Current Neurovascular Research - Volume 17, Issue 4, 2020

Background and Purpose: Hemorrhagic transformation (HT) has an adverse effect on the prognosis of patients with acute ischemic stroke, and it is currently known associated with coagulation system. But the conclusion is not consistent and remains to be identified. The aim of this study was to investigate the association between coagulation function and spontaneous hemorrhagic transformation. Methods: Patients within 7 days from the onset of ischemic stroke who did not receive reperfusion therapy (thrombolysis or endovascular treatment) were included between January 2016 and October 2017. Coagulation function indicators, including prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), thrombin time (TT) and fibrinogen (FIB), were tested within 24 h after admission. HT was defined as hemorrhage presented on follow-up magnetic resonance imaging (MRI) or computed tomography (CT) but not on baseline CT. We performed binary logistic regression to examine the association between coagulation function and HT. The coagulation indicators were entered into logistic regression analysis as continuous variables (per 1-unit/L increase) and four-categorized variables (with data collapsed into quartiles), respectively. Results: A total of 1141 patients were included (mean age, 64 ± 15 years; 63.7% males). 102 patients experienced HT (8.9%), of whom 14 patients experienced symptomatic HT (sHT, 1.2%). After adjustment for confounders, TT in the highest quartile is inversely associated with risk of HT (as continuous variable, odds ratio [OR] 0.85; 95% confidence level [CI] 0.73-0.99, P = 0.042; as four-categorized variable, OR 0.36, 95% CI 0.18 - 0.7, P = 0.003). Whether as continuous variables or four-categorized variables, PT, INR, APTT and FIB had no association with HT. Conclusion: Not the whole process of coagulation function is associated with spontaneous HT. Prolonged TT, which may indicate an extension of the last step of the coagulation process, is independently and inversely associated with spontaneous HT in patients with acute ischemic stroke.

Background: Patients with temporal lobe epilepsy (TLE) usually suffer from cognitive deficits and recurrent seizures. Brivaracetam (BRV) is a novel anti-epileptic drug (AEDs) recently used for the treatment of partial seizures with or without secondary generalization. Different from other AEDs, BRV has some favorable properties on synaptic plasticity. However, the underlying mechanisms remain elusive. Objective: The aim of this study was to explore the neuroprotective mechanism of BRV on synaptic plasticity in experimental TLE rats. Methods: The effect of chronic treatment with BRV (10 mg/kg) was assessed on Pilocarpine induced TLE model through measurement of the field excitatory postsynaptic potentials (fEPSPs) in vivo. Differentially expressed synaptic vesicle protein 2A (SV2A) were identified with immunoblot. Then, fast phosphorylation of synaptosomal-associated protein 25 (SNAP-25) during long-term potentiation (LTP) induction was performed to investigate the potential roles of BRV on synaptic plasticity in the TLE model. Results: An increased level of SV2A accompanied by a depressed LTP in the hippocampus was shown in epileptic rats. Furthermore, BRV treatment continued for more than 30 days improved the over-expression of SV2A and reversed the synaptic dysfunction in epileptic rats. Additionally, BRV treatment alleviates the abnormal SNAP-25 phosphorylation at Ser187 during LTP induction in epileptic ones, which is relevant to the modulation of synaptic vesicles exocytosis and voltagegated calcium channels. Conclusion: BRV treatment ameliorated the over-expression of SV2A in the hippocampus and rescued the synaptic dysfunction in epileptic rats. These results identify the neuroprotective effect of BRV on TLE model.

Background: It is unknown if improvements in ischemic stroke (IS) outcomes reported after cerebral reperfusion therapies (CRT) in developed countries are also applicable to the “real world” scenario of low and middle-income countries. We aimed to measure the long-term outcomes of severe IS treated or not with CRT in Brazil. Methods: Patients from a stroke center of a state-run hospital were included. We compared the survival probability and functional status at 3 and 12 months in patients with severe IS treated or not with CRT. From 2010 to 2011, we performed intravenous reperfusion when patients arrived within 4.5 h time-window (IVT group) and after 2011, mechanical thrombectomy (MT) combined or not with intravenous alteplase (IAT group). Those who arrived >4.5 h in 2010-2011 and >6 h in 2012-2017 did not undergo CRT (NCRT group). Results: From 2010 to 2017, we registered 917 patients: 74% (677/917) in the NCRT group, 19% (178/917) in the IVT group and 7% (62/917) in the IAT group. Compared to the NCRT group, IVT patients had a 28% higher (HR: 0.72; 95% CI 0.53-0.96) 3-month adjusted probability of survival and risk of functional dependence was 19% lower (adjusted RR: 0.81; 95% CI 0.73-0.91). For those who underwent MT, the adjusted probability of survival was 59 % higher (HR: 0.41; 95% CI 0.21-0.77) and the risk of functional dependence was 21% lower (adjusted RR: 0.79; 95% CI 0.66-094). These outcomes remained significantly better throughout the first year. Conclusion: CRT led to better outcomes in patients with severe IS in Brazil.

Objective: This study evaluated the relationship between HbA1c (glycated hemoglobin), admission serum glucose levels and outcomes in patients with large artery occlusion (LAO) treated with mechanical thrombectomy (MT). Methods: A total of 413 patients were enrolled, and the following outcomes were reviewed: successful recanalization, symptomatic hemorrhage, favorable outcome (modified Rankin Scale, mRS scores of 0-2), and mortality at 3 months. Receiver operating characteristic (ROC) curve analysis was undertaken to identify the cutoff values for HbA1C and glucose to discriminate between favorable and unfavorable outcomes. The association of HbA1c and glucose levels with outcomes was evaluated using logistic regression. Results: The best cutoff values to discriminate between favorable and unfavorable outcome after 3 months were identified by an HbA1C value of 6.0% and an admission serum glucose level of 131 mg/dL (P = <0.001 and <0.001, respectively). Patients with HbA1C ≥6.0% had a lower ratio of favorable mRS, more symptomatic hemorrhage, and higher mortality than those of HbA1C<6.0% (P = 0.002, 0.001, and <0.001, respectively). In multivariate analysis, high HbA1C (≥6.0%) and serum glucose on admission (≥131 mg/dL) were significantly associated with unfavorable outcomes at 3 months (P = 0.006 and 0.009, respectively). Conclusion: This study demonstrated that patients with HbA1C ≥% had more unfavorable 3- month mRS, higher symptomatic hemorrhage, and a higher degree of mortality than those with HbA1C <6.0%. Higher HbA1C and admission serum glucose levels are independent predictors of unfavorable clinical outcomes in LAO patients treated with MT.

Background: Serum albumin level is associated with infection after stroke, but whether albumin predicts post-stroke pneumonia is unclear. The potential relationship between albumin level and pneumonia in patients with acute ischemic stroke (AIS) was evaluated in this study. Methods: A consecutive sample of 798 AIS patients who were admitted to West China Hospital within 24 h after onset, from the year 2017 to 2018, were retrospectively analyzed. Blood was collected on admission and assayed for serum albumin. Univariate analyses, multivariate logistic regression, and stratified logistic regression were performed to identify the risk factors of post-stroke pneumonia. Results: Out of the 798 patients, 240 (30.2%) developed pneumonia at a median of 48 h after onset (interquartile range, 27-74 h). Patients with pneumonia had significantly lower serum albumin levels than those without pneumonia (40.6 vs. 42.9 g/l, p<0.001). After adjustment, the albumin level was still significantly associated with pneumonia in multivariate logistic regression (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.81-0.94). The association between serum albumin and pneumonia tended to depend on National Institutes of Health Stroke Scale score (p = 0.045), but this was significant only in patients with mild stroke (OR 0.84, 95% CI 0.77-0.93). A dosedependent inverse relationship was found between albumin levels and the risk of pneumonia after AIS. Albumin values predicted pneumonia with an area under the curve of 0.661 (95% CI 0.620- 0.701), and the optimal cutoff was 42.6 g/L. Conclusion: Low serum albumin levels may be independent predictors of pneumonia in patients with AIS, especially in mild stroke. In fact, the risk of pneumonia may vary inversely with albumin level.

Background: Ischemia/reperfusion (I/R) injury involves complex biological processes and molecular mechanisms such as autophagy. Oxidative stress plays a critical role in the pathogenesis of I/R injury. LncRNAs are the regulatory factor of cerebral I/R injury. Methods: This study constructs cerebral I/R model to investigate role of autophagy and oxidative stress in cerebral I/R injury and the underline regulatory mechanism of SIRT1/ FOXO3a pathway. In this study, lncRNA SNHG12 and FOXO3a expression was up-regulated and SIRT1 expression was down-regulated in HT22 cells of I/R model. Results: Overexpression of lncRNA SNHG12 significantly increased the cell viability and inhibited cerebral ischemicreperfusion injury induced by I/Rthrough inhibition of autophagy. In addition, the transfected p-SIRT1 significantly suppressed the release of LDH and SOD compared with cells co-transfected with SIRT1 and FOXO3a group and cells induced by I/R and transfected with p-SNHG12 group and overexpression of cells co-transfected with SIRT1 and FOXO3 further decreased the I/R induced release of ROS and MDA. Conclusion: In conclusion, lncRNA SNHG12 increased cell activity and inhibited oxidative stress through inhibition of SIRT1/FOXO3a signaling-mediated autophagy in HT22 cells of I/R model. This study might provide new potential therapeutic targets for further investigating the mechanisms in cerebral I/R injury and provide.

Objective: The aim of this investigation was to examine the association of hsCRP (highsensitivity C-reactive protein) with outcomes and prognosis of patients who underwent mechanical thrombectomy (MT) for large vessel occlusion (LVO) after acute ischemic stroke (AIS). Methods: A total of 404 patients were enrolled, and outcomes included unfavorable clinical outcome at three months (modified Rankin Scale, mRS scores 3-6), the occurrence of symptomatic intracerebral hemorrhage (sICH) and hemorrhagic transformation (HT) of the infarct. Receiver operating characteristic (ROC) curve analysis was performed to identify the cutoff value of hsCRP to discriminate between favorable and unfavorable outcomes. The association of hsCRP with outcomes was evaluated using a logistic regression model. Results: The best cutoff value of hsCRP to distinguish between favorable and unfavorable outcomes at three months was identified as 3.0 mg/L (area under the curve, [AUC] 0.641, 95% confidence interval, [CI] 0.535-0.748; P = 0.014). In, multivariate analysis, patients with hsCRP ≥3 mg/L had more unfavorable outcome (odds ratio [OR] 1.72, 95% CI 1.42-2.02; P = 0.010), sICH (OR 2.64, 95% CI 1.62-3.66; P = 0.004), and HT of infarct (OR 1.72, 95% CI 1.42-2.02; P = 0.008) compared to those with hsCRP <1 mg/L. Conclusion: Our study demonstrates that patients with higher CRP levels had more unfavorable outcome, and exhibited higher sICH, and HT of infarct than those with lower CRP levels. Elevated hsCRP level, especially when higher than 3 mg/L, is an independent predictor for poor clinical prognosis in patients with MT for LVO.

Background and Purpose: Platelet-to-neutrophil ratio (PNR) was suggested to be an independent protective predictor for 90-days outcomes in acute ischemic stroke (AIS) patients in previous studies. This study aims to investigate the association between PNR and outcomes of AIS in intravenous thrombolysis (IVT) group. Methods: Data on acute ischemic stroke patients who received intravenous thrombolysis from April 2015 to March 2019 were collected. We defined the PNR value at admission as pre-IVT PNR and after IVT within 24 h was defined as post-IVT PNR. Clinical outcome indicators included early neurological deterioration (END), hemorrhagic transformation (HT), delayed neurological deterioration (DND), and poor 3-month outcome (3m-mRS >2). Results: A total of 581 patients were enrolled in the final analysis. The age was 61(53-69) years, and 423(72.8%) were males. Post-IVT PNR was independently associated with hemorrhagic transformation (OR = 0.974; 95%CI = 0.956-0.992; P=0.006), early neurological deterioration (OR = 0.939; 95%CI = 0.913-0.966; P = 0.01), delayed neurological deterioration (OR = 0.949; 95%CI = 0.912- 0.988; P = 0.011), and poor outcome (OR = 0.962; 95%CI = 0.948-0.976; P<0.001). PNR level was identified as high (at the cut-off value or above) or low (below the cut-off value) according to receiver operating curve (ROC) analyses on each endpoint. Comparison of early neurological deterioration, hemorrhagic transformation, delayed neurological deterioration, and poor 3-month outcome (3m-mRS >2) between patients at high and low levels for platelet-to-neutrophil ratio (PNR) showed statistical differences (p<0.001). Conclusion: Post-IVT PNR was independently associated with early neurological deterioration, hemorrhagic transformation, delayed neurological deterioration, and poor 3-month outcome. Lower PNR can predict a worse outcome.

Objective: This study was conducted to evaluate the effects of anti-vascular endothelial growth factor (VEGF) antibody (bevacizumab) on vascular leakage and fibrosis in a monkey choroidal neovascularization (CNV) model. The relationship between fibrotic tissue and subretinal hyper-reflective material (SHRM), in optical coherence tomography (OCT) images, was also investigated. Methods: Experimental CNV was induced in male cynomolgus monkeys by laser photocoagulation. Intravitreal injection of bevacizumab at 0.5 mg/eye/dosing was initiated 2 weeks before or after laser irradiation and thereafter, conducted intermittently at 2- or 3-week intervals. Fluorescein fundus angiography (FA) and OCT imaging were conducted weekly from 2 to 7 weeks after laser irradiation. CNV leakage was evaluated by an established grading method using FA images. To assess the fibrosis and scarring, Masson’s trichrome specimens of each CNV lesion were prepared, and morphometric analysis was conducted using an image analysis software. Results: The effects of bevacizumab on vascular leakage were shown using an established evaluation method. Morphometric analysis of Masson’s trichrome-stained (MT) specimens revealed that collagen fiber synthesis was suppressed by bevacizumab pre-treatment (-29.2%) or post-treatment (-19.2%). SHRM was detected in OCT images in a monkey CNV model, and a significant correlation between the SHRM area in the OCT images and the collagen fiber area in the MT specimens was noted. Conclusion: In the established cynomolgus monkey CNV model, bevacizumab prevented blood leakage but could not completely suppress fibrosis. SHRM in the OCT images reflected retinal fibrous tissue in a laser-induced CNV monkey model. This model might be useful for elucidating the pathology and development therapy for neovascularization or fibrosis.

Introduction: Malignant brain edema (MBE) is a life-threatening complication for patients with large hemispheric infarction (LHI). Stroke-related inflammatory responses may cause secondary brain injury and lead to brain edema. The neutrophil to lymphocyte ratio (NLR) is a well-known systemic inflammatory biomarker. The aim of this study was to evaluate if NLR is associated with MBE in patients with LHI. Methods: A retrospective analysis was performed of LHI patients within 24 h from stroke onset admitted to the Department of Neurology, West China Hospital from January 1, 2017 to December 31, 2018. Blood samples were collected upon admission. MBE was diagnosed by any neurological deterioration accompanied by brain edema in follow-up images. Patients were categorized according to NLR tertiles. Univariate analyses were performed to identify potential confounding variables and a multivariate logistic regression analysis was conducted to determine the correlation between NLR and MBE. Results: A total of 257 patients with a mean age of 68.6 ± 14.0 years were identified. Among them, 83 (32.3%) patients developed MBE with a median time of one day (interquartile range [IQR] 0-2 days) from hospital admission. An elevated NLR was related to an increased risk of MBE when the lowest and highest tertiles were compared (odds ratio 2.27, 95% confidence interval 1.11-4.62, p = 0.024). The risk of MBE increased with the increase of NLR in a dosedependent manner (p for trend = 0.029). No interaction between potential modifiers and NLR on MBE was observed. Conclusions: Higher NLR was associated with an increased risk of MBE in patients with LHI.

Background: Limited studies concern the influence of obesity-induced dysregulation of adipokines in functional recovery after stroke neurorehabilitation. Objective: To investigate the relationship between serum leptin, resistin, and adiponectin and functional recovery before and after neurorehabilitation of obese stroke patients. The adipokine potential significance as prognostic markers of rehabilitation outcomes was also verified. Methods: Twenty obese post-acute stroke patients before and after neurorehabilitation and thirteen obese volunteers without-stroke, as controls, were examined. Adipokines were determined by commercially available enzyme-linked immunosorbent assay (ELISA) kits. Functional deficits were assessed before and after neurorehabilitation with the Barthel Index (BI), modified Rankin Scale (mRS), and Functional Independence Measure (FIM). Results: Compared to controls, higher leptin and resistin values and lower adiponectin values were observed in stroke patients before neurorehabilitation and no correlations were found between adipokines and clinical outcome measures. Neurorehabilitation was associated with improved scores of BI, mRS, and FIM. After neurorehabilitation, decreased values of Body Mass Index (BMI) and resistin together increased adiponectin were detected in stroke patients, while leptin decreased but not statistically. Comparing adipokine values assessed before neurorehabilitation with the outcome measures after neurorehabilitation, correlations were observed for leptin with BI-score, mRS-score, and FIM-score. No other adipokine levels nor BMI assessed before neurorehabilitation correlated with the clinical measures after neurorehabilitation. The forward stepwise regression analysis identified leptin as prognostic factor for BI, mRS, and FIM. Conclusion: Our data show the effectiveness of neurorehabilitation in modulating adipokines levels and suggest that leptin could assume the significance of biomarker of functional recovery.

Background: Dynamin-related protein 1 (DRP1) is a GTPase involved in mitochondrial fission, mitochondrial protein import, and drug sensitivity, suggesting an association with cancer progression. This study was conducted to evaluate the prognostic significance of DRP1 in glioblastoma multiforme (GBM). Methods: DRP1 expression was measured by immunohistochemistry and Western blotting. Correlations between DRP1 expression and clinicopathological parameters were determined by statistical analysis. Differences in survival were compared using the log-rank test. DRP1 expression was detected in 87.2% (41/47) of the investigated patients with GBM. Results: The patients with higher DRP1 levels had worse survival (p = 0.0398). In vitro, the silencing of DRP1 reduced cell proliferation, invasive potential, and radiation resistance. The addition of shikonin inhibited DRP1 expression and increased drug uptake. Moreover, shikonin reduced the nuclear entry of DNA repair-associated enzymes and increased radiation sensitivity, suggesting that reducing DRP1 expression could inhibit DNA repair and increase the radiation sensitivity of GBM cells. Conclusion: Our results indicate that DRP1 overexpression is a prospective radio-resistant phenotype in GBM. Therefore, DRP1 could be a potential target for improving the effectiveness of radiation therapy.

Objective: This study aims to explore in detail, the mechanism of the carbon monoxide releasing molecule-3 (CORM-3) in regulating the activity of microglia (MG) in the treatment of radiation brain injury (RBI). Methods: The brain injury models of BV2 cells and Balb/C mice were established and randomly divided into three groups: the normal control group (CON), the single radiation group (RAD), and the radiation plus CORM-3 intervention group (RAD+CORM). Immunofluorescence was used to observe the effects on activation of the MG. The expressions of inflammatory factors, such as intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS), were detected by Western blot. Neuron apoptosis and regeneration in the radiation brain injury (RBI) model were detected by neuronal nuclear antigen (NeuN)+TUNEL and NeuN+BrdU double staining. A Morris water maze was used to assess the spatial learning and memory of the mice. Results: Within 48 h after radiation, CORM-3 inhibited activation of the MG, blocked the phosphorylation of P38, and increased the expression of ICAM-1 and iNOS. Therefore, CORM-3 might alleviate MG-mediated neuronal apoptosis and promote neural regeneration in the subgranular zone (SGZ) of the dentate gyrus of the hippocampus. CORM-3 could increase the swimming distance and platform-stay time of the mice in the target platform quadrant after radiation. Conclusion: CORM-3 could effectively improve the inflammatory response induced by activation of the MG, reduce neuronal apoptosis, promote neural regeneration, and improve the learning and memory performance of mice after radiation.

Background: The Inflammatory cytokine, tumor necrosis factor-α (TNF-α), disrupts blood-brain barrier (BBB). Propofol reportedly exerts an anti-inflammatory effect in the central nervous system. Objective: We hypothesized that propofol could provide a protective effect against TNF-α-induced disruption in human cerebral microvascular endothelial cells (hCMEC/D3 cells) and explored the underlying mechanisms. Methods: The hCMEC/D3 cell monolayers were pretreated with propofol, followed by TNF-α treatment. The integrity of BBB was reflected by assessing the trans-endothelial electrical resistance (TEER) and determining the expression of proteins within tight junctions (TJs). The effect of propofol on TNF-α-modulated nitric oxide production was measured by a nitrate reductase assay kit. The expression of ZO-1, claudin-5, occludin, TNF receptor 1 (TNFR1), TNF receptor 2 (TNFR2), proviral-integration site for Moloney murine leukaemia virus (PIM)-1kinase, the phosphorylation of endothelial nitric oxide synthase at ser⁶³³ (peNOS-ser⁶³³) were detected by western blot. Results: In hCMEC/D3 cells, TNF-α treatment markedly disrupted the integrity of BBB. Further, we found TNF-α treatment could increase the expression of PIM-1, then activate the phosphorylation of eNOS and induce the release of nitric oxide (NO). More importantly, we found that TNF- α-impaired BBB integrity could be reversed by propofol. Conclusion: These results suggest that the PIM-1/eNOS/NO pathway plays a vital role, in which Propofol protects against TNF-α-induced blood-brain barrier disruption.

Objective: Application of diffusion tensor imaging (DTI) to explore the changes of FA value in patients with Parkinson's disease (PD) with mild cognitive impairment. Methods: 27 patients with PD were divided into PD with mild cognitive impairment (PD-MCI) group (n = 7) and PD group (n = 20). The original images were processed using voxel-based analysis (VBA) and tract-based spatial statistics (TBSS). Results: The average age of pd-mci group was longer than that of PD group, and the course of disease was longer than that of PD group. Compared with PD group, the voxel based analysis-fractional anisotropy (VBA-FA) values of PD-MCI group decreased in the following areas: bilateral frontal lobe, bilateral temporal lobe, bilateral parietal lobe, bilateral subthalamic nucleus, corpus callosum, and gyrus cingula. Tract-based spatial statistics-fractional anisotropy (TBSS-FA) values in PD-MCI group decreased in bilateral corticospinal tract, anterior cingulum, posterior cingulum, fornix tract, bilateral superior thalamic radiation, corpus callosum(genu, body and splenium), bilateral uncinate fasciculus, bilateral inferior longitudinal fasciculus, bilateral superior longitudinal fasciculus, bilateral superior fronto-occipital fasciculus, bilateral inferior fronto-occipital fasciculus, and bilateral parietal-occipital tracts. The mean age of onset in the PD-MCI group was greater than that in the PD group, and the disease course was longer than that in the PD group. Conclusion: DTI-based VBA and TBSS post-processing methods can detect abnormalities in multiple brain areas and white matter fiber tracts in PD-MCI patients. Impairment of multiple cerebral cortex and white matter fiber pathways may be an important causes of cognitive dysfunction in PD-MCI.

Background: There is some controversy whether stroke history is an independent risk factor for poor prognosis of stroke or not. This study aimed to investigate the difference of mortality, disability and recurrent rate of ischemic stroke patients without and with stroke history, as well as to explore the effect of stroke history on stroke prognosis. Methods: We analyzed patients with ischemic stroke enrolled in the China National Stroke Registry which was a nationwide, multicenter, and prospective registry of consecutive patients with acute cerebrovascular events from 2007 to 2008. Multivariable logistic regression was performed to assess the risk of worse prognosis of stroke history in patients with ischemic stroke. Results: A total of 8181(65.9%) patients without stroke history and 4234(34.1%) patients with stroke history were enrolled in the study. The mortality, recurrence, modified Rankin Scale (mRS) 3-6 rate was 11.4%, 14.7% and 28.5% respectively at 1 year for patients without stroke history, which was significantly lower than that of 17.3%, 23.6%, 42.1% in patients with stroke history, respectively. Multivariable analysis showed that patients with stroke history had higher risk of death [odds ratio (OR) 1.34,95% confidence interval (CI) 1.17-1.54], recurrence (OR 1.47, 95% CI 1.31-1.65) and mRS 3-6 (OR 1.49,95% CI 1.34-1.66) at 1 year. Conclusion: After adjusting for the potential confounders, stroke history was still an independent risk factor for poor prognosis of ischemic stroke, which further emphasizes the importance of secondary prevention of ischemic stroke. The specific causes of poor prognosis in patients with history of stroke need to be furtherly investigated.

Background: Stroke is a major cause of death and disability worldwide. Among its complications, post-stroke depression (PSD) leads to a significant burden. The diagnosis of PSD is complex, and there are no biomarkers that can assist in its early identification and adequate management. Objective: The aim of the present study is to investigate peripheral biomarkers in the acute phase of stroke and their potential association with depressive symptoms. Methods: We evaluated 60 patients in the acute phase of stroke by using standardized instruments of psychiatric and neurological assessment (Mini International Neuropsychiatric Interview-Plus- MINI-Plus, Hospital Anxiety and Depression Scale-HADS, and National Institutes of Health Stroke Scale-NIHSS) and measured peripheral biomarkers. Results: In multivariate analysis, low peripheral levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and higher NIHSS scores were associated with PSD. The severity of depressive symptoms was inversely correlated with sTREM-1 and glial cell-derived neurotrophic factor (GDNF) levels. Conclusion: This is the first study indicating an association between sTREM-1 and PSD. Our results may point to the involvement of glial mechanisms in the manifestation of depressive symptoms after stroke.

Objective: To analyze the incidence and risk factors of microbleeds lesions and to use thromboelastography (TEG) to evaluate the relationship between perioperative platelet function and microbleed events in patients with unruptured intracranial aneurysms (UIAs) undergoing Stent-Assisted Coil (SAC) embolization. Methods: We retrospectively enrolled 261 patients with UIAs undergoing SAC embolization between November 2017 and October 2019. All patients received unanimous antiplatelet protocol (aspirin 300 mg and clopidogrel 300 mg). Platelet function was evaluated by TEG, and magnetic resonance susceptibility-weighted imaging (SWI) was performed for microbleeds detection before and after surgery. Univariate and multivariate logistic regression analyses were used to identify potential risk factors for microbleeds following embolization. Results: Microbleed lesions were identified in 122 of 261 patients (46.7%). Most of the microbleeds were asymptomatic, except for 22 patients complaining slight headaches, and 3 patients who developed cerebral hemorrhage after discharge. Among the clinical characters, female, previous intracerebral hemorrhage (ICH) history and TEG parameters variation (higher reaction time (R) and lower maximum amplitude of adenosine diphosphate (MAADP)) were associated with microbleeds occurrence. Subsequent multivariate analysis indicated that gender, hemorrhage history, R, and MAADP were still independent risk factors of microbleeds. The R-value (>7.6 min) and MAADP (<29.2 mm) were predictive values, yielding areas under the receiver operating curve (ROC) of 0.76 (95% CI 0.70 to 0.82) and 0.89 (95% CI 0.86 to 0.93), respectively. Conclusion: The incidence of microbleeds may be high in UIA patients treated with SAC and dual antiplatelet therapy. Lesions occurred more frequently in female patients and patients with ICH history. Among the TEG parameters, the R-value and MAADP were predictors for microbleed events.