Current neurovascular research最新文献

Background: Increasing evidence of circadian biology may influence the physiopathologic mechanism, progression, and recovery of stroke. However, few data have shown about circadian rhythm on futile recanalization (FR) in patients treated with endovascular treatment (EVT).

Methods: From 2017 to 2021, an observational cohort of acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) underwent EVT was conducted. FR was defined as the failure to achieve functional independence in patients at 90 days after EVT, although the occluded vessels reached a recanalization. The effect of circadian rhythm on FR was investigated using the logistic regression model.

Results: Of 783 patients, there were 149 patients who had stroke onset between 23:00-6:59, 318 patients between 7:00-14:59, and 316 patients between 15:00-22:59. Patients suffered from stroke during 15:00-22:59 had shorter OTP (p =0.001) time, shorter OTR (p<0.001) time, higher rate of intravenous thrombolysis (p =0.001) than groups of other time intervals. The rate of FR post-EVT in patients who had a stroke between 15:00-22:59 was significantly higher than in those with stroke onset between 23:00-6:59 (p =0.017). After adjusting for confounding factors, the time of stroke occurring during 15:00-22:59 (adjusted OR [aOR], 1.652; 95%CI, 1.024-2.666, p =0.04) was an independent predictor of FR.

Conclusion: Circadian rhythm can directly or indirectly affect the occurrence, development, and prognosis of AIS. More studies may be needed in the future to validate the results of our study and to explore the potential mechanisms behind the effects of circadian rhythms on FR.

Introduction: 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).

Methods: 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.

Results: 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.

Discussion: 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.

Conclusion: 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.

Objective: The concept of "time is brain" is crucial for the reperfusion therapy of ischemic stroke. However, the Infarct Growth Rate (IGR) varies among individuals, which is regarded as a more powerful factor than the time when determining infarct volume and its association with clinical outcomes. For stroke patients with a similar infarct volume, a longer time from stroke Onset to Imaging (OTI) correlates with a lower IGR, which may indicate a better prognosis. This study aimed to compare the prognoses of patients with anterior circulation stroke who received Endovascular Treatment (EVT), specifically comparing early EVT vs. late EVT.

Methods: We analyzed 255 patients with acute anterior circulation stroke due to large vessel occlusion and who have successfully undergone recanalization after EVT. All patients were divided into the late (OTI≥6 hours) and early (<6 hours) time window groups and compared. The primary outcome was moderate functional prognosis, defined as a modified Rankin Scale (mRS) ≤3 at 90 days. The secondary outcome was No Significant Infarct Expansion (NSIE), defined as a reduction of less than 2 points on the Alberta Stroke Program Early CT Score (ASPECTS).

Results: In the moderate to large infarct subgroup, the late time window EVT was independently associated with a higher rate of moderate functional outcome (P =0.007) and NSIE (P =0.001); mediation analysis showed that NSIE partially mediated the effects of the late time window EVT on moderate functional outcome (coefficient: 0.112, 95% CI: 0.051 to 0.239, P =0.011); however, these associations were not consistent in the small infarct group.

Conclusion: For anterior circulation stroke patients who received EVT according to current guidelines, those with moderate to large infarct volume and having a longer OTI had better clinical outcomes than those who had a shorter OTI and were more suitable for EVT.

Introduction: The endothelial barrier is composed of brain microvascular endothelial cells (BMECs) and tight junction (TJ) proteins. Musk is a valuable ingredient in Traditional Chinese Medicine (TCM). It is used in the treatment of stroke because of its ability to induce resuscitation. The core component of musk is muscone. Previous studies have evidenced that muscone may be involved in the treatment of ischemic stroke (IS), but the underlying mechanism is still unclear. The main objective of this study was to explore the protective effect of muscone on OGD/R-induced endothelial barrier disruption and determine its underlying mechanism.

Methods: OGD/R-induced damage to BMECs was assessed using the MTT and LDH assays. The apoptosis level in BMECs was determined using western blot and Hoechst staining. Western blot, immunofluorescence, and phalloidin staining were used to assess the expressions of TJ proteins and pathway proteins expression. A monolayer cell barrier was constructed using BMECs in vitro, and the permeability of the barrier was assessed by TEER as well as the transmissivity of sodium fluorescein. Molecular docking, DARTS, and CETSA were used to verify the regulatory effect of muscone on the pathway.

Results: Muscone reduced OGD/R-induced apoptosis of BMEC cells, inhibited the degradation of TJ proteins, promoted the coherent expression of ZO-1 on the membrane, and restored TEER. Mechanistic studies showed that H-89 reversed the promoting effects of muscone on pathway proteins and promoted the disassembly of the actin cytoskeleton, which, in turn, promotes BMEC apoptosis and TJ protein degradation, ultimately disrupting the endothelial barrier.

Discussion: The inhibition of BMEC apoptosis and improvement of endothelial barrier damage by muscone may be an important mechanism for treating ischemic stroke.

Conclusion: We demonstrated that muscone could reduce OGD/R-induced hyperpermeability of the brain endothelial barrier by activating the PKA/RHOA/MLC pathway.

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.

Background and purpose: 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.

Objective: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Multiple sclerosis (MS) is a progressive autoimmune condition that primarily affects young people and is characterized by demyelination and neurodegeneration of the central nervous system (CNS). This in-depth review explores the complex involvement of oligodendrocytes, the primary myelin- producing cells in the CNS, in the pathophysiology of MS. It discusses the biochemical processes and signalling pathways required for oligodendrocytes to function and remain alive, as well as how they might fail and cause demyelination to occur. We investigate developing therapeutic options that target remyelination, a fundamental component of MS treatment. Remyelination approaches promote the survival and differentiation of oligodendrocyte precursor cells (OPCs), restoring myelin sheaths. This improves nerve fibre function and may prevent MS from worsening. We examine crucial parameters influencing remyelination success, such as OPC density, ageing, and signalling pathway regulation (e.g., Retinoid X receptor, LINGO-1, Notch). The review also examines existing neuroprotective and antiinflammatory medications being studied to see if they can assist oligodendrocytes in surviving and reducing the severity of MS symptoms. The review focuses on medicines that target the myelin metabolism in oligodendrocytes. Altering oligodendrocyte metabolism has been linked to reversing demyelination and improving MS patient outcomes through various mechanisms. We also explore potential breakthroughs, including innovative antisense technologies, deep brain stimulation, and the impact of gut health and exercise on MS development. The article discusses the possibility of personalized medicine in MS therapy, emphasizing the importance of specific medicines based on individual molecular profiles. The study emphasizes the need for reliable biomarkers and improved imaging tools for monitoring disease progression and therapy response. Finally, this review focuses on the importance of oligodendrocytes in MS and the potential for remyelination therapy. It also underlines the importance of continued research to develop more effective treatment regimens, taking into account the complexities of MS pathology and the different factors that influence disease progression and treatment.

Background: Ischemic stroke due to Large Vessel Occlusion (LVO) represents a critical and time-sensitive neurological emergency. Advancements in imaging technology and endovascular therapies have transformed the management of LVO. Nonetheless, thrombectomy failure diminishes the chances of patients achieving a favorable clinical outcome.

Objective: We aimed to determine the factors influencing recanalization failure in order to optimize thrombectomy therapy along with enhancing patient outcomes.

Methods: A retrospective analysis was performed employing consecutive LVO patients who underwent Endovascular Thrombectomy (EVT) in a tertiary comprehensive stroke center between January 2020 and June 2024. Recanalization failure (mTICI 0-2a) following thrombectomy was assessed using the Kolmogorov-Smirnov test, χ² test, Fisher's exact test, and multivariable logistic regression to identify the related factors.

Results: A total of 82 EVT patients were analyzed. The mean age was 58.20 years and 70.73% of the patients were male. The rate of recanalization failure was 61%. Multivariable logistic regression analysis with age-sex adjusted factors has revealed hypertension [aOR: 5.31 (95% CI: 1.23-22.77); p =0.025] and no IVT [aOR: 2.75 (95% CI: 1.06-7.14); p =0.037] to be independent predictors of recanalization failure in this study.

Conclusion: Hypertension and the absence of prior intravenous thrombolysis have been found to be significant contributing factors to the high rate of thrombectomy failure in large-vessel occlusion.