Current Neurovascular Research - Volume 22, Issue 1, 2025

Sepsis-associated encephalopathy (SAE) is the most severe complication of sepsis. Ubiquitin-specific protease 8 (USP8) could improve cognitive and motor disorders in SAE.

This study explored the mechanism of USP8 in SAE mice to provide new therapeutic targets for SAE.

C57BL/6 mice were selected to establish SAE models by caecal ligation and puncture (CLP) and injected with lentivirus overexpressing USP8 one week before SAE modeling. Mouse weight changes were monitored, cognitive and learning abilities were tested by the Morris water maze test, behaviors were evaluated by open-field tests, and pathological changes in brain tissue were analyzed by H&E staining. Levels of USP8, TNF-α, IL-1β, IL-6, and IL-10, and SOD, GSH-Px activities, and MDA levels were detected by Western blot, ELISA, and kits. Co-immunoprecipitation assay verified the interaction between USP8 and SIRT1 and SIRT1 ubiquitination level.

In CLP mice, the body weight, cognitive function, and learning ability were decreased, along with motor disorder, abnormal morphological structure of neurons, and obvious inflammatory infiltration. USP8 protein in brain tissue was decreased, the levels of TNF-α, IL-1β, and IL-6 were increased, IL-10 was decreased, SOD and GSH-Px activities were decreased, and MDA level was increased. USP8 treatment improved cognitive dysfunction and inhibited inflammation and oxidative stress in CLP mice. USP8 promoted SIRT1 expression by direct deubiquitination. SIRT1 knockdown partially reversed the regulation of USP8 on SAE mice.

USP8 can directly deubiquitinate SIRT1 and inhibit inflammatory reactions and oxidative stress, thus improving cognitive dysfunction in SAE mice.

The relationships between serum albumin, albumin-globulin (A/G) ratio, globulin and atherosclerosis in acute ischemic stroke (AIS) remain uncertain. We investigated the associations between serum albumin, A/G ratio, globulin levels and carotid atherosclerosis in patients with AIS.

A total of 1,339 AIS patients were enrolled. Admission A/G ratio was divided into quartiles, and serum albumin and globulin levels were also categorized. Carotid atherosclerosis was detected through the assessment of common carotid artery intima-media thickness (cIMT), and abnormal cIMT was characterized by mean and maximum cIMT values of ≥1 mm. We evaluated the relationships between A/G ratio, albumin, globulin and abnormal cIMT, using multivariable logistic regression models.

In the multivariable-adjusted analysis, the highest A/G ratio quartile (Q4) was linked to a 59% decreased risk of abnormal mean cIMT (OR 0.41; 95% CI 0.29-0.60) and a 58% decreased risk of abnormal maximum cIMT (OR 0.42; 95% CI 0.30-0.60) when compared to the lowest quartile (Q1), respectively. Moreover, decreased albumin and elevated globulin levels were also associated with abnormal mean cIMT and maximum cIMT. In addition, the A/G ratio provided supplementary predictive capability beyond the already established risk factors, and the C-statistic of the A/G ratio for abnormal cIMT is larger than globulin (P <0.01).

Decreased serum A/G ratio, albumin and elevated serum globulin were independently associated with abnormal cIMT in AIS patients. Moreover, the A/G ratio appeared to be a better predictor of abnormal cIMT.

Mechanical Thrombectomy (MT) is the recommended treatment for patients with an acute ischemic stroke (AIS) due to large vessel occlusion (LVO) within 6 h after onset. However, the poor prognosis for patients with an acute great vascular occlusive stroke after an MT, which is a common occurrence, can be attributed to an absence of appropriate postoperative monitoring. Transcranial Doppler (TCD) ultrasound and Quantitative Electroencephalography (QEEG) offer the advantages of rapid, convenient, and bedside examinations compared to conventional imaging techniques.

In the current study, we analyzed the predictive performance of clinical factors, TCD ultrasound, and QEEG for the prognosis of patients with an AIS due to LVO 90 days after hospital discharge.

Patients who achieved revascularization following an MT that was performed within 6 h after the onset of AIS due to LVO were included. We used the data to build four predictive models of prognosis and compared the predictive performance measured by the area under the curve, sensitivity, and specificity.

Seventy-four patients were included in the study, among whom 47 had a poor prognosis (63.5%) at the time of hospital discharge, and 45 had a poor prognosis (60.8%) 90 d after hospital discharge. Independent predictors of poor prognosis 90 d after hospital discharge included the following: age, National Institute of Health stroke scale (NIHSS) score at the time of hospital admission, pulsatility index (PI) on the affected/healthy side, and relative alpha power (RAP). The area under the receiver operating characteristic curve (AUC) was highest (0.831) among the 4 models when age was combined with NIHSS score at the time of hospital admission, TCD parameters (diastolic velocity [VD] on the affected side and PI on the affected/healthy side), and a QEEG parameter (e.g., RAP) for prognostic prediction. However, the AUC for the 4 predictive models did not differ significantly (p > 0.05).

Age, the NIHSS score at the time of hospital admission, TCD parameters, and a QEEG parameter were independent predictors of prognosis 90 d after discharge in patients undergoing MT for AIS due to LVO in the anterior circulation. The model combining the above four parameters may be helpful for prognostic prediction in such patients.

Headaches affect up to 95% of individuals during their lifetime and are a major global cause of disability. Intracranial Aneurysm (IA) is a cerebrovascular disorder affecting approximately 3.2% of the general population. Observational studies have suggested an association between headaches and IA, but the causal relationship remains unclear. This Mendelian Randomization (MR) analysis aims to elucidate the causal relationship between headaches and IA.

A two-sample bidirectional Mendelian Randomization (MR) analysis was performed using publicly available Genome-Wide Association Study (GWAS) data to assess the causal relationships between IA and four headache subtypes, namely, Chronic Headache (CH), Tension-Type Headache (TTH), Migraine Without Aura (MO), and Migraine With Aura (MA). The inverse variance weighted method was employed as the primary method, with sensitivity analyses conducted to evaluate the robustness of the results. Mediation analysis was performed to investigate the potential mediating role of hypertension.

The MR analysis revealed that MO was associated with an increased risk of aneurysmal Subarachnoid Hemorrhage (aSAH) (Odds Ratio [OR] = 1.422, 95% Confidence Interval [CI]: 1.054–1.918, and P = 0.021), while MA (OR = 1.527, 95% CI: 1.115–2.091, and P = 0.008) was associated with an elevated risk of unruptured IA (uIA). Mediation analysis indicated that hypertension did not significantly mediate these associations.

This study highlights the potential role of MO in aSAH and MA in uIA, where hypertension does not serve as a significant mediator. Further research is necessary to investigate the underlying mechanisms, which may offer valuable insights into the prevention and management of IA.

Bidirectional MR analysis of four headache subtypes and IA provides evidence that MO is associated with an increased risk of aSAH, while MA is linked to a higher risk of uIA. These findings contribute to a better understanding of the complex relationship between headaches and IA.

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.

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.

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; Ptrend =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).

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.

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

Excellent reperfusion following mechanical thrombectomy (MT) is strongly associated with favorable clinical outcomes in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). This study aims to investigate the association between the cerebral blood volume (CBV) index-a surrogate marker of collateral status-and the likelihood of achieving excellent reperfusion after MT in AIS-LVO patients.

A retrospective analysis was conducted on a consecutive series of anterior circulation AIS-LVO patients undergoing MT. CBV index was calculated using RAPID software as the ratio of mean CBV in the penumbral region (Tmax > 6 seconds) to that in the unaffected brain region (Tmax≤4 seconds). The primary outcome was excellent reperfusion, defined as an expanded Thrombolysis in Cerebral Infarction (eTICI) score of 2c/3.

Of the 245 patients (54.70% male, median age 71 years), 152 (62.04%) achieved excellent reperfusion. ROC analysis identified a CBV index ≥0.6 as the optimal cutoff for predicting excellent reperfusion (AUC=0.743). Multivariable logistic regression showed a positive association between the CBV index and excellent reperfusion (adjusted OR = 1.221 per 0.1-point increase, 95% CI: 1.028-1.449, p=0.023). Patients with a favorable CBV index (≥0.6) were significantly more likely to achieve excellent reperfusion (adjusted OR = 2.785, 95% CI: 1.258-6.164, p = 0.012).

These findings suggest that the CBV index is an independent predictor of excellent reperfusion after MT in AIS-LVO patients. This association may reflect the importance of tissue-level collateral perfusion in achieving successful reperfusion. Limitations include the single-center, retrospective design and the potential for selection bias.

The CBV index is positively associated with excellent reperfusion in AIS-LVO patients undergoing MT. Further prospective studies are warranted to validate these findings and explore the underlying mechanisms.

Hyperdense Middle Cerebral Artery (HMCAS) is one of the early CT signs of acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). Whether HMCAS is an accurate predictor of functional outcomes in LVO-AIS patients still needs to be further studied. This study aimed to evaluate the prognostic value of the HMCAS for functional outcomes in patients with LVO-AIS receiving emergency endovascular treatment (EVT), with or without prior intravenous thrombolysis (IVT).

The clinical and imaging data in LVO-AIS patients who underwent EVT with or without IVT were retrospectively analyzed. The patients were divided into HMCAS+ group and HMCAS- group according to the presence or absence of HMCAS on initial CT. The endpoint was the 90-day Modified Rankin Scale (mRS), and multivariate logistic ordinal regression was used to determine the association between the presence of HMCAS and 90-day mRS.

A total of 173 LVO-AIS patients were recruited for this study, with 69 (39.88%) in the HMCAS+ group and 104 (60.12%) in the HMCAS− group. The mean age of the participants was 68.98±13.529 years, with 89 (49.71%) being male and 67 (38.73%) receiving IVT. Multivariate logistic regression of the presence of HMCAS (OR, 1.240 95% CI, 0.693-2.219 P =0.511) was not significantly associated with the 90-day mRS score.

The HMCAS typically occurs in cases with red blood cell (RBC)-dominant thrombi or thrombi exhibiting a balanced composition of RBCs and fibrin. However, in patients undergoing EVT, thrombus removal is achieved through physical extraction, diminishing the influence of thrombus composition on procedural success.

HMCAS may not be a predictor of 90-day mRS in LVO-AIS patients undergoing EVT. However HMCAS+ group patients had higher stroke severity before IVT and EVT. In the era of EVT, the factors affecting the prognosis of LVO-AIS may be different from those of the past.