Neurological Research最新文献

Objective: We aimed to construct a prediction model of silent brain infarction (SBI) based on ultrasonic features of carotid plaques and resistance of intracranial blood flow.

Methods: A retrospective cohort study was designed to collect patients' clinical data from the database of our hospital. An SBI group was set up to include 168 SBI patients confirmed by cranial magnetic resonance imaging (MRI) between January 2022 and December 2024, and a non-SBI group was created to enroll 168 patients with carotid plaques. The influencing factors for SBI were identified through multivariate analysis. A prediction model of SBI was established and verified for its efficiency.

Results: Regarding the parameters of intracranial blood flow resistance, the middle cerebral artery pulsatility index (MCA-PI) and middle cerebral artery resistance index (MCA-RI) were higher in the SBI group than in the non-SBI group (p < 0.05). The ultrasonic features of carotid plaques [plaque thickness and carotid intima-media thickness (CIMT)] as well as the parameters of intracranial blood flow resistance (MCA-PI and MCA-RI) were risk factors for SBI (odds ratio > 1, p < 0.05). The calibration curve resembled the straight line Y = X, the model was well-calibrated, and the concordance index was 0.889, suggesting a good discrimination of the model.

Conclusion: The SBI prediction model constructed on the basis of ultrasonic features of carotid plaques (plaque thickness and CIMT) plus parameters of intracranial blood flow resistance (MCA-PI and MCA-RI) has potential clinical value.

Objective: This study evaluated endogenous circadian rhythm characteristics in mild acute ischemic stroke (AIS) patients, their impact on prognosis, and underlying mechanisms.

Methods: AIS patients were selected from the Department of the Second Affiliated Hospital of Soochow University, and volunteers were recruited as the control group. A phased sampling strategy was used: first, salivary melatonin was collected at 6 daily time points (0:00, 3:00, 6:00, 12:00, 18:00, 21:00) to assess secretion trends; then, hourly samples from 19:00-23:00 were taken to calculate dim light melatonin onset (DLMO). Three-month follow-up was done, and AIS patients were grouped by DLMO to explore links between circadian rhythm and plasma inflammatory markers.

Results: A total of 255 participants were enrolled in this study, including 182 AIS patients and 73 controls. The melatonin amplitude and peak were lower throughout the day in the AIS group, with a delayed peak secretion time. DLMO, Post-DLMO surge and AUC30 in the AIS group showed a delayed trend. Multivariate logistic regression analysis indicated that DLMO was an independent risk factor for prognosis (p = 0.009). The HIF-1α level in the Delayed DLMO group was higher than that in the Advanced DLMO group (p = 0.004).

Conclusion: In mild AIS patients, the endogenous melatonin secretion peak decreased, and the time to reach the peak was delayed. A delayed endogenous circadian rhythm might be an independent risk factor for poor prognosis in mild AIS patients, and HIF-1α might be involved in this process.

Objective: The Middle East and North Africa (MENA) region faces a critical neurointervention workforce shortage, with an estimated 115,000-130000 preventable deaths annually from treatable neurovascular conditions. We quantified training capacity, service availability, and implementation barriers across 19 countries encompassing 688.2 million inhabitants.

Methods: We conducted a cross-sectional survey of 168 eligible hospitals with 24-hour emergency services, neuroimaging capability, and ≥100 annual neurovascular admissions between May-August 2024. Primary outcomes were Neurointervention Training Access (annual fellowship positions/population-based demand using 2.5 operators per million standard) and Neurointervention Operator Availability (current operators/regional requirements). Multivariable regression identified training capacity predictors.

Results: Among 131 responding institutions (78%response rate), current capacity reached only 19.1% of required neurointerventionists for the region. Training capacity met 4.4%of projected needs, varying from 12.1%in high-income to 0%in low-income countries (p < 0.001). While 80.9% of hospitals performed neurointervention procedures, only 33.6% qualified as comprehensive centers. Among comprehensive centers, 72.7% hosted fellowship programs and 68.2%maintained 24/7 coverage. Significant predictors of higher training capacity included per-capita GDP (β = 0.012, p < 0.001), formal certification pathways (β = 0.285, p = 0.002), and emergency medical services protocols (β = 0.252, p = 0.01). Primary barriers were funding limitations (82.4%), equipment shortages (70.2%), and faculty scarcity (65.6%). Current training infrastructure produced 96 annual graduates against a projected regional deficit of 1434specialists.

Discussion: The MENA neurointervention capacity meets less than 20% of population needs, with pronounced socioeconomic disparities resulting in substantial preventable mortality and disability. Strategic expansion to 28 regional training hubs producing 171 annual fellows may achieve workforce adequacy within 8.4 years, requiring coordinated international investment and policy reform.

Objective: This investigation assessed the predictive value of serum soluble E-selectin (sE-selectin) and C motif chemokine ligand 5 (CCL5) for delayed cerebral edema (DCE) following hematoma removal in patients with hypertensive intracerebral hemorrhage (HICH).

Methods: The study retrospectively included 260 patients with HICH who underwent neuroendoscopic hematoma removal at The Central Hospital of Yongzhou (Yongzhou Hospital Affiliated to University of South China), categorizing them into DCE and Non-DCE groups. General baseline data were collected and preoperative serum sE-selectin and CCL5 levels were measured. The correlation between serum sE-selectin and CCL5 levels was analyzed and the risk factors for DCE after neuroendoscopic hematoma removal in patients with HICH were identified. Receiver operating characteristic (ROC) curves were plotted to analyze the predictive value of serum sE-selectin and CCL5 alone and in combination for DCE.

Results: Serum sE-selectin and CCL5 levels were higher in the DCE group than in the Non-DCE group. There was a moderate positive correlation between serum sE-selectin and CCL5 levels in patients with HICH. Elevated serum sE-selectin and CCL5 levels were independent risk factors for DCE after neuroendoscopic hematoma removal in patients with HICH. The predictive efficacy for DCE after neuroendoscopic hematoma removal in HICH patients was higher when serum sE-selectin and CCL5 were used in combination. Higher sE-selectin or CCL5 increased the incidence of DCE after neuroendoscopic hematoma removal in patients with HICH.

Conclusion: In patients with HICH who experienced DCE following neuroendoscopic hematoma removal, serum sE-selectin and CCL5 are higher, and both markers could help predict DCE.

Objectives: Previous research has shown that melatonin (Mel) can alleviate hypoxic-ischemic brain damage (HIBD) in newborns. The roles of Mel on neurovascular unit (NVU) after HIBD and the mechanisms were explored in this study. Methods: The combination of multiparametric magnetic resonance imaging (MRI) techniques and various histology experiments was utilized to observe the impacts of Mel on the NVU in the damaged cerebral cortex of neonatal rats. Especially, water extraction with phase contrast arterial spin tagging (WEPCAST)-MRI was used to monitor the changes in blood-brain barrier (BBB) permeability to water in neonatal rats with HIBD.

Results: MRI showed that abnormal signals and permeability surface area volume (PS) both decreased after Mel treatment. Various histology results also revealed that Mel treatment alleviated NVU destruction and attenuated MT1 receptor deficiency. Western blotting showed MMP-9 levels in Mel group were significantly decreased at all time points post-hypoxia ischemia (HI). In addition, western blotting and immunohistochemistry (IHC) were utilized to examine the impacts of Mel treatment on the tight connection and key molecules of AKT/GSK-3β/CREB pathway. The results showed that the expressions of Claudin-5, ZO-1, p-Akt, p-GSK-3β, and p-CREB on the damaged side in the Mel+MK2206 group was lower than those in Mel group, while the MMP-9 level was significantly higher.

Conclusion: Multiparametric MRI techniques can monitor the changes of brain microstructure and BBB permeability in neonatal rats with HIBD in vivo at early stage. Mel administration can reduce the NVU injury in neonatal rats with HIBD via activating AKT/GSK-3β/CREB pathway.

Objectives: To evaluate the feasibility and safety of passive upright positioning (PUP) using a standing bed in neurocritically ill patients.

Methods: In this single-center prospective pilot study (July 2019-June 2021), 35 ICU patients underwent upright positioning at 30°, 60°, and 80° using a standing bed. Vital signs, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were measured at 10 minutes before (T0), 10 minutes after (T1), and 2 hours after (T2) initiation. Respiratory mechanics were recorded in ventilated patients. All patients received sedation without neuromuscular blockade. Adverse events were closely monitored. The study was designed as a pilot feasibility investigation of a non-pharmacological mobilization technique and was therefore not registered at the time; prospective trial registration will be incorporated in future confirmatory studies.

Results: Among the 35 patients (mean age 60.9 ± 13.1 years), vital signs including SBP, DBP, MAP, HR, and RR showed statistically significant changes across time points (p < 0.05), but remained within physiological ranges. ICP decreased from 9.04 ± 1.99 mmHg at T0 to 8.33 ± 1.78 mmHg at T2 (p = 0.002). CPP remained stable (p = 0.006). Expiratory resistance (RE) declined significantly (p = 0.034), while Cstat, RI, and PRx remained unchanged. Adverse events occurred in 10 of 94 sessions (10.63%), with two EVD dislodgements (2.13%) requiring surgical repositioning, corresponding to 6% of patients. Other events were transient or managed conservatively.

Conclusions: PUP using a standing bed appears to be a feasible and well-tolerated intervention in neurocritically ill patients. These findings support further investigation in larger controlled studies.

Objective: To investigate the association between herpes simplex virus type 2 (HSV-2) infection and 12-month recurrence of acute ischemic stroke (AIS).

Methods: A prospective cohort study was conducted, enrolling 286 patients with AIS from January 2019 to December 2023. Serum HSV-2-immunoglobulin M (IgM) levels were measured upon admission. Based on these levels, patients were categorized into two groups: the HSV-2-IgM (+) group, consisting of 72 patients, and the HSV-2-IgM(-) group, with 214 patients. Follow-up lasted 12 months, and the primary outcome was stroke recurrence. Logistic regression models were employed to evaluate whether HSV-2-IgM positivity was an independent predictor of AIS recurrence. Additionally, receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off value of serum HSV-2-IgM concentration for predicting AIS recurrence.

Results: The recurrence rate of AIS was significantly higher in the HSV-2-IgM (+) group compared to the HSV-2-IgM (-) group (p = 0.0016). Multivariate Logistic regression analysis indicated that HSV-2-IgM positivity was an independent risk factor for AIS recurrence. Moreover, the 12-month recurrence risk for AIS patients with HSV-2-IgM positivity was approximately four times higher than that of patients with HSV-2-IgM negativity (adjusted odds ratio [OR] = 4.3, 95% confidence interval [CI]: 2.26 - 9.43, p = 0.0002). Furthermore, the area under the ROC curve for HSV-2-IgM was 0.758, suggesting that a serum HSV-2-IgM concentration of 4.135 PEIU/ml could serve as a threshold for predicting ischemic stroke recurrence.

Conclusion: This study reveals that HSV-2-IgM positivity significantly increases the risk of AIS recurrence within 12 months. Additionally, a serum HSV-2-IgM concentration of 4.135PEIU/ml can be utilized as a reference indicator for predicting stroke recurrence.

Background: Breakthrough cancer pain (BTcP) lacks representative animal models. The roles of spinal excitatory amino acid transporters (EAATs) in BTcP remain unclear.

Methods: We established a modified BTcP mouse model using lung cancer bone metastasis and endothelin-1 (ET-1) injections once daily on postoperative days 16-18, with validation through behavioral and electrophysiological assessments. Spinal EAAT1, EAAT2 and connexin 43 (Cx43) were investigated. Mice were administered intrathecal ceftriaxone (EAAT2 activator), Gap26 (gap junction blocker), or control agents.

Results: The BTcP model showed reduced pain thresholds and function, accompanied by decreased EAAT1/EAAT2 and increased phosphorylated C×43 (p-Cx43) in spinal astrocytes. Ceftriaxone reversed pain hypersensitivity, upregulated EAAT2, and reduced p-Cx43 without affecting EAAT1/total Cx43. Gap26 increased EAAT1/EAAT2, decreased Cx43/p-Cx43, and alleviated pain behaviors.

Conclusion: This optimized ET-1 model provides a robust platform for BTcP research. Spinal EAATs, downregulation and C×43 activation, contribute to BTcP pathogenesis, and both are potential therapeutic targets of BTcP.

Purpose: The objective of this study is to investigate the mechanism of cuproptosis regulation in TMZ resistance in GBM, and provide an important theoretical basis for the rational design of combination therapy to block TMZ resistance.

Methods: The experimental participants were divided into four groups, including a control group (Control), a Control + CU-ES group, a TMZ group, and a TMZ + copper ion carrier (TMZ + CU-ES) group. TMZ-resistant U87 MG cell lines (U87 MG/TR) were established using a concentration gradient method. Cell proliferation rates were assessed using the CCK8 assay, apoptosis was analyzed via flow cytometry, and gene and protein expression levels of caspase-3 and caspase-9 were detected by using qRT-PCR and Western Blot. Differences in cell proliferation, apoptosis, and apoptosis-related molecule expression were compared across groups.

Results: The U87 MG/TR-resistant strain was established (IC50 =141.5 μM). Compared with the Control group, TMZ group showed a decrease in the cell proliferation rate but an increase in the apoptosis rate (p < 0.05). The TMZ + CU-ES group exhibited a further significant reduction in the cell proliferation rate and a significant increase in the apoptosis rate. The expression of caspase-3 and caspase-9 in the TMZ + CU-ES group was significantly higher than that in the TMZ group.

Conclusion: TMZ resistance in glioma cells was affectively reversed by the cuproptosis pathway, a mechanism likely involving the activation of the intrinsic apoptotic pathway. This finding offered a novel strategy for overcoming TMZ resistance.

Background: Epilepsy remains a major neurological disorder with high rates of drug resistance and cognitive decline. Repurposing neuroprotective drugs offers a promising approach. Metformin, a widely used antidiabetic agent, has shown anticonvulsant effects, yet its impact on nitric oxide synthase (NOS) isoforms in distinct brain regions remains unclear.

Methods: Adult male Wistar rats were allocated into control, pentylenetetrazole (PTZ), or metformin+PTZ groups. Metformin (200 mg/kg, i.p.) was administered for 7 days before induction of acute PTZ seizures (45 mg/kg, i.p.). Seizure severity and latency were assessed using Racine's scale, and cognition was evaluated by the passive avoidance test (PAT). Nitric oxide (NO) and the expression of its synthesizing enzymes, inducible (iNOS), neuronal (nNOS), and endothelial (eNOS), were quantified in the cortex and hippocampus via enzyme-linked immunosorbent assay (ELISA). In silico analyses included target prediction and molecular docking to assess metformin - NOS interactions.

Results: Metformin significantly reduced seizure severity, prolonged latency to the first myoclonic jerk, and prevented PTZ-induced memory impairment (all p < 0.001). These behavioral effects were accompanied by reductions in cortical and hippocampal nNOS and iNOS expression, decreased cortical eNOS levels, and lower NO accumulation. TargetNet predicted NOS isoforms among potential metformin targets, and docking indicated moderate binding affinity (-5.2 to -5.9 kcal/mol).

Conclusion: Metformin exerted seizure-suppressing and cognition-preserving effects in an acute PTZ model, associated with reductions in NOS isoform expression and NO levels, suggesting altered NOS/NO signaling and supporting its potential as an adjunctive candidate for mitigating seizure-related neuronal dysfunction.