Current neurovascular research最新文献

Background: Neuropathic pain originating from a dysfunction in the nervous system is often intractable and chronic. Recently, several studies using nanoparticles suggested a new way to control neuropathic pain. This study intended to explore the potential neuroprotective effect of Cerium Oxide Nanoparticles (CNPs) synthesized by pullulan in neuropathic pain in rats.

Methods: On the right common sciatic nerve of male Wistar rats, the chronic constriction injury (CCI) procedure was used to establish a neuropathic pain model. CNPs were injected into the caudal vein of the rat. Behavioral methods were used to detect mechanical allodynia, cold allodynia, and thermal hyperalgesia in rats. Besides, inflammation factors, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, nitric oxide (NO), and markers of oxidative stress, including Malondialdehyde (MDA) and total thiol, were measured in the spinal cord segment of rats.

Results: In rats with CCI, mechanical allodynia, cold allodynia, and thermal hyperalgesia developed, which improved when the rats were administered CNPs. Spinal cord specimens of CCI rats had elevated inflammation and oxidative stress status (↑IL-1β, ↑TNF-α, ↑NO, ↑MDA) and decreased antioxidative levels (↓total thiol). As a result of CNPs treatment, these changes were reversed in the spinal cord specimens.

Conclusion: CNPs alleviate neuropathic pain by exhibiting antioxidative and anti-inflammatory activities.

Background: Neuroinflammation and oxidative stress after traumatic brain injury (TBI) can further lead to neuronal apoptosis, which plays a crucial role in the process of neuron death. Curcumin, which is derived from the rhizome of the Curcuma longa plant, has multiple pharmacological effects.

Objective: The objective of this study was to investigate whether curcumin treatment has neuroprotective effects after TBI, and to elucidate the underlying mechanism.

Methods: A total of 124 mice were randomly divided into 4 groups: Sham group, TBI group, TBI+Vehicle group, and TBI+Curcumin group. The TBI mice model used in this study was constructed with TBI device induced by compressed gas, and 50 mg/kg curcumin was injected intraperitoneally 15 minutes after TBI. Then, the blood-brain barrier permeability, cerebral edema, oxidative stress, inflammation, apoptosis-related protein, and behavioral tests of neurological function were utilized to evaluate the protective effect of curcumin after TBI.

Results: Curcumin treatment markedly alleviated post-trauma cerebral edema and blood-brain barrier integrity, and suppressed neuronal apoptosis, reduced mitochondrial injury and the expression of apoptosis-related proteins. Moreover, curcumin also attenuates TBI-induced inflammatory response and oxidative stress in brain tissue and improves cognitive dysfunction after TBI.

Conclusion: These data provide substantial evidence that curcumin has neuroprotective effects in animal TBI models, possibly through the inhibition of inflammatory response and oxidative stress.

Apolipoprotein E4 (APOE4) is one of the primary genetic risk factors for late-onset of Alzheimer's disease (AD). While its primary function is to transport cholesterol, it also regulates metabolism, aggregation, and deposition of amyloid-β (Aβ) in the brain. The disruption in the generation and removal of Aβ in the brain is the primary cause of memory and cognitive loss and thus plays a significant role in the development of AD. In several prior genetic investigations, the APOE4 allele has been linked to higher susceptibility to severe acute respiratory syndrome (SARSCoV- 2) infection and COVID-19 mortality. However, information on the involvement of APOE4 in the underlying pathology and clinical symptoms is limited. Due to the high infection and mortality rate of COVID-19 in AD individuals, challenges have been identified in the management of AD patients during the COVID-19 pandemic. In order to provide evidence-based, more effective healthcare, it is critical to identify underlying concerns and, preferably, biomarkers. The risk variant APOE4 imparts enhanced infectivity by the underlying coronavirus SARS-CoV-2 at a cellular level, genetic level, and route level. Here we review existing advances in clinical and basic research on the AD-related gene APOE, as well as the role of APOE in AD pathogenesis, using neurobiological evidence. Moreover, the role of APOE in severe COVID-19 in Alzheimer's patients has also been reviewed.

Background: Previous studies revealed that obstructive sleep apnea (OSA) and smoking, alcohol consumption, and coffee intake are closely related. This study aimed to evaluate the causal effect between these factors and OSA.

Methods: The published genome-wide association study data (GWAS) provided genetic tools. We conducted a univariable two-sample Mendelian Randomization (MR) to estimate the causal effect between smoking initiation, never smoking, alcohol consumption, coffee intake, and coffee consumption with the risk of incidence OSA. Inverse variance weighting (IVW) was used as the main method for effect evaluation, and other MR methods were used for sensitivity analysis. After adjusting for body mass index (BMI), hypertension, and diabetes respectively by multivariable MR (MVMR), we further evaluate the causal effect of these factors on OSA.

Results: Under univariable MR analysis, we observed that smoking initiation was associated with an increased risk of incidence OSA (OR 1.326, 95% CI 1.001-1.757, p =0.049). Never smoking was associated with decreased risk of OSA (OR 0.872, 95% CI 0.807-0.942, p <0.001). Coffee intake and coffee consumption was associated with an increased incidence of OSA (OR 1.405, 95% CI 1.065-1.854, p =0.016) and (OR 1.330, 95% CI 1.013-1.746, p =0.040). Further multivariate MR showed that the causal relationship between never smoking and OSA existed but not coffee consumption, after adjusting for diabetes and hypertension. However, the all results did not support causality after adjusting for BMI.

Conclusion: This two-sample MR study showed that genetically predicted smoking and higher coffee intake are causally associated with an increased risk of OSA.

Background: Autoimmune diseases are associated with cardiovascular and cerebrovascular diseases. However, whether myasthenia gravis (MG) and ischemic stroke (IS) are causally related remains unclear.

Objectives: This study aimed to evaluate potential causal links between MG and IS using bidirectional Mendelian randomization (MR).

Methods: We conducted a two-sample MR analysis to assess the potential associations between MG and IS. Genetic variants associated with MG and IS as well as their subtypes were extracted from genome-wide association studies by meta-analysis. The inverse-variance weighted method was used for the main MR analysis. Sensitivity analyses, including the MREgger, simple mode, simple median, weighted mode, and weighted median approaches were applied to test the robustness of the results.

Results: The MR analyses indicated no causal effects of general MG on IS of all causes (odds ratio [OR] = 0.990, 95% confidence interval [CI]: 0.953-1.029, p = 0.615), large vessel atherosclerosis stroke (OR = 0.943, 95% CI: 0.856-1.039, p = 0.233), cardioembolic stroke (OR = 0.975, 95% CI: 0.867-1.096, p = 0.670), and small vessel occlusion stroke (OR = 1.059, 95% CI 0.974-1.150, p = 0.178). Subgroup analyses indicated no causal effects of early- or late-onset MG on IS and its subtypes (all p > 0.05). The reverse MR analysis showed no significant causal associations of IS on MG (all p > 0.05).

Conclusion: Bidirectional MR analysis did not provide evidence to support a causal relationship between genetically predicted MG and IS, although observational studies have found such a potential link.

Disorders of metabolism affect multiple systems throughout the body but may have the greatest impact on both central and peripheral nervous systems. Currently available treatments and behavior changes for disorders that include diabetes mellitus (DM) and nervous system diseases are limited and cannot reverse the disease burden. Greater access to healthcare and a longer lifespan have led to an increased prevalence of metabolic and neurodegenerative disorders. In light of these challenges, innovative studies into the underlying disease pathways offer new treatment perspectives for Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease. Metabolic disorders are intimately tied to neurodegenerative diseases and can lead to debilitating outcomes, such as multi-nervous system disease, susceptibility to viral pathogens, and long-term cognitive disability. Novel strategies that can robustly address metabolic disease and neurodegenerative disorders involve a careful consideration of cellular metabolism, programmed cell death pathways, the mechanistic target of rapamycin (mTOR) and its associated pathways of mTOR Complex 1 (mTORC1), mTOR Complex 2 (mTORC2), AMP-activated protein kinase (AMPK), growth factor signaling, and underlying risk factors such as the apolipoprotein E (APOE-ε4) gene. Yet, these complex pathways necessitate comprehensive understanding to achieve clinical outcomes that target disease susceptibility, onset, and progression.

Background: To investigate the combined effect of red blood cell distribution width (RDW) and inflammatory biomarkers on in-hospital outcomes of acute ischemic stroke(AIS) patients with thrombolysis.

Methods: 417 AIS patients with thrombolysis were included. The participants were divided into four groups according to the cut-off of white blood cell (WBC) or C reactive protein (CRP) and RDW: LWLR, LWHR, HWLR, and HWHR; or LCLR, LCHR, HCLR, and HCHR (L-low, Hhigh, W-WBC, C-CRP, R-RDW). Logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of in-hospital pneumonia and functional outcome across the four subgroups.

Results: Patients with higher RDW and inflammatory biomarkers levels have the highest risk of in-hospital outcomes. Compared with patients in the LWLR group, the ORs (95% CIs) of those in the HWHR group were 12.16 (4.21-35.14) and 9.31 (3.19-27.17) for in-hospital pneumonia and functional outcome. The ORs (95% CIs) of those in the HCHR group were 6.93 (2.70-17.78) and 3.38 (1.10-10.39) for in-hospital pneumonia and functional outcome, compared with patients in the LCLR group. Simultaneously adding RDW and WBC or CRP to the basic model with established risk factors significantly improved risk discrimination and reclassification for pneumonia and functional outcome (all p <0.05).

Conclusions: Combined RDW and inflammatory biomarkers within 4.5 hours had a better predictive power for in-hospital outcomes of AIS patients with thrombolysis.

Objective: The objective of this study is to study the mechanism of Low frequency electrical stimulation (LFS) in the treatment of drug-resistant epilepsy by regulating the protein kinase A (PKA)-cAMP response element-binding protein (CREB) signaling pathway upstream of gamma aminobutyric acid A (GABA_A) receptor.

Methods: Primary hippocampal neurons were extracted and cultured from fetal rat brains and randomly divided into the normal control group, PKA-CREB agonist group, and PKA-CREB inhibitor group. Drug-resistant epileptic rats were established and randomly divided into the pharmacoresistant group, LFS group, PKA-CREB agonist combined with hippocampal LFS group, and PKA-CREB inhibitor combined with hippocampal LFS group. The normal rats were in the normal control group and drug-sensitive rats were in the pharmacosensitive group. The seizure frequency of epileptic rats was determined using video surveillance. The expression of PKA, CREB, p-CREB, and GABAA receptor subunits α1 and β2 of each group were detected using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting assays.

Results: The in vitro expression levels of PKA, CREB, and p-CREB in the agonist group were significantly higher than those in the normal control group (NRC group), while the expression levels of GABAA receptor subunits α1 and β2 were significantly lower than those in the NRC group. The expression levels of PKA, CREB, and p-CREB in the inhibitor group were significantly lower, while the expression levels of GABAA receptor subunits α1 and β2 were significantly higher than those in the NRC group. The in vivo seizure frequency was significantly lower in the LFS group than in the pharmacoresistant group (PRE group). Compared to the LFS group, the seizure frequency and the expression levels of PKA, CREB, and p-CREB in the rat hippocampus were significantly higher, and the expression levels of GABA_A receptor subunits α1 and β2 were significantly lower in the agonist group. The results in the inhibitor group were exactly the opposite of those in the agonist group.

Conclusion: The PKA-CREB signaling pathway is involved in the regulation of GABAA receptor subunits α1 and β2. In addition, LFS plays an important role in increasing GABAA receptor expression by regulating the PKA-CREB signaling pathway.

Background: Cerebral small vessel disease (CSVD) refers to a common cerebrovascular disease and white matter hyperintensities (WMHs) constitute a typical feature of CSVD. However, there has not been a large number of studies investigating the relationship between lipid profile components and WMHs.

Methods: Altogether, 1019 patients with CSVD were enrolled at the First Affiliated Hospital of Zhengzhou University between April 2016 to December 2021. Baseline data were collected for all patients, including demographic characteristics and clinical data. WMH volumes were evaluated by two experienced neurologists using the MRIcro software. Multivariate regression analysis was used to investigate the relationship among the severity of WMHs, blood lipids and common risk factors.

Results: Altogether, 1019 patients with CSVD were enrolled, including 255 in the severe WMH group and 764 in the mild WMH group. After including age, sex and blood lipids to construct a multivariate logistic regression equation, we observed that the severity of WMHs was independently predicted by low-density lipoprotein (LDL), homocysteine level and history of cerebral infarction.

Conclusion: We used WMH volume, a highly accurate measure, to assess its relationship with lipid profiles. The WMH volume increased with a decrease in LDL. This relationship was more significant, especially among the subgroups of patients aged <70 years and men. Patients with cerebral infarction and higher homocysteine levels were more likely to have higher WMH volumes. Our study has provided a reference for clinical diagnosis and therapy, especially for discussing the role of blood lipid profiles in the pathophysiology of CSVD.

Objective: White matter hyperintensity (WMH) is related to the increased risk of ischemic stroke. It is unclear if H-type hypertension (H-type HBP) is associated with periventricular WMH (PWMH) and deep WMH (DWMH) of acute ischemic stroke. This study investigated the correlation between H-type HBP and the severity of PWMH and DWMH in acute ischemic stroke.

Methods: Consecutive patients with acute ischemic stroke were included in this cross-sectional observational study. The patients were divided into the following groups: the normal group, the simple hypertension group (Simple HBP), the simple hyperhomocysteinemia group (Simple HHcy) and the H-type HBP group. MR imaging and relevant clinical variables were obtained from the medical records. PWMH and DWMH were rated by using the Fazekas scale (score 0-3). All patients were defined to have moderate-severe PWMH or DWMH (score 2-3) and no or mild group (score 0-1). Multivariate binary logistic regression analysis was performed to determine the relationship between H-type HBP and the severity of PWMH and DWMH.

Results: Among 542 patients, 227 had moderate-severe PWMH and 228 had moderate-severe DWMH. Compared to the no or mild group, patients with moderate-severe PWMH (median age: 73 vs. 63 years) and DWMH (median age: 70 vs. 65.5 years) were older. Compared to the no or mild group, moderate-severe PWMH and DWMH were associated with a history of ischemic stroke (moderate-severe PWMH vs. no or mild group 20.7% vs. 11.7%, p = 0.004；moderatesevere DWMH vs. no or mild group 20.2% vs. 12.1%, p = 0.010); We found that H-type HBP was an independent risk factor for PWMH (OR 2.64, 95% CI 1.34-5.21) and DWMH (OR 3.64, 95% CI 1.82-7.26) after adjusting for the effect of relevant risk factors.

Conclusion: This study suggests that H-type HBP is associated with the severity of PWMH and DWMH in acute ischemic stroke patients, which deserves further prevention measures.