Current neurovascular research最新文献

The close connection between the brain microvascular endothelial cells (BMECs) that are enclosed within this barrier is the result of an intracellular junction, which is responsible for the constricted connection. The regulation and control of drug delivery systems both require nanoparticles, which are extremely small particles made up of a variety of materials, including polymers, metals, and other chemicals. Nanoparticles are a crucial component of the regulation and control of drug delivery systems. There is a possibility that nanomaterials composed of inorganic chemicals, such as gold nanoparticles, could be utilized in the treatment of neurodegenerative illnesses like Parkinson's disease. In addition to this, they are used as nano-carriers for the aim of distributing drugs to the region of the brain that is being targeted. There are a number of advantages that are easily apparent when compared to other methods of administering drugs for neurological diseases. The current review demonstrates both the advantages and disadvantages of utilizing a wide variety of nanomaterials for brain delivery, as well as the potential impact that this will have in the future on the safety and effectiveness of patient care.

Background: Aloe-emodin (AE), a monomer derived from traditional Chinese medicine, has demonstrated remarkable efficacy in the clinical management of cognitive disorders. Ferroptosis (FPT), a specialized form of programmed cell death, plays a critical role in the pathological progression of various cognitive diseases.

Methods: This study explored the therapeutic potential of AE in a rat model of Wilson's disease cognitive impairments (WDCI) and examined whether these effects are mediated through the silencing information regulator 1 (SIRT1)-regulated FPT signaling pathway. Employing techniques, such as the Morris water maze (MWM), Hematoxylin & eosin (H&E) staining, Transmission electron microscopy (TEM), Immunofluorescence (IF), assessments of oxidative stress markers, and measurements of FPT-related protein levels, we evaluated the extent of SIRT1-mediated FPT and the therapeutic efficacy of AE.

Results: The findings from the WD copper-loaded rat model experiments revealed that MWM, H&E, TEM, and IF outcomes indicated AE's potential to promote the restoration of learning and memory functions, ameliorate hippocampal neuronal morphological damage, and preserve cell membrane integrity. Results from western blot (WB) and ELISA analyses demonstrated that AE markedly upregulated the expression of SIRT1, nuclear factor erythroid-2-related factor 2 (Nrf2), solute carrier family 7 member 11 (SCL7A11), and glutathione peroxidase 4 (GPX4) proteins while simultaneously reversing the expression of oxidative stress markers such as malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD), and reactive oxygen species (ROS). Consequently, we posit that AE may attenuate WD copper-loaded rat model hippocampal neuronal FPT by activating the SIRT1-mediated signaling pathway.

Conclusion: These findings suggested that AE mitigates WD copper-loaded rat model hippocampal neuronal damage through the activation of SIRT1-mediated FPT, thereby presenting a valuable candidate Chinese herbal monomer for the clinical treatment of WDCI.

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: This study aimed to explore Malignant Brain Edema (MBE) and associated factors in patients with Large Hemispheric Infarction (LHI) following early reperfusion therapy.

Methods: We consecutively and retrospectively enrolled a cohort of 114 LHI patients who had received early reperfusion therapy, including Intravenous Thrombolysis (IVT) or Endovascular Therapy (EVT) at the hyperacute stage of stroke between January 2009 and December 2018. MBE was defined as a midline shift ≥5 mm, accompanied by signs of herniation. Multivariate logistic analyses were conducted to identify independent factors associated with MBE in LHI patients following early reperfusion therapy.

Results: Among the enrolled patients, 69 (60.53%) were treated with IVT alone and 45 (39.47%) with EVT. Successful recanalization was achieved in 56 (49.12%) patients, while complete recanalization was achieved in 38 (33.33%) patients. After early reperfusion therapy, 50 (43.86%) developed MBE in LHI patients. The MBE group showed higher rates of in-hospital death (54% vs. 4.69%), 3-month mortality (64% vs. 10.94%), and 3-month unfavorable outcomes (90% vs. 64.06%) (all p<0.01). Neither different reperfusion therapy (EVT vs. IVT alone) nor different recanalization status (complete recanalization or not) was independently associated with the development of MBE in LHI patients following reperfusion therapy in multivariate analyses. MBE was independently associated with age [Odds Ratio (OR) 0.953, 95% confidence interval (CI) 0.910-0.999, p =0.044], right hemisphere stroke (OR 4.051, 95% CI 1.035-15.860, p =0.045), previous ischemic stroke or TIA (OR 0.090, 95% CI 0.014-0.571, p =0.011), and hypodensity >1/3 MCA territory (OR 8.071, 95% CI 1.878-34.693, p =0.005). Meanwhile, patients with lower baseline Alberta Stroke Program Early CT Score (ASPECTS) had a trend of higher incidence of MBE following reperfusion therapy (OR 0.710, 95% CI 0.483-1.043, p =0.081).

Conclusion: MBE occurred in nearly one-half of LHI patients following early reperfusion therapy and was related to poor outcomes. An increased risk of MBE was found to be associated with younger age, right hemisphere stroke, absence of a history of ischemic stroke or TIA, and hypodensity >1/3 MCA region on baseline CT images.

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: Neuroinflammation is recognized as one of the pathogenic mechanisms underlying sepsis-associated encephalopathy (SAE). As the most commonly used anesthetic agent in the perioperative period, propofol has been demonstrated to exhibit neuroprotective and anti-inflammatory effects. This study aimed to investigate whether propofol could mitigate lipopolysaccharide (LPS)-mediated neuroinflammation and to explore the potential mechanisms.

Methods: hCMEC/D3 cells were treated with propofol, followed by LPS exposure. Western blot, ELISA, and RT-qPCR were used to assess the expression (both protein and mRNA levels) of potential pathway participants. Intracellular Fe²⁺ levels were determined using an Iron Assay Kit. In addition, an in vitro blood-brain barrier (BBB) model was constructed by co-culturing hCMEC/D3 cells and human astrocytes, and BBB permeability was assessed by measuring trans-endothelial electrical resistance (TEER).

Results: LPS (50 μg/mL, 1 h) significantly increased the secretion of TNF-α and IL-1β, induced intracellular Fe²⁺ accumulation, and upregulated the expression of 4-HNE, H3K18la, pan-Kla, and LDHA, while decreasing the expression of ZO-1, Claudin-5, and Occludin in hCMEC/D3 cells. More importantly, propofol (25 μM, 2 h) alleviated the aforementioned effects of LPS on hCMEC/D3 cells. Furthermore, we observed significant LPS-induced TEER reduction in the in vitro BBB model, and this effect was attenuated by propofol pretreatment.

Discussion: The protective effect of propofol on hCMEC/D3 cells' ferroptosis and LDHAlactylation induced by LPS may be an important mechanism for neuroinflammation.

Conclusion: Propofol inhibits LPS-induced lactylation, ferroptosis, and release of inflammatory cytokines in hCMEC/D3 cells by downregulating the expression of LDHA.

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.

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.