Current Neurovascular Research - Volume 19, Issue 4, 2022

Background: Secretoneurin is a neuropeptide expressed from endocrine, neuroendocrine, and neural tissues. Our study aimed to investigate whether there was a relationship between secretoneurin levels and the severity of traumatic brain injury (TBI). Methods: Ninety patients aged over 18 years who were admitted to the emergency department with head trauma between April 2020 and October 2020 and 20 healthy volunteers (control group) were included in the study. Patients were divided into three groups according to Glasgow Coma Scale scores: Mild TBI (n=33), moderate TBI (n=28), and severe TBI (n=29). The final status of the patients was evaluated in three groups: exitus, discharge with Glasgow Outcome Scale (GOS) ≤ 3 and discharge with GOS >3. Results: The median secretoneurin levels of patients with severe TBI 31.71 (14.21-70.95) were found to be significantly higher than in those with moderate TBI [17.30 (10.71-69.27) (P=0.025), and patients with moderate TBI had a substantially higher level of secretoneurin than those with mild TBI 11.70 (6-16.25) (P<0.001). There was no statistically significant difference between the median secretoneurin levels in patients with mild TBI and the control group 10.73 (5.33-13.18) (P=0.999). The secretoneurin cut-off value of >18.13 ng/mL had a sensitivity of 83.87% and a specificity of 77.97% for poor neurologic outcomes (AUC 0.86, 95% CI: 0.77- 0.92). The secretoneurin cut-off value of >20.67 ng/mL had a sensitivity of 90.91% and a specificity of 74.68% for mortality (AUC 0.85, 95% CI: 0.76-0.92). Conclusion: Secretoneurin can be a useful biomarker in diagnosing patients with moderate-tosevere TBI. It may also guide physicians in predicting the clinical outcome of patients with TBI.

Background: We investigated the association between N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) levels upon hospital admission and early hematoma growth (HG), inhospital pneumonia and major disability in patients with acute intracerebral hemorrhage (ICH). Methods: A total of 353 ICH patients from January 2014 to February 2019 were included in the present study. Patients were divided into three groups based on the admission NT-proBNP levels (T1: <61; T2: 61-199; T3: ≥199 pg/mL). Logistic regression models were used to estimate the effect of NT-proBNP on early HG, in-hospital pneumonia, and major disability upon hospital discharge (modified Rankin Scale score ≥5) in ICH patients. Results: There was no significant association observed between baseline NT-proBNP levels and early HG (P-trend =0.249). The risk of in-hospital pneumonia was significantly higher in patients with the highest NT-proBNP level (T3) (adjusted odds ratio [OR] 2.13; 95% confidence interval [CI], 1.11-4.08) and higher NT-proBNP level (T2) (adjusted OR 2.18; 95% CI, 1.19-4.00) compared to those with lowest NT-proBNP level (T1). The highest NT-proBNP level (T3) was associated with a 3.55-fold increase in the risk of major disability at hospital discharge (adjusted OR 3.55; 95% CI, 1.23-10.26; P-trend =0.013) in comparison to T1 after adjustment for potential covariates, including pneumonia. Conclusion: Increased NT-proBNP at admission was independently associated with in-hospital pneumonia and major disability upon discharge but not early hematoma growth in acute ICH patients.

Background: Cerebrovascular lesions could induce affective disorders; however, the depression- and anxiety-related symptoms caused by Chronic Cerebral Hypoperfusion (CCH) and the roles of different Hyperpolarization-activated Cyclic Nucleotide-gated (HCN), KCNQ and G protein-coupled inwardly rectifying potassium (GirK) channel subunits in these pathological processes have been poorly elucidated so far. Objective: To investigate the behavioral change and the alteration of HCN, KCNQ, and GirK subunits in amygdale rats suffering from CCH. Methods: Permanent bilateral occlusion of the common carotid arteries was used to induce CCH. Anxiety and depression levels were assessed by the elevated plus maze test, sucrose preference test and forced swimming test to classify rats as highly anxious or depressive ‘susceptibility’ vs. ‘unsusceptibility’. The expression of brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrKB), HCN1/2, KCNQ2/3, and GirK1/2/3 were quantified by Western blotting. Results: The main emotional change caused by 4 weeks of CCH is likely to be anxiety-like behavior (50%), accompanied by a down-regulation of BDNF and TrKB expression in amygdale. The increase of HCN1 and decrease of KCNQ3 expression in amygdale may be factors to blame for anxiety- like symptom caused by CCH, and the increase of KCNQ2 and Girk1 expression in amygdale may play a role in resilience to the anxiety induced by CCH. Conclusion: The different subunits of HCN, KCNQ and GirK channels in amygdale may contribute to distinct response to aversive stimuli or stress induced by CCH that evokes divergent influences on anxiety-like behavior in rats.

Background: Acupuncture has been wildly applied for cerebral ischemia treatment in China for thousands of years, while the specific mechanism remains uncertain. Recently, many studies have shown that acupuncture promotes angiogenesis after ischemia occurs. Here, we examined the effect of electro-acupuncture (EA) exosomes on angiogenesis in hypoxia-induced human umbilical vein endothelial cells (HUVECs). Objective: To investigate whether EA exosomal miR-210 promotes angiogenesis in the hypoxiainduced HUVECs via the HIF-1α/VEGF/Notch 1 signal pathway. Methods: The middle cerebral artery occlusion (MCAO) model was established and treated with EA therapy. Then, exosomes were identified and isolated from rats' plasma in the MCAO+EA group by transmission electron microscopy (TEM), surface markers expressions, and PKH26 reagent. MiR- 210 mimic, miR-210 inhibitor, and HIF-1α were transfected. Flow cytometry, CCK-8 assay, and Transwell assay were conducted to assess the migration, apoptosis, and proliferation of each group of cells. Western blot and quantitative PCR were performed to detect the CD34, HIF-1α, VEGF, Notch 1, and miR-210 expression levels in each group. Results: MiR-210 was significantly upregulated in exosomes of the MCAO plasma, and further enhanced by EA therapy. EA-EXOs and miR-210 mimic inhibited cell apoptosis, promoted cell proliferation and cell migration in hypoxia-induced HUVECs. However, the miR-210 inhibitor reversed the proliferation and migration number induced by EA-EXOs. Besides, EA-EXOs and miR- 210 mimic further enhanced those HIF-1α, VEGF, and Notch 1 levels compared to the hypoxia treatment only. Silencing HIF-1α or miR-210 reversed the high expressions of those three angiogenic factors induced by hypoxia and EA-EXO. qPCR showed similar trends with their relative mRNAs. To analyze these associations quantificationally, Spearman's rank correlation coefficient was calculated. As revealed by results, the expression of proteins and mRNA were highly correlative with each other. Conclusion: These results indicated that EA-EXO miR-210 promotes angiogenesis in hypoxia conditions via HIF-1α/VEGF/Notch 1 signal pathway.

Background and Purpose: Most studies of cerebral microbleeds place more emphasis on the elderly, which made it difficult to obtain data on youth, particularly young ischemic stroke patients. Our study sought to investigate the incidence and related risk factors of cerebral microbleeds in young ischemic stroke patients. Methods: Young ischemic stroke patients who sought medical advice at Beijing Chaoyang Hospital between June 2016 and September 2020 were included in our study. The clinical and imaging data of these patients were collected and assessed. These patients were grouped by cerebral microbleed presence, count, and location. Univariate and multivariate logistic regression analyses were performed to investigate the association between these groups and screen the influencing factors of cerebral microbleeds in young patients with ischemic stroke. Results: Among the 187 young ischemic stroke patients, the prevalence of microbleeds was 16%. The presence of cerebral microbleeds was associated with hypertension (odds ratio [OR] 8.787, 95% confidence interval [CI] 1.016-76.006, P=0.048), lower estimated glomerular filtration rate (OR 0.976, 95%CI 0.957-0.995, P=0.014) and moderate/severe white matter hyperintensity (OR 10.681, 95%CI 3.611-31.595, P<0.001) in young ischemic stroke patients. Conclusion: Cerebral microbleeds were common in young ischemic stroke patients and were associated with hypertension, lower estimated glomerular filtration rate, and moderate/severe white matter hyperintensity.

Objective: Mechanical thrombectomy (MT) is an effective treatment for large vessel occlusion (LVO) with a high successful recanalization (SR) rate. However, MT fails in a proportion of patients, leading to poor clinical outcomes. We analyzed the factors associated with the failure of MT. Methods: A total of 648 consecutive patients with MT were enrolled. MT failure was defined as 0,1, or 2a of modified Thrombolysis in Cerebral Infarction (mTICI) grade. Failed MTs were divided into 3 categories, reaching failure, passage failure, and recanalization failure (RF). Various factors in RF and SR groups were analyzed with 1: 1 propensity score matching. Results: Failed MT was observed in 97 patients (14.3%). Among them, 69 patients (10.2% of the entire cohort, 71.1% of the failed MT group) were included in the RF group. Propensity matching analysis with 69 patients in each group showed that the RF group had a higher rate of residual intracranial atherosclerotic stenosis (ICAS) than the SR group (30.4% vs. 14.5% P = 0.003). The rates of 4 or more passages and no change of method were significantly higher in the RF group than in the SR group (34.8% vs. 13.0%; P = 0.001 and 28.9% vs. 8.7%; P = 0.001). Conclusion: The failure rate for all of the MT was approximately 15%, and RF accounted for more than 70% of the failed MT. RF was associated with residual ICAS. In cases with RF, even in repeated attempts for recanalization, an alteration of the thrombectomy method should be considered.