Current neurovascular research最新文献

Background: Stroke-Induced Immunodepression (SIID) is characterized by apoptosis in blood immune populations, such as T cells, B cells, NK cells, and monocytes, leading to the clinical presentation of lymphopenia. Disulfidptosis is a novel form of programmed cell death characterized by accumulating disulfide bonds in the cytoplasm, resulting in cellular dysfunction and eventual cell death.

Objective: In this study, we investigated the association between disulfidptosis and stroke by analyzing gene sequencing data from peripheral blood samples of stroke patients.

Methods: Differential gene expression analysis identified a set of disulfidptosis-related genes (DRGs) significantly associated with stroke. Initial exploration identified 32 DRGs and their interactions. Our study encompassed several analyses to understand the molecular mechanisms of DRGs in stroke. Weighted Gene Co-Expression Network Analysis (WGCNA) uncovered modules of co-expressed genes in stroke samples, and differentially expressed gene (DEG) analysis highlighted 1643 key genes.

Results: These analyses converged on four hub genes of DRGs (SLC2A3, SLC2A14, SLC7A11, NCKAP1) associated with stroke. Immune cell composition analysis indicated positive correlations between hub genes and macrophages M1, M2, and neutrophils and negative associations with CD4+ and CD8+ T cells, B cells, and NK cells. Sub-cluster analysis revealed two distinct clusters with different immune cell expression profiles. Gene Set Enrichment Analysis (GSEA) demonstrated enrichment of apoptosis-related pathways, neurotrophin signaling, and actin cytoskeleton regulation. Associations between hub genes and apoptosis, necroptosis, ferroptosis, and cuproptosis, were also identified.

Conclusion: These results suggest that the DRG hub genes are interconnected with various cell death pathways and immune processes, potentially contributing to stroke pathological development.

Background: Migraine is implicated in oxidative stress. The oxidative balance score (OBS) assesses the combined impact of diet and lifestyle on oxidative and antioxidant balance in diseases. However, the association between OBS and migraine remains underexplored.

Objective: We aimed to examine the relationship between OBS and severe headaches or migraines among American adults.

Methods: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, defining severe headaches or migraine via self-reports and calculating OBS from 16 diaries and 4 lifestyle factors. Multivariable weighted logistic regression models were used to explore the OBS-migraine relationship, with stratified analysis for result validation.

Results: The study included 6,653 participants (average age 45.6, 52.1% male), and 19.1% reported severe headaches or migraines. There was a significant inverse association between OBS and severe headache or migraine, with an adjusted odds ratio (OR) of 0.97 (95% [confidence interval] CI: 0.96, 0.98, p < 0.001). The highest OBS tertile had an adjusted OR of 0.58 (95% CI: 0.47, 0.73) compared to the lowest. This pattern was consistent across sexes, with an adjusted OR of 0.98 (0.95, 1.00) in males and 0.97 (0.95, 1.00) in females. The adjusted OR for migraine was 0.61 (0.44, 0.87) and 0.54 (0.37, 0.79) in the highest tertile for males and females, respectively.

Conclusion: The study highlights a significant association between OBS and severe headaches or migraines, suggesting the potential role of oxidative stress in these conditions. The findings emphasize the importance of a balanced, antioxidant-rich diet and lifestyle in managing severe headaches or migraine.

Background and purpose: Immune and inflammatory response plays a central role in the clinical outcomes of stroke. This study is aimed to explore the clinical significance of the new inflammation index named pan-immune-inflammation value (PIV) in patients with acute ischemic stroke (AIS) after intravenous thrombolysis therapy (IVT).

Methods: Data were collected from 717 patients who received IVT at the First Affiliated Hospital of Soochow University. Baseline data were collected before intravenous thrombolysis. Multivariate logistic regression analysis was used to assess the association between PIV and 3 months clinical outcome after intravenous thrombolysis. We also used receiver operating characteristic (ROC) curves analysis to assess the discriminative ability of PIV, platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), and systemic immune-inflammation index (SII) in predicting 3 months poor outcome.

Results: Of 717 patients, 182 (25.4%) patients had poor outcomes at 3 months. Patients with 3 months of poor outcome had significantly higher PIV levels compared to those with favorable outcomes [316.32 (187.42-585.67) vs. 223.80 (131.76-394.97), p < 0.001)]. After adjusting for potential confounders, the risk of 3 months of poor outcome was significantly higher among patients whose PIV fell in the third quartile (244.21-434.49) and the fourth quartile (> 434.49) than those in the first quartile (< 139.93) (OR = 1.905, 95% CI: 1.040-3.489; OR = 2.229, 95%CI: 1.229-4.044). The area under the ROC curve of PIV to predict 3 months of poor outcome was 0.607 (95%CI: 0.560-0.654; p < 0.001). The optimal cut-off values of PIV were 283.84 (59% sensitivity and 62% specificity).

Conclusion: The higher levels of PIV were independently associated with 3 months of poor outcomes in AIS patients receiving IVT. PIV like other inflammatory factors (PLR, NLR, and SII), can also predict adverse outcomes after IVT in AIS patients.

The ability and facility of magnesium (Mg2+) and zinc (Zn2+) to interact with phosphate ions confer them the characteristics of essential trace elements. Trace elements are extremely necessary for the basic nucleic acid chemistry of cells of all known living organisms. More than 300 enzymes require zinc and magnesium ions for their catalytic actions, including all the enzymes involved in the synthesis of ATP. In addition, enzymes such as isomerases, oxidoreductases, lyases, transferases, ligases and hydrolases that use other nucleotides to synthesize DNA and RNA require magnesium and zinc. These nucleotides may trigger oxidative damage or important changes against free radicals. In the same way, nucleotides may play an important role in the pathophysiology of degenerative diseases, including in some clinical disorders, where vascular risk factors, oxidative stress and inflammation work to destabilize the patients` homeostatic equilibrium. Indeed, reduced levels of zinc and magnesium may lead to inadequate amount of antioxidant enzymes, and thus, acts as an important contributing factor for the induction of oxidative stress leading to cellular or tissue dysfunction. Hence, the development of zinc or magnesium enzyme inhibitors could be a novel opportunity for the treatment of some human disorders. Therefore, the objective of the present work was to assess the clinical benefits of zinc and magnesium in human health and their effects in some clinical disorders.

Background: Smad ubiquitination regulatory factor 2 (Smurf2) has been observed to alleviate ischemia-reperfusion injury. This study sought to explore the molecular mechanism of Smurf2-mediated forkhead box O4 (FOXO4) ubiquitination in oxygen-glucose deprivation/ reperfusion (OGD/R)-induced pyroptosis of cortical neurons.

Methods: Human cortical neurons (HCN-2) were subjected to OGD/R to establish a cell model of cerebral stroke. Smurf2, FOXO4, and doublecortin domain containing 2 (DCDC2) expressions were determined by RT-qPCR and Western blot. LDH release, pyroptosis-related proteins NLRP3, GSDMD-N, and cleaved-caspase-3, as well as inflammatory factors IL-1β and IL-18, were assessed by LDH assay kit, Western blot, and ELISA. The ubiquitination level of FOXO4 was determined by ubiquitination assay. The bindings of Smurf2 to FOXO4 and FOXO4 to DCDC2 were testified by Co-IP, ChIP, and dual-luciferase assays. Rescue experiments were designed to validate the role of FOXO4/DCDC2 in the pyroptosis of HCN-2 cells.

Results: Smurf2 was weakly expressed, while FOXO4 and DCDC2 were prominently expressed in OGD/R-treated HCN-2 cells. Smurf2 overexpression promoted LDH release, reduced NLRP3, GSDMD-N, and cleaved-caspase-3 proteins, and decreased IL-1β and IL-18 concentrations. Sumrf2 improved the ubiquitination level of FOXO4 to downregulate its protein level. FOXO4 is bound to the DCDC2 promoter to facilitate its transcription. Overexpression of FOXO4 or DCDC2 reversed the inhibition of Smurf2 overexpression on pyroptosis of OGD/Rtreated HCN-2 cells.

Conclusion: Smurf2 overexpression facilitated the ubiquitination of FOXO4 to reduce its protein level, thereby suppressing DCDC2 transcription and restricting OGD/R-induced pyroptosis of cortical neurons.

Background and purpose: The role of intravenous thrombolysis in patients with acute mild ischemic stroke remains highly controversial. Therefore, this study aims to analyze the efficacy and safety of intravenous thrombolysis in patients with mild ischemic stroke based on admission National Institutes of Health Stroke Scale (NIHSS) score.

Methods: The present study enrolled 507 patients with acute mild ischemic stroke admitted within 4.5 hours of symptom onset with an admission NIHSS score of 0 to 5. Patients were assigned to two groups based on admission NIHSS scores of 0 to 2 and 3 to 5, and subsequent analyses compared functional outcomes between thrombotic and non-thrombotic patients within these groups. The primary outcome was a modified Rankin score (mRS) of 0 or 1 at 90 days, representing functional independence. The safety outcomes were symptomatic intracranial hemorrhage (sICH), early neurological deterioration (END), and the rate of stroke recurrence within 90 days.

Results: Among the 267 patients with NIHSS scores of 0 to 2, 112 (41.9%) patients received intravenous thrombolysis. Overall, thrombolysis administration did not significantly improve the patient's functional prognoses at 90 days (adjusted OR=1.046, 95%CI=0.587-1.863, p = 0.878). However, there was a marked increase in the risk of sICH (p = 0.030). Of the 240 patients with NIHSS scores of 3 to 5, 155 (64.6%) patients received intravenous thrombolysis, resulting in a significant improvement in 90-day functional prognosis (adjusted OR=3.284, 95%CI=1.876- 5.749, p < 0.001) compared to those that did not receive thrombolysis intervention. Importantly, there was no significant increase in sICH incidence (adjusted OR=2.770, 95%CI=0.313-24.51, p = 0.360). There were no statistically significant differences in END or the rate of stroke recurrence within 90 days between thrombotic and non-thrombotic groups.

Conclusions: Intravenous thrombolysis is safe and effective in patients with baseline NIHSS scores of 3 to 5. In contrast, it did not improve 90-day functional outcomes in patients with NIHSS scores of 0 to 2 and instead increased the risk of sICH.

Background: The AKT/mTOR/p70S6K pathway has been shown to potentially promote spinal cord injury (SCI) repair in rats. However, its exact mechanism and beyond needs to be further explored.

Objective: This study aims to explore the AKT/mTOR/p70S6K pathway in oligodendrocyte precursor cell (OPC) differentiation, microglial polarization differentiation, and the role of these in myelin regeneration in vitro.

Methods: The isolation, induction and characterization of rat primary neuronal stem cells, OPCs and oligodendrocytes were investigated with immunofluorescence and RT-qPCR. Then, the role of AKT/mTOR/p70S6K signaling was explored using western blotting and immunofluorescence, the effect on myelination was examined with OPC-dorsal root ganglion (DRG) neurons co-culture, and the influence of M1/M2 polarization status of microglia on myelin formation was also observed by adding M1/M2 supernatants into OPC-DRG neurons co-culture.

Results: Activation of the AKT/mTOR/p70S6K pathway elevated the expression of oligodendrocyte differentiation markers, including MBP, PLP and MOG, which also promoted the colocalization of MBP and NFH in OPC-DRG neurons co-culture. More interestingly, stimulation of the AKT/mTOR/p70S6K pathway facilitated M2 polarization of rat microglia. M2 polarization of microglia enhanced OPC differentiation to oligodendrocytes and myelin formation.

Conclusion: Our findings highlight the potential of targeting the AKT/mTOR/p70S6K pathway in promoting oligodendrocyte differentiation and myelin regeneration in neurological disorders such as SCI.

Background: Stroke is a serious disease that threatens human health both in China and worldwide. Identifying and establishing its risk factors are prerequisites for intervention and evaluation of prognosis. Over the years, risk factors, such as age, diabetes, and hypertension, have gradually been established. However, at present, there is no consensus on the influence of sex on the prognosis of ischaemic stroke.

Aims: The aims of our research was to analyse the correlation between sex and poststroke prognosis based on the results of the Third China National Stroke Registry [CNSR-III], as well as the influence of other risk factors that may be confounded by sex on ischaemic stroke and potential interventions.

Methods: The CNSR-III recruited 14146 acute ischaemic stroke [AIS] patients between 2015 and 2018. Our study included 13,972 patients who had complete follow-up information. This research analysed basic information, socioeconomic status, lifestyle habits, medical history, and poststroke prognosis.

Results: There was a conspicuous relationship between sex and functional prognosis, stroke recurrence and all-cause death due to ischemic stroke in univariate analysis. Male stroke patients had a better prognosis than female patients. In multivariate analysis, we found that age, atrial fibrillation [AF], diabetes, hypertension and the severity of stroke had adverse effects on ischemic stroke prognosis. After adjustment for other risk factors, the functional prognosis of female patients at 3 months was worse than that of male patients [odds ratio [OR] 1.16, 95% confidence interval [CI], 1.025- 1.314]. Sex had a nonsignificant association with stroke recurrence at 3 months [hazard ratio [HR] 1.141, 95% CI, 0.975-1.336]. Furthermore, compared to male patients, female stroke patients had a lower cumulative death rate at 12 months [HR 0.777, 95% CI, 0.628-0.963].

Conclusion: Our study identified sex differences in stroke-related disability, recurrence, and death and attempted to explain the causes of these differences. Our study clearly showed that a large proportion of this difference could be attributed to age, socioeconomic factors, lifestyle habits, and medical history, confounded by sex differences rather than sex per se.