Current neurovascular research最新文献

Introduction: Depression is a class of important mental illness, which has become a severe health problem perplexing the world due to its high morbidity rate, high disability rate, and great disease burden. This study aimed to evaluate the role and possible mechanisms of P2RY12 in the depression-like behaviors model.

Methods: Serum samples of patients with depression-like behaviors were used to analyze the expression of P2RY12. Models of mice were given LPS via intraperitoneal injection for 7 days. Behavioral tests were executed in this experiment.

Results: The expression of P2RY12 in models of depression-like behaviors or mice with depression- like behaviors were induced. The inhibition of P2RY12 presents depression-like behaviors and reduces inflammation in the model of depression-like behaviors. P2RY12 induced NLRP3 expression and suppressed NLRP3 ubiquitination in a model of depression-like behavior. The inhibition of NLRP3 reduced the effects of P2RY12 in mice model of depression-like behaviors. The regulation of NLRP3 controlled the effects of the P2RY12 in vitro model of depression-like behaviors.

Conclusion: We conclude that P2RY12 increased neuroinflammation to accelerate depression-like behaviors by NLPR3 inflammasome, providing novel information for the treatment of depressionlike behaviors.

Background: Early neurological deterioration (END) often occurs during hospitalization in single small subcortical infarct (SSSI). While, symptoms on admission were rarely reported about its performance on predicting the risk of END.

Objectives: The objective of this study is to explore the relationship between symptoms on admission and END in SSSI.

Methods: Patients with SSSI in the lenticulostriate artery (LSA) territory presenting within 72 hours of stroke onset were screened prospectively. Clinical characteristics, including symptoms on admission, laboratory tests and imaging findings, were collected. Based on the body regions involved including spherical face (SF), upper limb (UL) or lower limb (LL), symptoms on admission were classified into single spherical face (sSF) and any involvement of limbs (AL). END was defined as ≥2 points increase in total National Institutes of Health Stroke Scale (NIHSS) score or ≥ 1 point increase in motor score within 72 hours after admission. Multivariate logistic regression was used to analyze factors associated with END.

Results: Out of 5,832 ischemic stroke patients in the database, 394 patients were finally enrolled in analysis. 65 patients (16.5%) developed END. Multivariable logistic regression revealed that symptoms with LL (OR 2.337, 95% CI 1.041-5.246), UL (OR 2.936, 95% CI 1.349-6.390) were both associated with END, while the involvement of SF (OR 0.447, 95% CI 0.249-0.804) showed the opposite result. Further analysis found that symptoms with AL (OR 3.958, 95% CI 1.355-11.565) showed a higher risk of END compared to sSF after adjustment.

Conclusion: Our results discovered that symptoms with AL carried a higher risk of END than those involving sSF in SSSI.

Background: Receptor-interacting serine-threonine protein kinase 3 (RIP3) was previously discovered to be an important medium in the occurrence and development of major atherosclerotic cerebral infarction. However, the role of RIP3 in acute ischemic stroke remains unclear.

Objective: This study aimed to explore the correlation between plasma levels of RIP3 and acute ischemic stroke with large-artery atherosclerosis (LAA).

Methods: This prospective study enrolled 116 patients with LAA, 40 healthy controls, and 30 acute ischemic stroke patients with small-artery occlusion. The patients with LAA were divided according to the quartile of plasma levels of RIP3. A logistic regression model was used for comparison. The ROC curve was performed to evaluate the predictive value.

Results: In patients with LAA, the RIP3 levels in patients with poor outcomes as well as neurological deterioration were significantly higher than those with good outcomes (P < 0.001) and without neurological deterioration (P = 0.014). Patients in the highest levels of plasma RIP3 quartile were more likely to have neurological deterioration (OR, 11.07; 95% CI, 1.990-61.582) and poor outcomes (OR, 35.970; 95% CI, 5.392-239.980) compared with the lowest. The optimal cut-off value for neurological deterioration was 1127.75 pg/mL (specificity, 66.7%; sensitivity, 69.2%) and that for poor prognosis was 1181.82 pg/mL (specificity, 89.7%; sensitivity, 62.1%).

Conclusion: Elevated levels of plasma RIP3 were significantly associated with neurological deterioration and poor prognosis in patients with LAA. A significant increase in plasma RIP3 levels can predict neurological deterioration and the poor prognosis of these patients.

Objective: This study aimed to investigate changes in the levels of serum lactate dehydrogenase (LDH), hypersensitive C-reactive protein (hs-CRP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) in pediatric patients with traumatic brain injury and the clinical significance of detecting these changes for the evaluation of injury severity and patient progress.

Methods: A retrospective study was conducted on 40 pediatric patients admitted to the Tongren Hospital of China Capital Medical University with traumatic brain injury between January 2018 and December 2019. Immunoturbidimetric assay and electrochemiluminescence were used to detect the serum levels of LDH, hs-CRP, and NT-proBNP. Correlation analysis was used to determine the degree of association between the indicators and the sensitivity and specificity of each indicator.

Results: The serum levels of LDH, hs-CRP, and NT-proBNP in the poor-prognosis group were higher than those in the good-prognosis group, and the differences were statistically significant (P < 0.05).

Conclusion: The detection of serum LDH, hs-CRP, and NT-proBNP might be of great significance for the evaluation of the severity of a traumatic brain injury, disease progression, and the prognosis of pediatric patients with traumatic brain injury. The combined detection of the relevant indicators could provide more effective sensitivity and specificity and therefore offer better guidance and assistance in clinical practice.

Background: Alzheimer's Disease (AD) impairs memory and cognitive functions in the geriatric population and is characterized by intracellular deposition of neurofibrillary tangles, extracellular deposition of amyloid plaques, and neuronal degeneration. Literature suggests that latent viral infections in the brain act as prions and promote neurodegeneration. Memantine possesses both anti-viral and N-methyl-D-aspartate (NMDA) receptor antagonistic activity.

Objectives: This research was designed to evaluate the efficacy of antiviral agents, especially valacyclovir, a prodrug of acyclovir in ameliorating the pathology of AD based on the presumption that anti-viral agents targeting the Herpes Simplex Virus (HSV) can have a protective effect on neurodegenerative diseases like Alzheimer's disease.

Methods: Thus, we evaluated acyclovir's potential activity by in-silico computational docking studies against acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase 1 (BACE-1). These findings were further evaluated by in-vivo scopolamine-induced cognitive impairment in rats. Two doses of valacyclovir, a prodrug of acyclovir (100 mg/kg and 150 mg/kg orally) were tested.

Results: Genetic Optimisation for Ligand Docking scores and fitness scores of acyclovir were comparable to donepezil. Valacyclovir improved neurobehavioral markers. It inhibited AChE and BuChE (p<0.001) enzymes. It also possessed disease-modifying efficacy as it decreased the levels of BACE-1 (p<0.001), amyloid beta 1-42 (p<0.001), amyloid beta 1-40 (p<0.001), phosphorylatedtau (p<0.001), neprilysin (p<0.01), and insulin-degrading enzyme. It ameliorated neuroinflammation through decreased levels of tumour necrosis factor α (p<0.001), nuclear factor-kappa B (p<0.001), interleukin 6 (p<0.001), interleukin 1 beta (p<0.001), and interferon-gamma (p<0.001). It also maintained synaptic plasticity and consolidated memory. Histopathology showed that valacyclovir could restore cellular density and also preserve the dentate gyrus.

Conclusion: Valacyclovir showed comparable activity to donepezil and thus can be further researched for the treatment of Alzheimer's disease.

Objective: In this study, we investigated the relationship between serum ischemic modified albumin (IMA) levels and other hematologic features and middle cerebral artery (MCA) severe stenosis/occlusion in acute ischemic stroke (AIS) patients.

Methods: The levels of serum IMA and Albumin (ALB) of 169 AIS patients were measured, and the ratio of IMA to albumin (IMAR) and the albumin-adjusted ischemia-modified albumin index (IMA index) were calculated. Different combinations of other hematologic changes and clinical features of the patients were analyzed.

Results: The results indicated that the levels of blood IMA and IMAR were significantly higher in the group with severe intracranial stenosis/occlusion than in the group with non-severe stenosis/ occlusion in AIS patients, while the CHE levels were significantly lower than those in the other groups. In the MCA severe stenosis/occlusion group, the levels of blood IMA and IMAR were significantly higher than that in the other vascular severe stenosis/occlusion groups, while the IMA index, ALB, and CHE were significantly lower than that in the other groups. Multiple linear regression analysis showed a significant negative correlation between IMA and albumin. A combined diagnostic ROC curve analysis showed that among AIS patients, the best combination for determining severe stenosis/occlusion of the great intracranial arteries was the admission NIHSS score + CHE (AUC = 0.783). The best combination for determining severe stenosis or occlusion of the MCA in AIS patients was IMAR combined with the admission NIHSS score and CHE (AUC = 0.827).

Conclusion: The combined use of IMA, IMAR, and the IMA index has some diagnostic value in AIS caused by severe stenosis or occlusion of the MCA. IMAR, CHE, and the admission NIHSS scores are the best combinations to determine whether an AIS patient has severe stenosis or occlusion of the MCA.

Background: Discussing the quality measurements based on interrupted time series in ischemic stroke, delays are often attributed to weekends effect. This study compared the metrics and outcomes of emergent endovascular thrombectomy (EST) during working hours versus non-working hours in the emergency department of an Asian medical center.

Methods: A total of 297 patients who underwent EST between January 2015 and December 2018 were retrospectively included, with 52.5% of patients presenting during working hours and 47.5% presenting during nights, weekends, or holidays.

Results: Patients with diabetes were more in non-working hours than in working hours (53.9% vs. 41.0%; p=0.026). It took longer during nonworking hours than working hours in door-to -image times (13 min vs. 12 min; p=0.04) and door-to-groin puncture times (median: 112 min vs. 104 min; p=0.042). Significant statistical differences were not observed between the two groups in neurological outcomes, including successful reperfusion and complications such as intracranial hemorrhage and mortality. However, the change in National Institute of Health Stroke Scale (NIHSS) scores in 24 hours was better in the working-hour group than in the nonworking-hour group (4 vs. 2; p=0.058).

Conclusion: This study revealed that nonworking-hour effects truly exist in patients who received EST. Although delays in door-to-groin puncture times were noticed during nonworking hours, significant differences in neurological functions and mortality were not observed between working and non-working hours. Nevertheless, methods to improve the process during non-working hours should be explored in the future.

Background: Coronary artery stenosis (CAS) ≥50% often coexists in patients with ischemic stroke, which leads to a significant increase in the occurrence of major vascular events after stroke. This study aimed to develop a nomogram for diagnosing the presence of ≥50% asymptomatic CAS in patients with ischemic stroke.

Methods: A primary cohort was established that included 275 non-cardioembolic ischemic stroke patients who were admitted from January 2011 to April 2013 to a teaching hospital in southern China. The preoperative data were used to construct two models by the best subset regression and the forward stepwise regression methods, and a nomogram between these models was established. The assessment of the nomogram was carried out by discrimination and calibration in an internal cohort.

Results: Out of the two models, model 1 contained eight clinical-related variables and exhibited the lowest Akaike Information Criterion value (322.26) and highest concordance index 0.716 (95% CI, 0.654-0.778). The nomogram showed good calibration and significant clinical benefit according to calibration curves and the decision curve analysis.

Conclusion: The nomogram, composed of age, sex, NIHSS score on admission, hypertension history, fast glucose level, HDL cholesterol level, LDL cholesterol level, and presence of ≥50% cervicocephalic artery stenosis, can be used for prediction of ≥50% asymptomatic coronary artery disease (CAD). Further studies are needed to validate the effectiveness of this nomogram in other populations.

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: Single Small Subcortical Infarction (SSSI) is an isolated small infarction in the territory of perforating artery with a maximum diameter of 20 mm in axial Diffusion-Weighted Imaging (DWI). About 20 to 30% of SSSI patients were reported to have Early Neurological Deterioration (END) in the acute phase, which brought adverse effects on long-term outcomes. The effect of the alteplase on the outcome of SSSI, especially END and long-term outcomes, was ambiguous.

Objective: The study aims to find out the efficacy and safety of intravenous recombinant tissue Plasminogen Activator (rt-PA) on long-term and short- outcomes of patients with SSSI as compared to patients who received standard medical care.

Methods: The patients were retrospectively screened from a stroke registry of the neurology department of 1st Affiliated Hospital of Zhengzhou University from January 2013 to December 2020. Based on treatment modality, patients were dichotomized into alteplase and standard medical care groups. To minimize confounding factors in subgroups, a propensity score matching analysis was done. The primary outcome was the favorable functional outcome 3 months after stroke onset, defined by attaining a score of ≤2 points on the modified Rankin scale (mRS), secondary outcome was the prevention of occurrence of END, defined as an increase of ≥2 points in the total score or ≥1point on motor subunit in the National Institutes of Health Stroke Scale (NIHSS) score within 72 hours after admission, safety features were symptomatic intracranial hemorrhage (sICH) or death. Multivariate analysis was employed to find the efficacy and safety of alteplase in the treatment of SSSI.

Results: A total of 717 patients with anterior circulation SSSI were selected, and 132 were included in the final analysis. Forty-five patients were treated with alteplase within 4.5 hours and 87 with standard medical care, and 44 pairs were successfully matched by propensity score. Pre-match data showed that the alteplase thrombolysis group showed a higher proportion of favorable outcomes at 3-month follow-up [OR=0.315, 95%CI:0.106, 0.931, P = 0.037] but did not reduce the incidence of END compared with the non-thrombolytic group [OR = 1.033, 95%CI:0.417,2.554, P = 0.943]. Post-match data showed that the alteplase group also showed a higher proportion of favorable outcomes at 3-month follow-up [OR = 0.247, 95%CI: 0.074, 0.830, P = 0.024]; however, it did not reduce the incidence of END compared with the non-thrombolytic group [OR = 1.241, 95%CI: 0.433,3.554, P = 0.688]. There was one case of asymptomatic ICH in alteplase treated patients.

Conclusion: Patients with SSSI in the anterior circulation are more likely to achieve 3 months favorable outcomes than those who were treated with standard medical care; however, treatment with alteplase may not prevent the occurrence of END.