Current neurovascular research最新文献

Introduction: An essential component of the endocannabinoid system, cannabinoid receptor type 1 (CB1) is primarily expressed in the central nervous system, where it regulates several neurophysiological activities. Neurotransmitter release, synaptic plasticity, mood modulation, and cognitive processes are all influenced by CB1 receptors. The CB1 receptor is closely linked to a wide range of brain-related disorders, and regulating its activity may be a way to treat several brain-related diseases.

Methods: Literature search across Google Scholar, Scopus, PubMed, and Web of Science, covering publications from 1985 to 2025, aimed to gather extensive information on the pharmacological role of the CB1 receptor in various brain illnesses. Using keywords such as "CB1," "Brain," "Epilepsy," "Alzheimer's," "Parkinson's disease," "Neuroprotection," and "Neurodegeneration," this review consolidates existing knowledge and identifies potential avenues for future research.

Results: This study incorporates pre-clinical evidence and highlights the involvement of the CB1 receptor in etiologies, symptoms, and treatments related to distinct brain-related disorders.

Discussion: Potential treatment strategies that target the endocannabinoid system and the intricate relationship between CB1 receptor activity and its consequences in several brain disorders, including Parkinson's disease, Huntington's disease, Alzheimer's disease, depression, anxiety, etc., have been discussed. Additionally, the difficulties and disputes related to CB1 receptor modulation, including the contradictory actions of CB1 receptor agonists and antagonists, are also addressed.

Conclusion: The CB1 receptor is a promising therapeutic target for brain disorders due to its key role in regulating various physiological functions in the CNS, suggesting potential for the treatment of several brain disorders.

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: As the fifth vital sign, peripheral oxygen saturation (SpO₂) remains understudied in acute ischemic stroke (AIS) patients undergoing mechanical thrombectomy (MT). This study aimed to investigate the association between perioperative SpO₂ levels and malignant brain edema (MBE) development in MT-treated AIS patients.

Methods: We retrospectively analyzed consecutive stroke patients who achieved successful recanalization through MT between May 2017 and February 2023. Noninvasive SpO₂ measurements were obtained pre- and postoperatively. Regression analysis was carried out to assess the association between preoperative, postoperative, and combined SpO₂ (stratified into four groups based on SpO₂ median values: HL, high preoperative/low postoperative; LL, low/low; HH, high/high; and LH, low/high) and MBE. DeLong's test was conducted to compare the predictive value of combined SpO₂ with that of preoperative or postoperative SpO₂ alone.

Results: Among 376 patients, 84 (22.34%) patients developed MBE. Although preoperative SpO₂ was not independently associated with MBE (OR: 0.88; 95% CI: 0.78-1.00; p =0.0583), postoperative SpO₂ was independently correlated with MBE (OR: 1.48; 95% CI: 1.01-2.18; p =0.0440). The LH group demonstrated 5.33-fold higher MBE risk versus HL (95% CI: 1.80- 15.82; P_trend =0.0043). Combined SpO₂ assessment outperformed preoperative measurements alone (0.6316 vs. 0.5478, p =0.0382) and trended towards superiority over postoperative values (0.6316 vs. 0.6022, p =0.0541).

Discussion: Preoperative and postoperative SpO₂ exhibit divergent impacts on MBE, likely reflecting distinct pathophysiology. Preoperative hypoxia may exacerbate ischemic core expansion, while postoperative hyperoxia could augment reperfusion injury via reactive oxygen species. The LH pattern (low pre-/high post-MT SpO₂) highlights a high-risk phenotype for MBE.

Conclusion: Preoperative and postoperative SpO₂ differentially influence MBE development, suggesting distinct pathophysiological mechanisms during thrombectomy phases.

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: Olfactory epithelium (OE) comprises diverse cell types, including olfactory sensory neurons (OSNs), 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 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.

Background: Bilirubin plays a crucial role in the pathophysiological processes of strokes. However, the relationship between serum bilirubin levels and the prognosis of aneurysmal subarachnoid hemorrhage (aSAH) remains unexplored. This study aims to investigate the association between serum bilirubin levels and the mortality rate of aSAH patients.

Methods: 695 aSAH patients were included to analyze the relationship between direct bilirubin (DBil), indirect bilirubin (IDBil), total bilirubin (TBil), and mortality. The univariate and multivariate logistic regression were conducted to discover risk factors for the mortality of aSAH. The restricted cubic spline (RCS) was used to show the correlation between DBil, IDBil, TBil, and mortality. A logistic regression predictive model was developed by incorporating significant factors in the multivariate logistic regression. The receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of serum bilirubin and the developed predictive model.

Results: 139 aSAH patients suffered death, with a mortality of 20.0%. Non-survivors had older age (p =0.007), lower GCS (p <0.001), higher Hunt Hess (p <0.001), and mFisher (p <0.001). Both DBil (p <0.001) and TBil (p =0.011) were significantly higher among non-survivors. While the IDBil did not show a difference between survivors and non-survivors. The multivariate analysis found age (p =0.111), Glasgow Coma Scale (p =0.005), white blood cell (p <0.001), glucose (p =0.004), DBil (p =0.001), delayed cerebral ischemia (p <0.001) were significantly related with the mortality of aSAH. A logistic regression predictive model for mortality was developed incorporating these five factors, which had an area under the ROC curve (AUC) of 0.876. The AUC of DBil, IDBil, and TBil for predicting mortality was 0.607, 0.570, and 0.529, respectively.

Conclusion: Serum DBil level is positively associated with the mortality risk of aSAH. The predictive model incorporating DBil is beneficial for clinicians to evaluate the mortality risk of aSAH and adopt personalized therapeutics.

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 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 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.

Background: This study aims to explore the correlation between body composition, encompassing factors such as muscle mass and fat distribution, and gait performance during both single-task walking (STW) and dual-task walking (DTW) in patients diagnosed with cerebral small vessel disease (CSVD).

Methods: The data of hospitalized patients diagnosed with CSVD, including cadence, stride time, velocity and stride length, as well as information on variability, asymmetry and coordination during both STW and DTW, were assessed. The number of falls reported by each participant was also assessed.

Results: A total of 95 CSVD patients were assessed, and the results showed that individuals with low appendicular skeletal muscle mass (ASM), which includes both the low ASM group and the combination of low ASM and high body fat (BF) group, had reduced velocity or cadence, shortened stride length, and prolonged stride time across all walking modalities compared to the control group. Only the combination of the low ASM and high BF group exhibited a deterioration in the coefficient of variation (CV) for all basic parameters and the Phase Coordination Index (PCI) compared to the control group across all walking patterns. Conversely, patients in the high BF group displayed a decline in basic parameters, primarily during cognitive DTW. Concurrently, the high BF group showed a significant increase in the CV and the PCI compared to the control group only during cognitive DTW. Furthermore, regardless of gender, both ASM and BF independently correlated with the occurrence of falls.

Conclusions: CSVD patients with varying body compositions could allocate different levels of attention to their daily walking routines.