Investigation on acceptor-donor co-doped SnO2 nanoparticles enriched with oxygen vacancies: a capacitive humidity sensor for respiration detection.

In this work, we develop a novel capacitive humidity sensor based on Al-Si acceptor-donor co-doped SnO2 for real-time monitoring of ambient humidity and human respiration. XRD measurements reveal that all samples exhibit a tetragonal rutile phase and the crystallite size of SnO2 decreases with increasing Al-Si content. The high intensity of the Raman peak at 762 cm-1 confirms the presence of bridging mode oxygen vacancies in (Al + Si)0.02Sn0.98O2. The EPR results show that the amount of singly ionized oxygen vacancies increases after the introduction of Al-Si. Both types and amounts of oxygen vacancy defects are particularly sensitive to the adsorption of water molecules. Moreover, according to DFT calculations, the contribution of the Si 3s orbital and Al 3s orbital to the band edge verifies the formation of acceptor-donor complexes in Al-Si co-doped SnO2. The humidity sensing results reveal that the (Al + Si)0.02Sn0.98O2 humidity sensor shows high sensitivity (S = 839), low hysteresis (1.94%) and fast response/recovery times (25 s/5 s). The respiratory intervals during shallow, medium and deep breathing states of (Al + Si)0.02Sn0.98O2 were measured at 2.8 s, 3.8 s and 4.5 s, respectively. The chemical mechanism for the enhancement of humidity sensing performance corresponding to the oxygen vacancy defects induced by Al-Si interplay is proposed.

Modulation of NLRP3 inflammasome-related-inflammation via RIPK1/RIPK3-DRP1 or HIF-1α signaling by phenothiazine in hypothermic and normothermic neuroprotection after acute ischemic stroke.

BACKGROUND: Inflammation and subsequent mitochondrial dysfunction and cell death worsen outcomes after revascularization in ischemic stroke. Receptor-interacting protein kinase 1 (RIPK1) activated dynamin-related protein 1 (DRP1) in a NLRPyrin domain containing 3 (NLRP3) inflammasome-dependent fashion and Hypoxia-Inducible Factor (HIF)-1α play key roles in the process. This study determined how phenothiazine drugs (chlorpromazine and promethazine (C + P)) with the hypothermic and normothermic modality impacts the RIPK1/RIPK3-DRP1 and HIF-1α pathways in providing neuroprotection. METHODS: A total of 150 adult male Sprague-Dawley rats were subjected to 2 h middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion. 8 mg/kg of C + P was administered at onset of reperfusion. Infarct volumes, mRNA and protein expressions of HIF-1α, RIPK1, RIPK3, DRP-1, NLRP3-inflammation and cytochrome c-apoptosis were assessed. Apoptotic cell death, infiltration of neutrophils and macrophages, and mitochondrial function were evaluated. Interaction between RIPK1/RIPK3 and HIF-1α/NLRP3 were determined. In SH-SY5Y cells subjected to oxygen/glucose deprivation (OGD), the normothermic effect of C + P on inflammation and apoptosis were examined. RESULTS: C + P significantly reduced infarct volumes, mitochondrial dysfunction (ATP and ROS concentration, citrate synthase and ATPase activity), inflammation and apoptosis with and without induced hypothermia. Overexpression of RIPK1, RIPK3, DRP-1, NLRP3-inflammasome and cytochrome c-apoptosis were all significantly reduced by C + P at 33 °C and the RIPK1 inhibitor (Nec1s), suggesting hypothermic effect of C + P via RIPK1/RIPK3-DRP1pathway. When body temperature was maintained at 37 °C, C + P and HIF-1α inhibitor (YC-1) reduced HIF-1α expression, leading to reduction in mitochondrial dysfunction, NLRP3 inflammasome and cytochrome c-apoptosis, as well as the interaction of HIF-1α and NLRP3. These were also evidenced in vitro, indicating a normothermic effect of C + P via HIF-1α. CONCLUSION: Hypothermic and normothermic neuroprotection of C + P involve different pathways. The normothermic effect was mediated by HIF-1α, while hypothermic effect was via RIPK1/RIPK3-DRP1 signaling. This provides a theoretical basis for future precise exploration of hypothermic and normothermic neuroprotection.

The possible causal relationship between COVID-19 and imaging markers of cerebral small vessel disease: a Mendelian randomization study.

OBJECTIVES: Observational studies have suggested that SARS-CoV-2 infection may increase the burden of cerebral small vessel disease (CSVD). This study aims to explore the causal correlation between COVID-19 and the imaging markers of CSVD using Mendelian randomization (MR) methods. METHODS: Summary-level genome-wide association study (GWAS) statistics for COVID-19 susceptibility, hospitalization, and severity were utilized as proxies for exposure. Large-scale meta-analysis GWAS data on three neuroimaging markers of white matter hyperintensity, lacunar stroke, and brain microbleeds, were employed as outcomes. Our primary MR analysis employed the inverse variance weighted (IVW) approach, supplemented by MR-Egger, weighted median, and MR-PRESSO methods. We also conducted multivariable MR analysis to address confounding bias and validate the robustness of the established causal estimates. Comprehensive sensitivity analyses included Cochran's Q test, Egger-intercept analysis, MR-PRESSO, and leave-one-out analysis. RESULTS: The MR analysis revealed a significant causal correlation between the severity of COVID-19 and an increased risk of lacunar stroke, as demonstrated by the IVW method (ORivw = 1.08, 95% CI: 1.03-1.16, pivw = 0.005, FDR = 0.047). Nevertheless, no causal correlations were observed between COVID-19 susceptibility or hospitalization and any CSVD imaging markers. The robustness and stability of these findings were further confirmed by multivariable MR analysis and comprehensive sensitivity analyses. DISCUSSION: This study provides compelling evidence of a potential causal effect of severe COVID-19 on the incidence of lacunar stroke, which may bring fresh insights into the understanding of the comorbidity between COVID-19 and CSVD.

A Comprehensive Prediction Model for Futile Recanalization in AIS Patients Post-Endovascular Therapy: Integrating Clinical, Imaging, and No-Reflow Biomarkers.

Our study aimed to construct a predictive model for identifying instances of futile recanalization in patients with anterior circulation occlusion acute ischemic stroke (AIS) who achieved complete reperfusion following endovascular therapy. We included 173 AIS patients who attained complete reperfusion, as indicated by a Modified Thrombolysis in Cerebral Infarction (mTICI) scale score of 3. Our approach involved a thorough analysis of clinical factors, imaging biomarkers, and potential no-reflow biomarkers through both univariate and multivariate analyses to identify predictors of futile recanalization. The comprehensive model includes clinical factors such as age, presence of diabetes, admission NIHSS score, and the number of stent retriever passes; imaging biomarkers like poor collaterals; and potential no-reflow biomarkers, notably disrupted blood-brain barrier (OR 4.321, 95% CI 1.794-10.405; p = 0.001), neutrophil-to-lymphocyte ratio (NLR; OR 1.095, 95% CI 1.009-1.188; p = 0.030), and D-dimer (OR 1.134, 95% CI 1.017-1.266; p = 0.024). The model demonstrated high predictive accuracy, with a C-index of 0.901 (95% CI 0.855-0.947) and 0.911 (95% CI 0.863-0.954) in the original and bootstrapping validation samples, respectively. Notably, the comprehensive model showed significantly improved predictive performance over models that did not include no-reflow biomarkers, evidenced by an integrated discrimination improvement of 8.86% (95% CI 4.34%-13.39%; p < 0.001) and a categorized reclassification improvement of 18.38% (95% CI 3.53%-33.23%; p = 0.015). This model, which leverages the potential of no-reflow biomarkers, could be especially beneficial in healthcare settings with limited resources. It provides a valuable tool for predicting futile recanalization, thereby informing clinical decision-making. Future research could explore further refinements to this model and its application in diverse clinical settings.

Impacts of futile reperfusion and reperfusion injury in acute ischemic stroke.

Acute ischemic stroke (AIS) remains to be a challenging cerebrovascular disease. The mainstay of AIS management is endovascular reperfusion therapy, including thrombectomy and thrombolysis. However, ineffective (futile) reperfusion (FR) or reperfusion injury (RI) can be seen in a significant number of patients undergoing reperfusion strategy. In this article, we discuss two clinically relevant concepts known as "time window" and "tissue window" that can impact the clinical outcome of reperfusion therapy. We also explore patient risk factors, leading to FR and RI as well as an emerging concept of "no-reflow phenomenon" seen in ineffective reperfusion. These fundamental concepts provide insight into the clinical management of AIS patients and provide references for future research.

A narrative review of potential neural repair poststroke: Decoction of Chinese angelica and peony in regulating microglia polarization through the neurosteroid pathway.

Ischemic stroke is a major global health crisis, characterized by high morbidity and mortality rates. Although there have been significant advancements in treating the acute phase of this condition, there remains a pressing need for effective treatments that can facilitate the recovery of neurological functions. Danggui-Shaoyao-San (DSS), also known as the Decoction of Chinese Angelica and Peony, is a traditional Chinese herbal formula. It has demonstrated promising results in the regulation of microglial polarization and modulation of neurosteroid receptor expression, which may make it a potent strategy for promoting the recovery of neurological functions. Microglia, which plays a crucial role in neuroplasticity and functional reconstruction poststroke, is regulated by neurosteroids. This review posits that DSS could facilitate the recovery of neuronal function poststroke by influencing microglial polarization through the neurosteroid receptor pathway. We will further discuss the potential mechanisms by which DSS could enhance neural function in stroke, including the regulation of microglial activation, neurosteroid regulation, and other potential mechanisms.

Efficacy and Safety of Long-Term Dual Antiplatelet Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is a standard therapy in patients with ischemic vascular diseases (IVD) including coronary artery, cerebrovascular and peripheral arterial diseases, although the optimal duration of this treatment is still debated. Previous meta-analyses reported conflicting results about the effects of long-term and short-term as well as non-DAPT use in various clinical settings. Herein, we conducted a comprehensive meta-analysis to assess the efficacy and safety of different durations of DAPT. METHODS: We reviewed relevant articles and references from database, which were published prior to April 2023. Data from prospective studies were processed using RevMan5.0 software, provided by Cochrane Collaboration and transformed using relevant formulas. The inclusion criteria involved randomization to long-term versus short-term or no DAPT; the endpoints included at least one of total or cardiovascular (CV) mortalities, IVD recurrence, and bleeding. RESULTS: A total of 34 randomized studies involving 141 455 patients were finally included. In comparison with no or short-term DAPT, long-term DAPT reduced MI and stroke, but did not reduce the total and CV mortalities. Meanwhile, bleeding events were increased, even though intracranial and fatal bleedings were not affected. Besides, the reduction of MI and stroke recurrence showed no statistical significance between long-term and short-term DAPT groups. CONCLUSION: Long-term DAPT may not reduce the mortality of IVD besides increasing bleeding events, although reduced the incidences of MI and stroke early recurrence to a certain extent and did not increase the risk of fatal intracranial bleeding.

Rapid Intravenous Glyceryl Trinitrate in Ischemic Damage (RIGID): A potential neuroprotection strategy for acute ischemic stroke (AIS) patients.

Despite advances in intravenous thrombolysis and endovascular thrombectomy, numerous acute ischemic stroke survivors continue to experience various disability levels. The nitric oxide (NO) donor, Glyceryl Trinitrate (GTN), has been identified as a potential neuroprotective agent against ischemic damage. We evaluated the safety and feasibility of intravenous GTN in AIS patients. Subsequently, we conducted a secondary analysis to assess for possible efficacy of GTN as a neuroprotectant. We conducted a prospective, double-blind, randomized controlled trial in the Stroke Intervention & Translational Center (SITC) in Beijing Luhe Hospital, Capital Medical University (ChiCTR2100046271). AIS patients within 24 h of stroke onset were evenly divided into GTN or control groups (n = 20 each). The GTN group received intravenous GTN (5 mg in 50 ml saline at a rate of 0.4 mg/h for 12.5 h/day over 2 days), while controls were administered an equivalent volume of 0.9% saline. Both groups followed standard Stroke Guidelines for treatment. Safety measures focused on SBP<110 mmHg and headache occurrence. Efficacy was assessed via the 90-day modified rankin score (mRS) and the national institutes of health stroke score (NIHSS). Of the 40 AIS patients, baseline characteristics such as age, gender, risk factors, and pre-mRS scores showed no significant difference between the groups. Safety measures of SBP<110 mmHg and headache occurrence were comparable. Overall, 90-day mRS (1 vs. 1) and NIHSS (1 vs. 1) did not significantly differ between groups. However, the GTN-treated group had a benefit in enhancing NIHSS recovery (△NIHSS 4.5 vs. 3, p = 0.028), indicating that GTN may augment recovery. Subgroup analyses revealed a benefit in the GTN group at the 90-day NIHSS score and △NIHSS follow up for non-thrombolysis patients (1 vs. 2, p = 0.016; 5 vs. 2, p = 0.001). Moreover, the GTN group may benefit mild stroke patients in NIHSS score at 90 day and △NIHSS observed at 90 days (1 vs. 1, p = 0.025; 3 vs. 2 p = 0.002). Overall, while preliminary data suggest GTN might aid recovery in NIHSS improvement, the evidence is tempered due to sample size limitations. The RIGID study confirms the safety and feasibility of intravenous GTN administration for AIS patients. Preliminary data also suggest that the GTN group may provide improvement in NIHSS recovery compared to the control group. Furthermore, a potential benefit for non-thrombolysis patients and those with mild stroke symptoms was identified, suggesting a possible potential role as a tailored intervention in specific AIS subgroups. Due to the limited sample size, further larger RCT will be necessary to replicate these results. TRIAL REGISTRATION: www.chictr.org.cn, identifier: ChiCTR2100046271.

Exploring the Therapeutic Potential of Peritoneal Dialysis (PD) in the Treatment of Neurological Disorders.

Peritoneal dialysis (PD) is a well-established renal replacement therapy commonly employed in clinical practice. While its primary application is in the treatment of kidney disease, its potential in addressing other systemic disorders, including neurological diseases, has garnered increasing interest. This study provides a comprehensive overview of the related technologies, unique advantages, and clinical applications of PD in the context of neurological disorders. By exploring the mechanism underlying PD, its application in neurological diseases, and associated complications, we addressed the feasibility and benefits of PD as an adjunct therapy for various neurological conditions. Our study aims to highlight its role in detoxification and symptom management, as well as its advantages over other universally accepted methods of renal replacement therapy. Our goal is to bring to the spotlight the therapeutic potential of PD in neurological diseases, such as stroke, stimulate further research, and broaden the scope of its application in the clinical setting.

Post-stroke dizziness, depression and anxiety.

OBJECTIVE: Vestibular and psychiatric disorders are very closely related. Previous research shows that the discomfort and dysfunction caused by dizziness in patients can affect psychological processes, leading to anxiety and depression, and the irritation of anxiety and depression can aggravate the discomfort of dizziness. But the causal relationship between dizziness in the recovery period of stroke and Post-stroke depression (PSD) / Post-stroke anxiety (PSA) is not clear. Identifying the causal relationship between them can enable us to conduct more targeted treatments. METHODS: We review the epidemiology and relationship of dizziness, anxiety, and depression, along with the related neuroanatomical basis. We also review the pathophysiology of dizziness after stroke, vestibular function of patients experiencing dizziness, and the causes and mechanisms of PSD and PSA. We attempt to explore the possible relationship between post-stroke dizziness and PSD and PSA. CONCLUSION: The treatment approach for post-stroke dizziness depends on its underlying cause. If the dizziness is a result of PSD and PSA, addressing these psychological factors may alleviate the dizziness. This can be achieved through targeted treatments for PSD and PSA, such as psychotherapy, antidepressants, or anxiolytics, which could indirectly improve dizziness symptoms. Conversely, if PSA and PSD are secondary to vestibular dysfunction caused by stroke, a thorough vestibular function assessment is crucial. Identifying the extent of vestibular impairment allows for tailored interventions. These could include vestibular rehabilitation therapy and medication aimed at vestibular restoration. By improving vestibular function, secondary symptoms like anxiety and depression may also be mitigated.

APOEε4 Carriers Exhibit Objective Cognitive Deficits: A Cross-Sectional Study in a Single Center Trial.

OBJECTIVE: To explore the association between the apolipoprotein E (APOE) genotype and objectively assessed cognitive function. METHODS: In this cross-sectional study, 537 participants underwent a neuropsychological assessment for cognitive function and blood testing for APOE genotype. Based on cognitive test results, participants were stratified into two cohorts: Cognitively Unimpaired participants (CU) and Cognitively Impaired participants (CI). The CI group was further divided into Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD). Furthermore, we conducted age stratification, categorizing participants into three age groups: age 1: <65 years, age 2: 65-75 years, and age 3: >75 years. We assessed the disparities in cognitive function associated with ε4 carrier status across different age brackets. Plasma amyloid-ß levels were measured in a cohort of 294 participants to investigate potential interactions involving ε4 carrier status, diagnosis, sex, or plasma markers. RESULTS: The APOE genotypic distribution among the 537 participants was characterized as follows: ε2/ε2 (5 participants), ε2/ε3 (67), ε2/ε4 (13), ε3/ε3 (330), ε3/ε4 (113), and ε4/ε4 (9). Allele frequencies were: ε3 at 78.21%, ε4 at 13.41%, and ε2 at 8.38%. Notably, the ε4 carrier frequency was markedly elevated in the AD group at 81.8% when compared to MCI at 32.8% and CU at 21.3% (p < 0.05). Within the Cognitively Unimpaired (CU) cohort, the sole discernible contrast between ε4+ and ε4- emerged in STT-B (p < 0.05). Within the CI group, ε4 carriers showed statistically poorer scores as compared to non-ε4 carriers in several cognitive tests (p < 0.05). Age stratification result revealed that, among ε4 carriers, cognitive function scores within the age 3 group were significantly inferior to those of age 1 and age 2 groups (p < 0.05). Plasma amyloid-ß detection was applied to the 294 participants. We tested plasma amyloid-ß (Aß42) and plasma amyloid-ß (Aß40) levels and calculated the Aß42/Aß40 ratio. We found that among female ε4 carriers, both Aß42 and the Aß42/Aß40 ratio were notably lower than their male counterparts (p < 0.05). CONCLUSIONS: The ε3/ε3 was the most prevalent among participants, succeeded by ε3/ε4 and ε2/ε3. The least prevalent were ε2/ε4, ε4/ε4, and ε2/ε2 genotypes. The ε3 was predominant, followed by the ε4 and ε2. Individuals with the ε4 allele exhibited significant cognitive impairment, with an especially high prevalence in AD group at 81.8%. The study unveils a pronounced correlation between the ε4 allele and cognitive deficits, implying its potential role in the advancement and severity of cognitive disorders, notably Alzheimer's disease. Cognitive function declines with age in individuals carrying the ε4, and women are more affected by ε4.

No-reflow after stroke reperfusion therapy: An emerging phenomenon to be explored.

In the field of stroke thrombectomy, ineffective clinical and angiographic reperfusion after successful recanalization has drawn attention. Partial or complete microcirculatory reperfusion failure after the achievement of full patency of a former obstructed large vessel, known as the "no-reflow phenomenon" or "microvascular obstruction," was first reported in the 1960s and was later detected in both experimental models and patients with stroke. The no-reflow phenomenon (NRP) was reported to result from intraluminal occlusions formed by blood components and extraluminal constriction exerted by the surrounding structures of the vessel wall. More recently, an emerging number of clinical studies have estimated the prevalence of the NRP in stroke patients following reperfusion therapy, ranging from 3.3% to 63% depending on its evaluation methods or study population. Studies also demonstrated its detrimental effects on infarction progress and neurological outcomes. In this review, we discuss the research advances, underlying pathogenesis, diagnostic techniques, and management approaches concerning the no-reflow phenomenon in the stroke population to provide a comprehensive understanding of this phenomenon and offer references for future investigations.

The Greater Omentum: Multifaceted Interactions in Neurological Recovery and Disease Progression.

The greater omentum, a unique anatomical structure composed of adipocytes, loose connective tissue, and a dense vascular network. Plays a pivotal role beyond its traditional understanding. It houses specialized immunological units known as 'Milky spots,' making it a key player in immune response. Moreover, the omentum's capacity to enhance tissue perfusion, absorb edema fluid, boost acetylcholine synthesis, and foster neuron repair have rendered it a topic of interest in the context of various diseases, especially neurological disorders. This review provides a comprehensive overview of the intricate anatomy and histology of the greater omentum, casting light on its multifaceted functions and its associations with a spectrum of diseases. With a specific focus on neurological ailments, we delineate the intricate relationship that the omentum shares with other pathologies like stroke and we underly its contribution to serving as a therapeutic agent in neurological disorders. By deciphering the underlying mechanisms and emphasizing areas that demand further investigation. This review aims to spark renewed interest and pave the way for comprehensive studies exploring the greater omentum's potential in neurology and broader medicine overall. Given these diverse interactions that yet remain elusive, we must investigate and understand the nuanced relationship between the greater omentum and pathologies, especially its role in stroke's pathophysiology and therapeutic interventions so as to enhance patient care.

The Modulatory Role of Hypothermia in Post-Stroke Brain Inflammation: Mechanisms and Clinical Implications.

BACKGROUND: Acute ischemic stroke remains a major contributor to mortality and disability worldwide. The use of hypothermia has emerged as a promising neuroprotective strategy, with proven effectiveness in cardiac arrest and neonatal hypoxic-ischemic injury. SUMMARY: This review explores the therapeutic potential of hypothermia in ischemic stroke by examining its impact on post-stroke inflammatory responses. We synthesized evidence from basic and clinical studies to illustrate the inhibitory effects of hypothermia on post-stroke brain inflammation. The underlying mechanisms include modulation of microglial activation and polarization, downregulation of key inflammatory pathways such as MAPKs, NF-KB, and JAK/STAT, protection of the blood-brain barrier integrity, and reduction of immune cell infiltration into the brain. We also discuss the current limitations of hypothermia treatment in clinical practice and highlight future research directions for optimizing protocols and evaluating its clinical efficacy in stroke patients. KEY MESSAGES: Therapeutic hypothermia (TH) has evolved significantly with advancements in medical technologies, especially with the introduction of automated cooling devices, both intravascular and surface based. However, a refined, highly individualized and effective hypothermia protocol may stand robust against the devastating consequences of ischemic stroke, and we think it should become the future development goal.

Hypoxic postconditioning drives protective microglial responses and ameliorates white matter injury after ischemic stroke.

BACKGROUND: Ischemic stroke (IS) is a cerebrovascular disease with high incidence and mortality. White matter repair plays an important role in the long-term recovery of neurological function after cerebral ischemia. Neuroprotective microglial responses can promote white matter repair and protect ischemic brain tissue. AIMS: The aim of this study was to investigate whether hypoxic postconditioning (HPC) can promote white matter repair after IS, and the role and mechanism of microglial polarization in white matter repair after HPC treatment. MATERIALS & METHODS: Adult male C57/BL6 mice were randomly divided into three groups: Sham group (Sham), MCAO group (MCAO), and hypoxic postconditioning group (HPC). HPC group were subjected to 45 min of transient middle cerebral artery occlusion (MCAO) immediately followed by 40 min of HPC. RESULTS: The results showed that HPC reduced the proinflammatory level of immune cells. Furthermore, HPC promoted the transformation of microglia to anti-inflammatory phenotype on the third day after the procedure. HPC promoted the proliferation of oligodendrocyte progenitors and increased the expression of myelination-related proteins on the 14th day. On the 28th day, HPC increased the expression of mature oligodendrocytes, which enhanced myelination. At the same time, the motor neurological function of mice was restored. DISCUSSION: During the acute phase of cerebral ischemia, the function of proinflammatory immune cells was enhanced, long-term white matter damage was aggravated, and motor sensory function was decreased. CONCLUSION: HPC promotes protective microglial responses and white matter repair after MCAO, which may be related to the proliferation and differentiation of oligodendrocytes.

Intensive mannitol slow infusion post-stenting may attenuate stenting-related early adverse effects in patients with cerebral venous sinus stenosis.

AIMS: To analyze intensive slow mannitol poststenting on attenuating stenting-related early adverse effects in cerebral venous sinus stenosis (CVSS). METHODS: This real-world study enrolled subacute or chronic CVSS patients from January 2017 through March 2022 and divided them into DSA only and stenting post-DSA groups. The later group was subdivided into control (without extra mannitol use) and intensive slow mannitol subgroup (immediate extra mannitol 250-500 mL, 2 mL/min infusion post-stenting) after signed informed consent. All data were compared. RESULTS: A total of 95 eligible patients entered into final analysis, in which 37 cases underwent DSA only and 58 cases underwent stenting post-DSA. Finally, 28 patients were entered into intensive slow mannitol subgroup and 30 in control. Stenting group vs. DSA group, HIT-6 scores and WBC counts were higher in the former (both p < 0.001). Intensive slow mannitol subgroup vs. control on the third day post-stenting, a statistically significant reductions were noticed in the former on WBC counts (6.19 ± 1.86 × 109 /L vs. 9.59 ± 2.05 × 109 /L); HIT-6 scores (degree of headache) (40.00 (38.00-40.00) vs. 49.00 (41.75-55.25)) and brain edema surrounding the stent on CT maps (17.86% vs.96.67%), all p < 0.001. CONCLUSIONS: Stenting-related severe headache, inflammatory biomarkers elevation, and brain edema aggravation can be attenuated by intensive slow mannitol infusion.

A novel stroke rehabilitation strategy and underlying stress granule regulations through inhibition of NLRP3 inflammasome activation.

OBJECTIVE: Dynamic changes in ischemic pathology after stroke suggested a "critical window" of enhanced neuroplasticity immediately after stroke onset. Although physical exercise has long been considered a promising strategy of stroke rehabilitation, very early physical exercise may exacerbate brain injury. Since remote ischemic conditioning (RIC) promotes neuroprotection and neuroplasticity, the present study combined RIC with sequential exercise to establish a new rehabilitation strategy for a better rehabilitative outcome. METHODS: A total of 120 adult male Sprague-Dawley rats were used and divided into five groups: (1) sham, (2) stroke, (3) stroke with exercise, (4) stroke with RIC, and (5) stroke with RIC followed by exercise. Brain damage was evaluated by infarct volume, neurological deficit, cell death, and lactate dehydrogenase (LDH) activity. Long-term functional outcomes were determined by grid walk tests, rotarod tests, beam balance tests, forelimb placing tests, and the Morris water maze. Neuroplasticity was evaluated through measurements of both mRNA and protein levels of synaptogenesis (synaptophysin [SYN], post-synaptic density protein-95 [PSD-95], and brain-derived neurotrophic factor [BDNF]) and angiogenesis (vascular endothelial growth factor [VEGF], angiopoietin-1 [Ang-1], and angiopoietin-2 [Ang-2]). Inflammasome activation was measured by concentrations of interleukin-18 (IL-18) and IL-1ß detected by enzyme-linked immunosorbent assay (ELISA) kits, mRNA expressions of NLR pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), IL-18 and IL-1ß, and protein quantities of NLRP3, ASC, cleaved-caspase-1, gasdermin D-N (GSDMD-N), and IL-18 and IL-1ß. Stress granules (SGs), including GTPase-activating protein-binding protein 1 (G3BP1), T cell-restricted intracellular antigen-1 (TIA1), and DEAD-box RNA helicase 3X (DDX3X) were evaluated at mRNA and protein levels. The interactions between DDX3X with NLRP3 or G3BP1 were determined by immunofluorescence and co-immunoprecipitation. RESULTS: Early RIC decreased infarct volumes, neurological deficits, cell death, and LDH activity at post-stroke Day 3 (p < 0.05). All treatment groups showed significant improvement in functional outcomes, including sensory, motor, and cognitive functions. RIC and exercise, as compared to RIC or physical exercise alone, had improved functional outcomes after stroke (p < 0.05), as well as synaptogenesis and angiogenesis (p < 0.05). RIC significantly reduced mRNA and protein expressions of NLRP3 (p < 0.05). SGs formation peaked at 0 h after ischemia, then progressively decreased until 24 h postreperfusion, which was reversed by RIC (p < 0.05). The assembly of SGs consumed DDX3X and then inhibited NLRP3 inflammasome activation. CONCLUSIONS: RIC followed by exercise induced a better rehabilitation in ischemic rats, while early RIC alleviated ischemia-reperfusion injury via stress-granule-mediated inhibition of NLRP3 inflammasome.

High jugular bulb in patients with non-thrombotic internal jugular venous and transverse sinus stenosis: Clues to pathogenesis.

AIMS: Conventional theories for jugular bulb (JB) formation are insufficient to explain the high proportion of high JB in adult patients. We aimed to study features of high JB in patients with non-thrombotic internal jugular venous stenosis (IJVS) and/or transverse sinus stenosis (TSS) to explore the pathogenesis of high JB formation. METHODS: We retrospectively enrolled consecutive patients with the diagnosis of non-thrombotic IJVS and/or TSS. The relationship between IJVS and/or TSS and high JB was explored. Logistic regression analysis was performed to identify potential independent risk factors for high JB. RESULTS: A total of 228 patients were included in the final analyses. The proportions of IJVS, dominant-side IJVS, and non-TSS in dominant-side high JB subgroup were higher than those in nondominant-side high JB subgroup (83.3% vs. 62.5%, p < 0.001; 72.2% vs. 18.3%, p < 0.001; 43.5% vs. 29.2%, p = 0.02). Heights of JBs on dominant sides in IJVS subgroup and non-TSS subgroup were higher than those in non-IJVS subgroup and TSS subgroup (12.93 ± 2.57 mm vs. 11.21 ± 2.76 mm, p < 0.001; 12.66 ± 2.71 mm vs. 11.34 ± 2.73 mm, p = 0.003). Multivariate logistic regression indicated an independent association between dominant-side IJVS and dominant-side high JB (odds ratio, 29.40; 95% confidence interval, 11.04-78.30; p < 0.001). CONCLUSION: IJVS and asymmetric transverse sinus were independently and positively associated with high JB, especially dominant-side IJVS with dominant-side high JB, indicating a potential hemodynamic relationship between IJVS and high JB formation. Conversely, TTS might impede high JB formation.

Association of Early Longitudinal Changes in the Neutrophil-to-Lymphocyte Ratio With Adverse Clinical Outcomes in Acute Ischemic Stroke Patients After Endovascular Treatment.

BACKGROUND: We aim to elucidate the contribution of early dynamic changes in the neutrophil-to-lymphocyte ratio (NLR) to poor clinical outcomes in acute ischemic stroke patients after endovascular treatment (EVT). METHODS: Acute ischemic stroke patients who underwent EVT were consecutively recruited from January 2019 to July 2022. Blood cell counts were sampled at admission and at following 24 hours after EVT. Clinical outcome measures included 3-month functional dependence (modified Rankin scale of 3-6), symptomatic intracranial hemorrhage, and mortality at 7 days and 30 days. Multinomial logistic regressions were used to evaluate the association of changes in the NLR with unfavorable outcomes. RESULTS: A total of 590 patients were included in the final analysis. The multinomial logistic model indicated that the increasing changes in the NLR after EVT was an independent factor for poor outcomes; the adjusted odds ratio was 1.06 (95% confidence interval [CI] 1.03-1.10; P < 0.001) at poor 3-month functional outcomes, 1.07 (95% CI 1.04-1.10; P < 0.001) at symptomatic intracranial hemorrhage, 1.08 (95% CI 1.05-1.12; P < 0.001) at mortality at 7 days, and 1.04 (95% CI 1.02-1.07; P = 0.001) at mortality at 30 days. Areas under the curve of changes in NLR to discriminate adverse outcomes were 0.725, 0.687, 0.664, and 0.659, respectively. The optimal cutoff values were 5.77 (56.6% sensitivity, 81.0% specificity), 6.92 (60.0% sensitivity, 77.0% specificity), 8.64 (51.0% sensitivity, 82.0% specificity), and 8.64 (48.7% sensitivity, 83.0% specificity), respectively. CONCLUSIONS: The NLR in acute ischemic stroke patients increased remarkably independent of successful reperfusion. Elevated changes in the NLR might predict malignant hemorrhagic transformation, adverse functional outcomes, and short-term mortality.