0.83), symptomatic intracerebral hemorrhage (sICH) (OR 4.96, 95% CI 1.36–18.13), and baseline score on the National Institute of Health Stroke Scale (NIHSS) (OR 1.18, 95% CI 1.03–1.36). Independent predictors of 90-day mortality included time from groin puncture to recanalization (OR 1.03, 95% CI 1.01-1.05), NIHSS scores (OR 1.28, 95% CI 1.12–1.47) and the occurrence of sICH (OR 1.81, 95% CI 1.25-5.75). Conclusion AIS patients with ASPECTS ≤ 5 can experience good functional outcomes after MT. However, patients with sICH, respiratory infection, higher NIHSS score or failed recanalization are more likely to experience poor functional outcomes.

The “spot sign” is a well-known radiological marker used for predicting hematoma expansion and clinical outcomes in patients with intracerebral hemorrhage (ICH). We performed a meta-analysis to assess the predictive accuracy of spot sign, depending on the criteria used to identify them. We conducted a systematic review of clinical studies that clearly stated their definition of spot sign and that were indexed in the Cochrane Library, MEDLINE, EMBASE, and the China National Knowledge Infrastructure databases. We collected data on computed tomography (CT) parameters, spot sign diagnostic criteria, hematoma expansion, and clinical outcomes. Based on the eligibility criteria, we included 17 studies in this systematic review. CT imaging modality, type, time from symptom onset to CT, time from contrast infusion to scan, slice thickness, tube current, and tube electric discharge showed variation across studies. Three different definitions of the spot sign were applied: (1) a hyperdense spot within the hematoma; (2) one or more focal areas/regions of contrast pooling of any size and morphology that occurred within a hemorrhage, were discontinuous from the normal or abnormal vasculature adjacent to the hemorrhage, and showed an attenuation rate ≥ 120 UH; or (3) serpiginous or spot-like contrast density on CTA images that occurred within the hematoma margin, showed twice the density of the hematoma background, and did not contact vessels outside the hematoma. Three definitions for the spot sign were identified, all of which were associated with hematoma expansion, mortality, and unfavorable functional outcome. Subgroup analyses based on these definitions showed that spot sign identified using the second definition were more likely to be associated with hematoma expansion (OR 18.31, 95% CI 9.11–36.8) and unfavorable functional outcomes (OR 8.78, 95% CI 3.24–23.79), while those identified using the third definition were associated with increased risk of mortality (OR 6.88, 95% CI 1.43–33.13). Clinical studies identify spot sign using different CT protocols and criteria. These differences affect the ability of spot sign to predict hematoma expansion and clinical outcomes in ICH patients.

Microglia mediated neuroinflammation is known to cause various neurodegenerative and neurological ailments. Tannic acid is a natural polyphenol which has been reported to possess antioxidant, anti-inflammatory, anticarcinogenic, antimutagenic, antitumor, and antimicrobial activities. As there are no reports till date on the anti-neuroinflammatory effects of tannic acid, this study was conducted to analyze the possible mechanism and pathway involved in the prevention of neuroinflammation by tannic acid in BV2 microglial cells. BV2 microglial cells were pretreated with tannic acid (10, 25, and 50 μM/mL) and induced with lipopolysaccharide (LPS; 1 μM/mL) to assess the production of reactive oxygen species (ROS), nitric oxide (NO), prostaglandin E2 (PGE2), pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), and nuclear factor-kappa B (NF-κB) protein expressions through western blotting. The results showed that LPS significantly activated the BV2 cells via toll-like receptor 4 to induce elevated productions of ROS, NO, PGE2, IL-6, and IL-1β. However, tannic acid was able to reverse all the neuroinflammatory effects of LPS-induced BV2 cells in a dose-dependent manner. Collectively, the anti-inflammatory effects of tannic acid on LPS-induced BV2 microglial cells are attributed to the inhibition of ROS formation and the suppression of NF-κB pathway activation. Tannic acid could be a potential therapeutic agent for the treatment of neurological related disorders.

Neuromyelitis optica (NMO) and NMO spectrum disorder (NMOSD) are inflammatory CNS syndromes mainly involving the optic nerve and/or spinal cord and characterized by the presence of serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). The pathology of NMOSD is complicated, while therapies for NMOSD are limited and only partially effective in most cases. This review article focuses on the main pathology of NMOSD involving AQP4-IgG and lymphocyte function. We also review the existing therapeutic methods and potential new treatments. Experimental NMO animal models are crucial for further research into NMO pathology and treatment. However, no AQP4-IgG-immunized animals have been reported. The establishment of NMO models is therefore difficult and primarily depends on the generation of transgenic mice or transcranial manipulation using human or monoclonal mouse anti-AQP4 antibodies. Advantages and disadvantages of each model are discussed.

Leptin may be associated with cardiovascular disease. We tested to determine whether leptin is a marker for first-ever acute ischemic stroke (AIS) in a nested case-referent study.Consecutive patients with first-ever AIS from May 2017 to December 2017 were included. Referents were matched for sex, age and body mass index. Serum leptin levels and routine tests were examined in both groups.The median serum level of leptin in the stroke patients was 14.3 (interquartile range [IQR], 7.2-21.7) ng/ml, which was significantly higher (P 0.001) than in the referents (10.7; 5.7-13.6 ng/ml). There was a positive correlation between serum level of leptin and National Institute of Health Stroke Scale score (r[Spearman] = 0.43, P 0.001). In addition, serum leptin levels paralleled lesion size. Median serum level of leptin in patients with small lesions, medium lesions and large lesions was 7.3 (IQR, 5.3-14.3) ng/ml, 13.9 (IQR, 7.0-21.3) ng/ml, 20.5 (IQR, 12.4-32.7) ng/ml, respectively (analysis of variance: P 0.001). In the univariate model matching for sex and age, leptin as a continuous variable was associated with AIS, after adjustment for possible confounders (odds ratio [OR] 1.07, 95% confidence interval [CI]: 1.04-1.11; P 0.001). After adjusting for all other factors, leptin remained an independent stroke predictor with an adjusted OR of 1.03 (95% CI, 1.00-1.10; P = 0.006). Interestingly, the association between AIS and leptin level was more pronounced among men (adjusted OR = 1.05, 95% CI: 1.01-1.12; P 0.001) when compared with women (adjusted OR = 1.03, 95% CI: 1.10-1.11; P = 0.009).Serum leptin is associated with first-ever AIS, lesion size and stroke severity in a Chinese cohort.

Scaffolds are used in tissue engineering to provide a temporary structural template for cell colonization and matrix formation. Here, an emerging polyurethane (PU) porous scaffold incorporated with renewable gastrodin was developed, and its mechanical properties and cell behavior were evaluated. The results showed that the scaffold had an interconnected porous structure, the chemical modification of PU by 8.99 wt% gastrodin synergistically enhanced initial modulus by 222% and porosity by 63%; the stem cells seeded on such scaffold exhibited higher cytocompatibility, the proper pore size was favorable for cell attachment and proliferation compared to the scaffold without gastrodin. This study for the first time demonstrates that gastrodin can chemically-polymerized onto the polyurethane matrix, improving mechanical properties and cell activity. The findings in this study highlight that this scaffold holds great promise in regenerative medicine.

Background and Purpose: There are debates about the causative role of high blood glucose in cerebral small vessel disease. The relationship between cerebral microbleeds (CMBs) and blood glucose is unclear. Methods: Patients admitted to our department with acute ischaemic stroke were consecutively and prospectively included. Baseline demographic and clinical covariates were collected and analyzed according to the occurrence and location of CMBs and levels of blood glucose. Results: Of 161 patients included in the final analysis, 69 (42.76%) were women. A total of 80 patients (49.69%) had CMBs. There was a significant trend towards the prevalence of CMBs with increasing glucose quarter (p = 0.001). Post hoc analysis showed the rate of prevalence of CMBs to be significantly higher in the third quarter (OR 1.90, 95% CI 1.20–3.02) and fourth quarter (OR 1.65, 95% CI 1.21–2.25) than that in the first. The frequencies of deep or infratentorial CMBs differed with glucose quarter. Post hoc analysis showed that frequencies of deep or infratentorial CMBs were significantly more frequent in the third quarter (OR 1.76, 95% CI 1.06–2.87) and fourth quarter (OR 1.65, 95% CI 1.19–2.31) than those in the first. Conclusions: In this prospective study of patients with acute ischaemic stroke, our results showed that glucose was associated with deep or infratentorial CMBs but not with lobar CMBs.

Background: Aneurysm subarachnoid hemorrhage (aSAH) is a life-threatened disease. Stress responded hyperglycemia following aSAH was one of most important predictors that was associated with poor outcomes and higher mortality of patients critically suffered from aSAH. Thus, optimal glucose management strategy could improve outcomes of aSAH patients in Neurocritical Care Unit (NCU). However, it’s still lacks of evidence on glucose level which is beneficial for severe aSAH patients. Recently, glucose variability (GV) was not only used to predict clinical outcomes and mortality, but also used as a more appropriated clinical target than blood glucose range only to manage glucose level. Our study aimed to find a relatively suitable glucose control for aSAH patients in NCU. Method: 332 patients were recruited from a retrospectively collected database of all patients with aneurysm SAH (aSAH) who were admitted to Tiantan Hospital in Beijing, China between January 2015 and December 2017. We collected continuous 14-day blood glucose and calculated glucose variability. Continuous 14-day blood glucose level were divided into four groups: stable, unstable, well-controlled, bad-controlled. Other predictor variables also included admission Hunt and Hess grade, age, gender, cardiovascular risk factors, and surgical treatment. In-patient mortality was the main outcome measure. Results: Univariate survival analysis showed that the stable and well-controlled groups have higher percentage of cumulative survival than the rest two groups. Then, Multivariate COX regression analysis showed that Hunt Hess scale (HR 2.666, 95% CI, 1.438-4.944), receiving Surgery (HR 0.073, 95% CI, 0.025-0.219), having hydrocephalus (HR 3.844, 95% CI, 1.038-14.228), bleeding in cisterna ambiens (HR 8.288, 95% CI, 2.270-30.259),bad-controlled glucose (HR 5.788, 95% CI, 1.441-23.237) and unstable glucose (HR 15.403, 95% CI, 2.666-88.987). Conclusions: GV is helpful to predict aSAH mortality, either long-term or short-term. Glucose fluctuated between 7 and 10 mmol/L is associated with better 14-day clinical outcomes for critically ill aSAH patients in NCU. Funding Statement: None. Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: This retrospective study was approved by the Ethics Committee at the Tiantan Hospital in Beijing, in accordance with the Declaration of Helsinki; patient informed consent was not required because of the anonymous nature of the data.

High-mobility group box 1 (HMGB1) and advanced glycation end-products (RAGE) are potential mediators of inflammation. We investigate the association between levels of HMGB1 and soluble RAGE (sRAGE) following intracerebral hemorrhage (ICH) and the severity of ICH. There was a significant trend towards higher poor functional outcome rate with increasing HMGB1 and sRAGE tercile. The correlation analysis indicated that the levels of HMGB1and sRAGE were positively correlated with hematoma volume. The receiver operating curve (ROC) was 0.718 for HMGB1 and 0.631 for sRAGE to poor functional outcome. HMGB1 and sRAGE quantification provides more accurate prognostic information after ICH.

This study was aimed to determine Gastrodin (GAS) and its underlying signaling pathway involved in suppression of inflammasome specifically in reactive astrocytes that are featured prominently in different neurological conditions or diseases including cerebral ischemia. For this purpose, TNA2 astrocytes in cultures were exposed to oxygen–glucose–deprivation (OGD) mimicking hypoxic cerebral ischemia. Separately, TNA2 cells were pretreated with GAS prior to OGD exposure. Additionally, Stattic, an inhibitor of STAT3 signaling pathway, was used to ascertain its involvement in regulating inflammasome in astrocytes exposed to OGD. In parallel to the above, adult rats subjected to middle cerebral artery occlusion (MCAO) with or without GAS pretreatment were sacrificed at different time points to determine the effects of GAS on astrocyte inflammasome. TNA2 astrocytes in different treatments as well as reactive astrocytes in MCAO were processed for immunofluorescence labeling and Western blot analysis for various protein markers. In the latter, protein expression levels of p-STAT3, NLRP3, and NLRC4 were markedly increased in TNA2 astrocytes exposed to OGD. Remarkably, the expression levels of these biomarkers were significantly suppressed by GAS. Of note, GAS especially at dose 20 μM inhibited NLRP3 and NLRC4 expression levels most substantially. Moreover, GAS inhibited the downstream proteins caspase-1 and IL-18. Concomitantly, GAS significantly suppressed the expression of STAT3 and NF-κB signaling pathway. It is noteworthy that Stattic at dose 100 μM inhibited STAT3 pathway and NF-κB activation in TNA2 astrocytes, an effect that was shared by GAS. In MCAO, GAS was found to effectively attenuate p-STAT3 immunofluorescence intensity in reactive astrocytes. Arising from the above, it is concluded that GAS is anti-inflammatory as it effectively suppresses inflammasome in OGD-stimulated astrocytes as well as in reactive astrocytes in MCAO via STAT3 and NF-κB signaling expression coupled with decreased expression of caspase-1 and IL-18.

Brain damage, including blood-brain barrier (BBB) dysfunction, neurological behavior deficit, cerebral infarction and inflammation, is commonly caused by ischemic-reperfusion (I/R) injury. Prevention of the above biological process defects is considered beneficial for patient recovery after I/R injury. This study was aimed to assess the neuroprotective effect of Gastrodin (GAS), an herbal agent, in experimentally induced cerebral ischemia. Sprague-Dawley adult rats were randomly divided into six groups: Sham-operated control group (Sham), middle cerebral artery occlusion (MCAO) group, GAS (50, 100, and 200 mg/kg) pretreatment + MCAO groups (GAS) and Nimodipine (NIM) + MCAO, namely, the NIM group. Additionally, an OGD/R model using BV-2 microglia was established in vitro to simulate I/R injury. We showed here that the neurological scores of rats in the GAS groups were significantly improved compared with the MCAO group. Moreover, the area of cerebral infarction in the GAS pretreatment groups and the NIM group was significantly reduced. Furthermore, Evans blue leakage volume was significantly reduced with GAS pretreatment notably at dose 100 mg/kg. Expression of matrix metalloproteinase 2 (MMP2) and MMP9 in GAS groups was markedly decreased when compared with MCAO group. In BV-2 microglia exposed to OGD/R given GAS pretreatment, MMP2 and MMP9 positive cells were reduced in numbers. The present results have shown that GAS pretreatment significantly compensated for neurological behavior defects in rats with I/R-induced injury, reduced brain infarction size, reversed BBB impairment, and attenuated inflammation. It is suggested that pretreatment with GAS before surgery is beneficial during recovery from I/R injury.

BACKGROUND Keloid is a common abnormal cutaneous fibroproliferative disorder. However, the process underlying keloid pathogenesis still remains to be unclear. OBJECTIVE To integrated analyse the miRNA expression profiles of keloid. METHODS We performed miRNA expression profiles analysis of 3 paired keloid and normal tissue samples by miRNA microarray. Differentially expressed miRNAs were further performed integrative analysed and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). After predicting target genes, we constructed the miRNA-target genes interaction network and carried out bioinformatics analysis. RESULTS The results revealed that 264 miRNAs were significantly altered. The expression of high frequency miRNAs which included miRNA-199a-5p, miRNA-21-5p, miRNA-214-5p, miRNA-424-5p, and miRNA-205-5p was further evaluated. The gene ontology (GO) analyses and the top enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed these target genes were associated with MAPK signaling pathway and HIF-1 signaling pathway. CONCLUSION This study revealed the profiling of miRNAs in keloid that are potentially implicated in the development of this disease and could serve as novel diagnostic and therapeutic target of keloid.

Background Essential hypertension (EH) is one of the major cardiovascular diseases. Recent studies demonstrated that dopamine D1 and D3 receptor gene polymorphisms (DRD1 and DRD3) play an important role in EH. Material/Methods To investigate whether DRD1 and DRD3 polymorphisms are associated with EH, 3 single-nucleotide polymorphisms (SNPs) of the DRD1 and 6 SNPs of DRD3 gene were analyzed in 3 ethnic groups. SNPStats was used to obtain odds ratios (ORs), 95% confidence intervals (CIs), and P values. Multiple logistic regression models (co-dominant, dominant, recessive, over-dominant, and log-additive) and chi-squared test were conducted to analyze the genetic data by chi-squared test. Results Synonymous SNPs (rs1799914 and rs4867798) of the DRD1 gene and SNPs (rs9880168) of the DRD3 were associated with EH in Hani nationality (OR 3.77, 0.63, 1.43, 5.00, respectively; 95% CI 1.05–13.54, p=0.024; 0.44–0.90, p=0.0121; 1.06–1.94, p=0.019; 1.08–23.10, p=0.017, respectively; Recessive, over-dominant model, respectively). However, none SNPs of DRD1 and DRD3 of best models showed association with EH in Han and Yi nationality. Conclusion These results suggest that SNPs of DRD1 and DRD3 may be contributed to essential hypertension in Hani nationality of China.