Current neurovascular research最新文献

Objective: This study aims to identify risk factors for symptomatic intracerebral hemorrhage (ICH) in patients with old cerebral infarction.

Methods: A retrospective cohort study was conducted at Jining First People's Hospital between January 2022 and May 2024, including 287 individuals with a history of prior cerebral infarction. Study participants were classified into two groups based on the presence of symptomatic hemorrhage: those with ICH (n = 96) and those without ICH (n = 191). Logistic regression analysis was employed to identify risk factors associated with cerebral hemorrhage occurring after cerebral infarction in this population.

Results: The incidence of ICH among individuals with prior cerebral infarction was 33.48% (96/287 cases). Univariate regression analysis revealed significant differences between the ICH and the non-ICH groups in alcohol consumption, hypertension, hyperlipidemia, statin therapy, antiplatelet therapy, systolic blood pressure, diastolic blood pressure, glycosylated hemoglobin, platelet-to-lymphocyte ratio, and cerebral microbleeds (CMBs). Multivariate logistic regression analysis revealed that CMB, alcohol consumption, hyperlipidemia, and statin treatment were independent predictors of ICH in individuals with prior cerebral infarction. Additionally, CMB severity was significantly positively correlated with ICH occurrence.

Conclusion: The development of ICH in individuals with prior cerebral infarction is influenced by multiple factors. Effective management of CMBs, control of hyperlipidemia, alcohol abstinence, and careful adjustment of statin therapy are critical for preventing ICH. CMB severity emerges as a particularly strong predictor of ICH risk.

Introduction: Acute ischemic stroke (AIS) is linked to dysregulated immuneinflammatory responses. The platelet-to-high-density lipoprotein cholesterol ratio (PHR) and fibrinogen-to-high-density lipoprotein cholesterol ratio (FHR) have emerged as potential systemic inflammation biomarkers. This study evaluated the association among PHR, FHR, and 6- month functional outcomes in patients with large-vessel occlusion-related AIS (AIS-LVO) treated with endovascular therapy (EVT).

Methods: This single-center retrospective study included AIS-LVO patients undergoing EVT at Beijing Chaoyang Hospital (Jan 2023-May 2024). Demographic, clinical, and preoperative laboratory data were collected, and 6-month outcomes were assessed using the modified Rankin Scale (mRS). Multivariate logistic regression and operating characteristic curves (ROC) analyses were used to evaluate the predictive value of PHR and FHR, with subgroup analyses performed across clinical strata.; Results: A total of 46.76% (123/263) of patients had unfavorable outcomes at the 6-month follow- up. Multivariate analysis revealed that higher preoperative PHR (adjusted odds ratio [aOR] = 1.015; 95% confidence interval [CI], 1.009-1.020; P < 0.001) and FHR (aOR = 1.007; 95% CI, 1.004-1.010; P < 0.001) were independent risk factors for poor functional outcomes at 6 months post-EVT.

Discussion: Findings align with prior links between inflammatory biomarkers and AIS prognosis, extending to EVT-treated AIS-LVO. The utility of PHR/FHR may reflect integration of the prothrombotic-anti-inflammatory pathway, with limitations, including a single-center design and a lack of dynamic inflammatory monitoring.

Conclusion: PHR (PHR AUC=0.727, 95% CI: 0.667-0.788) and FHR (AUC=0.716, 95% CI: 0.655-0.777) independently predict 6-month outcomes, with elevated levels linked to poor prognosis. These markers may reflect synergistic roles in post-stroke inflammation and thrombosis, offering potential for integration into individualized prognostic models to guide early intervention.

Introduction: The impact of integrated glycemic indices on acute ischemic stroke (AIS) prognosis remains unclear. This study assessed the correlation between the stress hyperglycemia ratio (SHR) and the glucose-to-albumin ratio (GAR), mediated by the systemic inflammatory response index (SIRI), and their effects on the 90-day prognosis of AIS patients.

Methods: Between January 2017 and November 2023, 5,313 AIS patients were registered in the Nanjing Stroke Registry. The links are as follows: SHR, GAR, and neurological deficits after AIS were statistically evaluated via univariate logistic regression analysis (ULRA) and multivariate logistic regression analysis (MLRA). Subgroup analyses were conducted to confirm the stability of the outcome. Finally, a mediation analysis of the SIRI was undertaken to investigate the relationship between hyperglycemia status and the outcomes of AIS.

Results: Depending on the modified Rankin scale (mRS) score, there were 815 patients with a poor outcome and 4,498 patients with a better outcome during the mean 90-day follow-up period. ULRA and MLRA revealed that SHR and GAR were strongly related to adverse stroke outcomes after adjusting for covariates. The SHR (Model III: OR = 1.12, 95% CI, (1.03-1.22), p = 0.006). GAR (Model III: OR = 1.22, 95% CI, 1.12-1.34, p < 0.001). SIRI mediated 28.4% (SHR) and 17.2% (GAR) of these effects.

Conclusion: This study highlighted that SHR and GAR were positively correlated with adverse clinical and mortality outcomes in AIS patients at 90 days, partly mediated by the SIRI.

Introduction: Although ischemic stroke is associated with complex changes in the autonomic nervous system, the circadian patterns of heart rate (HR) and heart rate variability (HRV) in wake-up stroke (WUS) remain poorly understood. This study compared 24-hour heart rate and HRV patterns between patients with and without WUS.

Methods: This retrospective observational case-control study involved 104 patients with acute ischemic stroke (9 WUS, 95 non-WUS). HRV analysis was performed using a 14-day continuous electrocardiography patch monitor. Time- and frequency-domain HRV metrics were calculated, and 24-hour differences were assessed using generalized additive mixed models (GAMMs), adjusting for confounders.

Results: WUS patients had significantly higher HRs (80.60 ± 12.49 vs. 73.22 ± 14.49 beats per minute, P < 0.001) and lower HRV-measured by SDNN (28.06 ± 21.68 vs. 39.70 ± 25.73 milliseconds, P < 0.001), RMSSD (15.78 ± 12.49 vs. 22.16 ± 19.22 milliseconds, P < 0.001), and pNN50 (1.03% ± 2.78% vs. 2.61% ± 5.15%, P < 0.001)-than non-WUS patients. GAMMs indicated that patients with WUS experienced significant autonomic dysregulation, characterized by higher HRs, lower HRV, and altered circadian rhythms compared to those with non-WUS. These differences were particularly evident during the early morning hours.

Discussion: WUS patients exhibited distinct 24-hour HR and HRV profiles, characterized by higher HRs and reduced autonomic variability compared to non-WUS patients. These differences align with patterns typically associated with lower parasympathetic activity rather than elevated sympathetic tone.

Conclusion: WUS is associated with impaired autonomic regulation and disrupted circadian patterns of HR and HRV.

Introduction: The objective of this study was to investigate the effects of 3',4'- dihydroxyflavonol (DiOHF) on oxidative and antioxidant systems in kidney tissue and on renal function as distant organ damage following brain ischemia-reperfusion.

Methods: This study was conducted on 28 male Wistar-Albino rats, which were divided into four groups: Control, Sham, Ischemia-Reperfusion (I/R), and Ischemia-Reperfusion + DiOHF. Kidney tissue samples were collected to analyze malondialdehyde (MDA) and glutathione (GSH) levels. Additionally, concentrations of electrolytes (Ca, Cl, Na, K, and P), as well as urea, uric acid, creatinine, and urinary microprotein levels, were measured.

Results: Brain ischemia-reperfusion led to increased malondialdehyde (MDA) levels in both the kidney medulla and cortex, indicating oxidative stress in these distant organs, while glutathione (GSH) levels were suppressed. Additionally, ischemia-reperfusion caused elevations in blood and urine concentrations of urea, uric acid, creatinine, and urinary microproteins.

Discussion: This experimental model significantly elevated urea, uric acid, and creatinine levels, key indicators of kidney function, and similarly increased urinary microprotein loss. While our study demonstrates the detrimental effects of focal brain ischemia-reperfusion on kidney function as a distant organ, further research is needed to investigate its impact on other organs to gain a more comprehensive understanding of distant organ damage.

Conclusion: Results from this experimental model indicate that cerebral ischemia-reperfusion in rats suppresses the antioxidant system and increases oxidative stress in kidney tissue, leading to impaired renal function. However, a 1-week DiOHF treatment mitigated this damage by enhancing the antioxidant defense system.

Introduction: Anandamide (AEA), an endocannabinoid, has demonstrated analgesic and anti-inflammatory properties in various experimental models. However, the mechanisms underlying its role in neuropathic pain and inflammation remain unclear.

Methods: Carrageenan-induced inflammation and Chronic Constriction Injury (CCI) were used to model inflammatory and neuropathic pain in Wistar rats. Behavioral tests (e.g., paw edema, mechanical and thermal hyperalgesia), hematological and biochemical analyses, and molecular studies (mRNA expression of AEA pathway enzymes) were conducted to evaluate AEA's therapeutic potential.

Results: Anandamide significantly reduced paw edema and alleviated pain behaviors in CCI rats in a dose-dependent manner. It normalized hematological and biochemical markers and decreased levels of oxidative stress indicators (MDA, nitrite). mRNA analysis revealed upregulation of AEA degradation enzymes following CCI, indicating disrupted endocannabinoid signaling.

Discussion: AEA's analgesic and anti-inflammatory actions appear to be mediated through CB1 receptor activation and modulation of ATP-sensitive potassium channels. The observed improvements in biochemical and behavioral markers suggest its efficacy in modulating neuroinflammation and neuropathic pain.

Conclusion: Anandamide demonstrates significant potential as a therapeutic agent in managing neuropathic and inflammatory pain. Further studies are warranted to elucidate its mechanisms and optimize its clinical applicability.

Introduction: Epilepsy is a neurological disorder characterized by recurrent seizures that can cause long-standing disturbance of normal brain function. It may adversely affect academic performance, behavior, emotional adjustment, social adaptability, and overall development in children. Neurotrophic factors and inflammatory markers are believed to play key roles in the pathogenesis of epilepsy. This study evaluated the effect of levetiracetam monotherapy and its combination with phenytoin on serum brain-derived neurotrophic factor (BDNF) levels, Interleukin-2 (IL-2) levels, and social adaptability/development in children with epilepsy.

Methods: Children with epilepsy, aged 1 to 12 years, were given levetiracetam monotherapy (n=30) and combination therapy of levetiracetam and phenytoin (n=30) for 20 weeks. Healthy controls (n=30) were also included. Serum BDNF and IL-2 levels were assessed at baseline and 20 weeks, along with social adaptability and development, using the Vineland Social Maturity Scale (VSMS) and Developmental Screening Test (DST) scores, respectively.

Result: Pretreatment, serum BDNF and IL-2 levels were significantly (p <0.001) lower and higher respectively, in both treatment groups compared to controls. After 20 weeks, BDNF and IL-2 levels were significantly (p <0.001) increased and decreased, respectively, in the monotherapy group and combination therapy group. VSMS and DST scores improved significantly (p <0.001).

Discussion: The findings suggest that levetiracetam and its combination with phenytoin modulate neurotrophic and inflammatory pathways in pediatric epilepsy, with parallel improvements in social and developmental outcomes.

Conclusion: Levetiracetam monotherapy and its combination therapy with phenytoin increased serum BDNF levels, decreased IL-2 levels, and improved VSMS and DST scores in pediatric epilepsy patients, suggesting that these treatments influence epileptogenesis.

Introduction: This study investigated the neuroprotective mechanisms of ischemic postconditioning (IPostC) in ischemic stroke, focusing on ferroptosis and the regulatory role of the ferroptosis-related gene NADPH oxidase 4 (NOX4).

Methods: Male C57BL/6 mice underwent 45-minute middle cerebral artery occlusion (MCAO), followed by IPostC (three 15s/30s ischemia/reperfusion cycles after initial 2-minute reperfusion). RNA sequencing, combined with the least absolute shrinkage and selection operator (LASSO) and random forest machine learning, quantitative real-time PCR (qRT-PCR), infarct size measurement, and neurological tests, was used to identify ferroptosis-related genes and validate their roles in IPostC-induced neuroprotection.

Results: RNA sequencing revealed that 42 ferroptosis-associated differentially expressed genes underlie the neuroprotective effects of IPostC. Among them, NOX4 emerged as a central pathogenic regulator through least absolute shrinkage and selection operator (LASSO) and random forest machine learning analyses. IPostC reduced cerebral infarct size and improved foot-fault rate compared to MCAO mice. Notably, the ferroptosis inducer Erastin abolished the protective effects of IPostC. qRT-PCR validation revealed that IPostC downregulated NOX4 mRNA expression compared to MCAO controls, while Erastin upregulated NOX4 expression. In addition, pharmacological inhibition of NOX4 with GLX351322 further reduced its mRNA expression, decreased infarct size, and improved neurological function, further confirming its critical role in mediating ferroptosis-driven brain injury after ischemic stroke.

Discussion: The inhibition of ferroptosis-associated gene NOX4 by IPostC may be a novel mechanism for treating ischemic stroke.

Conclusion: Our study indicates that IPostC attenuates cerebral ischemic injury by suppressing ferroptosis-associated gene NOX4.

Introduction: This study aimed to analyze the global, regional, and national burden and trends of stroke related to high consumption of processed meat from 1990 to 2021, using data from the Global Burden of Disease (GBD) Study 2021.

Methods: An observational trend analysis was conducted using data from the GBD Study 2021. Age-standardized rates for deaths and disability-adjusted life years (DALYs) were calculated using the world standard population. Estimated annual percentage change (EAPC) was assessed using linear regression models.

Results: From 1990 to 2021, the global age-standardized death rate due to diet high processed meat-related stroke decreased from 0.80 per 100,000 (95% UI: 0.18 to 1.43) to 0.27 per 100,000 (95% UI: 0.06 to 0.46), with an EAPC of -4.23% (95% UI: -4.54 to -3.92). The age-standardized DALY rate also declined from 14.16 per 100,000 (95% UI: 3.19 to 25.49) to 5.20 per 100,000 (95% UI: 1.21 to 9.33), with an EAPC of -4.00% (95% UI: -4.34 to -3.67). Significant disparities were observed across regions and socioeconomic strata, with higher burdens in high-middle SDI regions. Females consistently had higher death and DALY rates and counts than males.

Discussion: The study reveals a significant decline in both mortality and DALYs associated with a diet high in processed meat-related stroke over the three decades.

Conclusion: Our study highlighted the effectiveness of public health interventions. However, disparities persist across regions and socioeconomic strata, emphasizing the need for targeted and context-specific strategies to mitigate the burden of stroke related to high processed meat intake.

Introduction: Olfactory epithelium (OE) comprises diverse cell types, including olfactory sensory neurons, supporting cells, and basal stem cells. While interleukin (IL)-4 is a key mediator in type 2 inflammation, its regulatory role in OE remains unclear. The current study aimed to explore the role of IL-4 in olfactory epithelial cells.

Methods: Using an olfactory epithelial organoid model, the impacts of IL-4 on different cell types were assessed by performing qPCR, immunofluorescence staining, and EdU incorporation assays. Calcium imaging was performed to assess the influence of IL-4 on olfactory sensory neurons (OSNs), while Alcian Blue-Periodic Acid-Schiff (AB-PAS) staining was used to analyze mucin secretion in the organoids.

Results: IL-4 significantly promoted the proliferation of globular basal cells (GBCs) in basal cells, induced homeostasis of mature OSNs, and maintained the normal function of OE. However, IL-4 notably downregulated GAP43 expression in immature OSNs. Additionally, IL-4 enhanced mucin secretion in the OE.

Discussion: This study found that IL-4 promoted the differentiation of OE cells by stimulating the proliferation of GBCs and enhancing mucin secretion, while maintaining the normal function of mature olfactory neurons. Further clinical studies are needed to validate these results.

Conclusion: This study revealed the role of IL-4 in OE, providing novel insights into the mechanisms of IL-4 in inflammatory conditions.