Current Neurovascular Research - Volume 18, Issue 3, 2021

Background: Nogo-66 antagonistic peptide (NEP1-40) offers the potential to improve spinal cord injury (SCI). Objective: To explore the effect of NEP1-40 overexpression on neural stem cells (NSCs) regulating the axon regeneration of injured neurons. Methods: We isolated NSCs from brain tissues of pregnant rat fetuses and used Nestin immunofluorescence to identify them. The NEP1-40 overexpressing NSCs were constructed by transfection with the NEP1-40-overexpressing vector. The expression of NSCs differentiation associated markers, including Tuj-1, GFAP, Oligo2, and MBP, were detected by RT-PCR, western blotting, and immunofluorescence. NeuN immunofluorescence staining was used to measure the number of neurons. And western blotting was used to detect the phosphorylation levels of LIMK1/2, cofilin, and MLC-2 and the protein levels of GAP-43, MAP-2, and APP. Results: The NEP1-40 overexpression promoted the expression level of Tuj-1, Oligo2, and MBP, and increased the number of Tuj-1, Oligo2, and MBP positive cells. NEP1-40-overexpressing NSCs (NEP-NSCs) improved NeuN positive cells of co-culture with injured neurons. And NEP-NSCs also increased the protein levels of axon regeneration indicators (GAP-43, MAP-2) and decreased APP protein level. In addition, the phosphorylation level of LIMK1/2, cofilin, and MLC-2 were markedly decreased in NEP-NSCs. Conclusion: NEP1-40 overexpression enhanced the ability of NSCs differentiation into neurons and promoted axon regeneration by inhibiting the Nogo-A/NgR1 signaling pathway. This study provides an alternative gene modified transplantation NSCs for the SCI treatment.

Introduction: The Low-Profile Visualized Intraluminal Support (LVIS) devices are a new generation of self-expandable, high-porosity stents approved for the treatment of large to giant wide-necked intracranial aneurysms via stent-assisted coiling. Here we report the radiographic and clinical outcomes seen with LVIS, LVIS Jr. and LVIS Blue from a single institution over a fiveyear period. Methods: Patients with intracranial aneurysms treated by LVIS, LVIS Jr. and LVIS Blue technology over a five-year period (2012 - 2017) at our institution were retrospectively reviewed. Results: Seventy-four patients (55 females and 19 males; average age = 59.2) with 74 aneurysms underwent embolization of intracranial aneurysms using LVIS (N = 10), LVIS Jr. (N = 47) or LVIS Blue (N = 12) devices at our institution over the study period. The most common location of treated aneurysms was the anterior communicating artery (31%), followed by the basilar artery (19%), and the middle cerebral artery (13%). The mean neck and dome sizes were 3.9±1.5mm and 6.6±3.2mm, respectively. The median follow-up time was 6 months. At the last radiographic follow- up, 93.1% of patients had complete occlusion (RR-I or OKM-D). In 5 cases (7%), the LVIS stent failed to open, requiring balloon angioplasty (N = 3) or stent recapture and use of a non-LVIS branded device (N = 2). Five patients had post-embolization infarcts, and 1 patient had an intra-operative dome rupture. Conclusion: LVIS brand of stents is a safe, effective, and technically feasible treatment strategy for wide-neck intracranial aneurysms, with high deployment success and aneurysm obliteration rates.

Background: The association between atrial fibrillation (AF) and the prognosis of intravenous thrombolysis (IVT) in patients with Acute Ischemic Stroke (AIS) is debated. Hypokalemia is highly prevalent in patients with AF. We aimed to investigate the effect of hypokalemia and AF on the prognosis of AIS patients following IVT. Methods: AIS patients undergoing IVT were enrolled and divided into four groups: normokalemia and non-AF, normokalemia and AF, hypokalemia and non-AF, hypokalemia and AF. Logistic regression was applied to analyze the impact of hypokalemia, AF, and their combination on the prognosis of patients. Results: The analysis included 567 patients, 184 with 3-month poor prognosis (modified Rankin Scale score of 3-6). Following adjustment of risk factors, hypokalemia and AF increased the risks for 3-month poor prognosis (adjusted Odds Ratios (aOR) = 4.97; 95% confidence interval (CI), 1.99-12.44, P =.001), early neurological deterioration (END) (aOR=7.98; 95% CI, 3.55-17.95, P <.001), 1-year poor prognosis (aOR=5.05; 95% CI, 1.99-12.81, P =.001), 1-year all-cause death (aOR =6.95; 95% CI, 2.35-20.56, P <.001). Patients with normokalemia and AF merely increased the risk of 1-year all-cause death (aOR=2.69; 95% CI, 1.10-6.61, P=.013). Patients with hypokalemia and non-AF were not associated with any poor prognosis. There were combined and interactive effects of hypokalemia with AF on the 3-month poor prognosis (P for interaction =.039) and END (P for interaction=.005). Conclusion: Hypokalemia and AF synergistically increased the risk of near-term poor prognosis, END, long-term poor prognosis, and all-cause death of AIS patients following IVT.

Background: MiR-582-5p has been demonstrated to protect against ischemic stroke. However, its implication in the progression of neonatal hypoxic-ischemic encephalopathy (HIE) has not been explored. Methods: In this study, we used an in vitro model of oxygen-glucose deprivation (OGD) to investigate the protective effect of miR-582-5p on PC12 cells. OGD-induced inhibition of cell viability and promotion of cell death was assessed by CCK-8 assay and flow cytometry. Real-time PCR and enzyme-linked immunosorbent assay (ELISA) were utilized to examine the levels of inflammatory cytokines. The effects of miR-582-5p on OGD-induced oxidative injury were assessed by the determination of oxidative stress indicators. Furthermore, dual-luciferase reporter assay and gain-offunction assay were used to determine the mechanism of miR-582-5p in OGD-induced cell injury. Results: The expression of miR-582-5p was reduced upon OGD treatment in PC12 cells. Overexpression of miR-582-5p inhibited OGD-induced PC12 cell injury by regulating cell viability, apoptosis, inflammatory responses, and oxidative stress. MiR-582-5p targeted and negatively regulated high mobility group box 1 (HMGB1). MiR-582-5p presented protective effects on OGD-induced PC12 cell injury by targeting HMGB1. Conclusion: Our results indicated that miR-582-5p ameliorates neuronal injury by inhibiting apoptosis, inflammation, and oxidative stress through targeting HMGB1.

Objective: To determine the effect of PARP1 polymorphism on gene interactions. Methods: A total of 500 patients and 500 healthy controls were enrolled. Results: Analysis of clinical data showed that patients with stroke, diabetes, hypertension, and elevated serum triglyceride levels had higher levels of alcohol and smoking. The polymorphism of PARP1rs8679 was inversely associated with the risk of ischemic stroke. Patients with PARP1rs8679AG/ GG genotypes had a lower incidence of an initial stroke. Compared with the wild genotype, mRNA levels of PARP1 were reduced. MiR-124-5p directly induced PARP1 inhibition through the gain binding ability of 3 'UTR binding. Conclusion: Single nucleotide polymorphism (SNP) rs8679 in PARP13UTR can prevent ischemic stroke.

Objective: This study aims to investigate the correlation between cerebral blood flow (CBF) values and neonatal behavioral neurological assessment (NBNA) in hypoxic-ischemic encephalopathy (HIE), the relationship between early CBF value changes and the prognosis of neonatal HIE, and the consistency between the clinical grading and magnetic resonance (MR) grading of HIE. Methods: Forty neonates with HIE were scanned using the three-dimensional arterial spin labeling (ASL) sequencing of the cranial Magnetic Resonance Imaging (MRI). These newborns were classified as having mild, moderate and severe HIE, according to the clinical grading, and as being normal or having mild, moderate, or severe HIE, according to the MRI grading. Then, the consistency of these two grading systems was compared. Afterwards, the differences in the CBF values of neonates in groups with mild, moderate and severe HIE were compared. In addition, these neonates were grouped according to their NBNA scores. A score of ≥35 was considered a good prognosis, while a score of ≤35 was considered a poor prognosis. The differences in CBF values between these two groups were compared, and the correlation between the CBF values and NBNA scores was determined. Results: There was a strong consistency between the evaluation results for the clinical grading and MR grading (kappa value = 0.672, P<0.001). The differences in CBF values for the basal ganglia (BG) area and thalamus, and the differences in NBNA scores for groups with mild, moderate, or severe HIE were statistically significant (P<0.05). The differences between the poor prognosis group and the good prognosis group, in terms of the CBF values for the BG area and thalamus, and the NBNA scores were statistically significant (P<0.05). The CBF values in the BG region and thalamus were closely and negatively correlated with the NBNA scores. Conclusion: Early CBF values in the BG area and thalamus can objectively and visually reflect the severity of the HIE, and be used to predict the outcome of functional brain damage, allowing early neuroprotective treatment to be initiated. The higher the perfusion in the BG region and thalamus, the lower the NBNA score, and the worse the prognosis would likely be. ASL combined with the NBNA score provides a more comprehensive classification for HIE and a more accurate assessment of the clinical prognosis, providing more medical imaging information for early clinical treatment.

Objective: The present study aimed to observe the therapeutic effect of elastic bandages on improving knee hyperextension in patients with stroke after correcting the foot varus. Methods: A total of 45 patients with stroke admitted to the hospital from January to August 2019 were enrolled in the present prospective study. Elastic bandages were used to fix the affected foot in a mild valgus position. Before and after the intervention, the Noitom walking function evaluation system was adopted, and the Timed Up and Go (TUG) test and the 10-meter walking test were conducted. The gait speed, stride length, knee angle, and the number of knee hyperextensions >5° were selected as the results. The weight-bearing time of the affected leg was evaluated, and the changes in the control ability of the affected limb before and after the intervention were compared. Results: It was found that compared with before treatment, the time of knee hyperextension was significantly reduced after fixation with the elastic bandage, and the knee extension angle was significantly reduced (p < 0.05). After the treatment, the gait speed was significantly higher than before the treatment (p < 0.05), but there was no statistically significant difference in the stride length (p > 0.05). After the treatment, the time in the TUG test was significantly shorter than before the treatment (p < 0.05), together with an obvious increase in the weight-bearing time of the affected leg (p < 0.05). Conclusion: Correcting foot varus could improve the biomechanics of the lower limbs and improve the symptoms of knee hyperextension in patients with stroke, thereby improving the control ability of the affected limb and improving the walking function.

Objective: To explore the efficacy of functional electrical stimulation (FES)-assisted rehabilitation cycling on the functional recovery of lower limbs in patients with hemiplegic stroke and the assessment value of surface electromyography (sEMG). Methods: A total of 66 patients with stroke accompanied by hemiplegia of the lower limbs were enrolled in the present prospective study and randomly divided into the experimental group and control group, with 33 patients in each group. FES-assisted rehabilitation cycling was applied in the experimental group, while only rehabilitation cycling was performed without setting the stimulation parameters in the control group. sEMG and the Fugl-Meyer assessment (FMA) were carried out, and the modified Barthel index (MBI) of the lower limbs was assessed before treatment and after 4 weeks and 8 weeks of treatment. Results: There were no significant differences in the evaluation results of sEMG, FMA, and MBI of the lower limbs between the two groups of patients before the treatment (p > 0.05). After 4 weeks of treatment, compared with the control group, there were significant differences in the results of sEMG, FMA, and MBI of the lower limbs in the experimental group (p < 0.05). In the experimental group, the difference in sEMG was statistically significant (p < 0.05). After 8 weeks of treatment, compared with the control group, there were significant differences in the results of sEMG, FMA, and MBI of the lower limbs in the experimental group (p < 0.05). In the experimental group, the differences in the results of sEMG, FMA, and MBI of the lower limbs were statistically significant (p < 0.05). The inter-group comparison of the results of sEMG, FMA and MBI of the lower limbs was statistically significant (p < 0.05) in the control group. Conclusion: FES-assisted rehabilitation cycling might promote the recovery of the motor function of the lower limbs in patients with stroke and improve the sEMG signal of the lower limbs.

Background: Cardiometabolic Index (CMI) was associated with several risk factors for stroke; however, few studies assessed the role of CMI in stroke risk. Objective: This study aimed to assess the association between CMI and stroke in a population- based cross-sectional study. Methods: This study included 4445 general residents aged ≥40 years selected by multistage stratified random cluster sampling. CMI was calculated as the product of the ratio of waist circumference to height (WHtR) and the ratio of triglyceride levels to high-density lipoprotein cholesterol levels (TG/HDL-C). Participants were categorized according to CMI quartiles: quartile 1 (Q1), quartile 2 (Q2), quartile 3 (Q3), and quartile 4 (Q4). Multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used to assess the association between CMI and stroke. Results: A total of 4052 participants were included in the study, with an overall stroke prevalence of 7.2%. The prevalence of stroke increased with CMI quartiles, ranging from 4.4% to 9.2% (p for trend <0.001). Compared with Q1, stroke risk for Q2, Q3, and Q4 were 1.550-, 1.693-, and 1.704- fold, respectively. The area under the ROC curve (AUC) (95% CI) was 0.574 (0.558-0.589) for CMI, 0.627 (0.612-0.642) for WHtR, 0.556 (0.540-0.571) for TG/HDL-C. CMI was inferior to WHtR (p=0.0024), but CMI had a marginal advantage over TG/HDL-C (p<0.0001) in terms of its stroke discrimination ability. Conclusion: Although there was a strong and independent association between CMI and stroke in the general population, CMI had limited discriminating ability for stroke. Thus, new parameters should be developed.

Background: The relationship between serum lipids and migraine remains controversial. Objective: This study aimed to analyze the association between serum lipids and severe headache or migraine in the general population. Methods: Data were collected from a nationally representative sample of participants in the National Health and Nutrition Examination Survey from 1999 to 2004. Interviewers recorded self-reported severe headaches or migraines and whether pain lasted for more than 24 h in three months. A weighted general linear model was used to estimate the association between serum lipids and severe headache or migraine. Regression analyses were performed after adjusting for age, sex, race, energy intake, sodium intake, etc. Subgroup analyses were performed using the same regression model. Results: We included 5,937 individuals in the study, with a weighted mean age of 45.8 years. Males accounted for 47.6% of the participants. After adjusting for covariates, a non-significant association was found between migraine and total cholesterol (odds ratio=0.96, 95% confidence interval= 0.85, 1.05; P=0.32), low-density lipoprotein cholesterol (odds ratio=0.96; 95% confidence interval= 0.75, 1.17, P=0.55), and high-density lipoprotein cholesterol (odds ratio=0.99; 95% confidence interval=0.49, 1.59, P=0.58) in the continuous form. In subgroup analyses, no significant association was found between total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and self-reported severe headache or migraine. Conclusion: Total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were not significantly associated with severe headache or migraine in the general American population after adjusting for covariates. The supporting information for measuring common serum lipids in general headaches and migraines is insufficient.

Background: Chronic cerebral hypoperfusion (CCH) is a contributing factor for neurodegenerative diseases. As a recently identified heptapeptide of the brain renin-angiotensin system, angiotensin-(1-7) has been revealed to activate its receptor MAS1 and thus ameliorated cognitive impairments in rats with CCH. Since hippocampal synaptic degeneration represents an important pathological basis of cognitive deficits, we hypothesize that activating MAS1-mediated signaling may alleviate CCH-induced synaptic degeneration in the hippocampus. Methods: In this study, we tested this hypothesis and uncovered the underlying mechanisms in a rat model of CCH induced by bilateral common carotid artery ligation surgery. At one week after the surgery, rats received a daily intraperitoneal vehicle injection or a non-peptidic MAS1 agonist AVE0991 for 8 weeks. During this procedure, Cerebral Blood Flow (CBF) was recorded. The levels of MAS1, amyloid-β (Aβ), neuroinflammatory cytokines, glial cell markers, and synaptophysin in the hippocampus were assessed at the end of the treatment period. Results: We showed that AVE0991 significantly alleviated hippocampal synaptic degeneration in rats with CCH. This protection might be achieved by facilitating CBF recovery, reducing hippocampal Aβ levels, and suppressing neuroinflammatory responses. Conclusion: These findings indicate that MAS1-mediated signaling may represent a novel therapeutic target for CCH-related neurodegenerative diseases.

Background: Intracerebral hemorrhage (ICH) is a major cause of death and disability globally. As a type of secondary injury after ICH, treatment for cell death can promote the recovery of neurological function. Methods: Among all the cell death, neuronal necroptosis has recently been demonstrated of significance in the pathogenesis of ICH. However, the administration of drugs against necroptosis has many limitations. Results: In the present study, we found that metformin, a first-line medication for the treatment of type 2 diabetes, can effectively inhibit neuronal necroptosis after ICH by activating the AMPK related pathway, thereby significantly improving neurological function scores and reducing brain edema. Conclusion: These results will provide a new perspective for future research in necroptosis.

Background: Coronavirus disease-19 (COVID-19) is an infectious disease with high morbidity and mortality rates. Indonesia had reported a 2.8% of mortality rate up to June 2021. Case Presentation: A strategy to control the virus spreading is by vaccination. The Indonesian Food and Drug Monitoring Agency had approved the use of CoronaVac, an inactivated virus vaccine developed by Sinovac. Most Adverse Events Following Immunization (AEFI) for Corona- Vac are mild, and the most common symptoms are injection-site pain, headache, and fatigue. Neurovascular adverse events, including thrombosis or ischaemic stroke after receiving CoronaVac have not previously been reported. Conclusion: Correspondingly, we reported three patients with an Acute Ischaemic Stroke (AIS) after the administration of CoronaVac in our hospital.

Abstract: The correlation of neuroinflammation with the development of cerebral vasospasm following subarachnoid hemorrhage has been well documented in the literature; both clinical and preclinical. The exact mechanisms by which this process occurs, however, are poorly elucidated. Recent evidence indicates that interleukin-6 is not only an important prognostic biomarker for subarachnoid hemorrhage and subsequent vasospasm development but also an integral component in the progression of injury following initial insult. In this review, we briefly highlight other pathways under investigation and focus heavily on what has been discovered regarding the role of interleukin 6 and cerebral vasospasm following subarachnoid hemorrhage. A proposed mechanistic pathway is highlighted in written and graphical format. A discussion regarding the human correlative findings and initial pre-clinical mechanistic studies is addressed. Finally, in the future investigation section, innovative developments and a clear description of areas warranting further scientific inquiry are emphasized. This review will catalyze continued discovery in this area of emerging significance and aid in the quest for effective vasospasm treatment where limited clinical therapeutics currently exist.