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Stroke remains a significant contributor to global morbidity and mortality, with acute ischemic stroke comprising the majority of cases. Secondary stroke, the recurrent stroke, is often more severe and linked to worse functional outcomes and increased mortality. The secondary prevention of ischemic stroke is crucial for reducing the risk of recurrent events. Significant advancements have been made in secondary prevention strategies in recent years. These include the refinement of antithrombotic regimens, the use of direct oral anticoagulants in managing atrial fibrillation, and the implementation of more aggressive targets for blood pressure, lipid management, and glucose management. Furthermore, emerging therapeutic approaches, such as remote ischemic conditioning and anti-inflammatory agents such as colchicine, have shown promise in reducing stroke recurrence through nontraditional mechanisms. This review summarizes the latest advancements in the secondary prevention of ischemic stroke over the past 5 years, highlighting the key clinical trials and novel interventions. The optimization of traditional risk factor management and the emergence of novel therapeutic methods have provided more options for clinical practice. Future research should focus on identifying the optimal treatment strategies for specific patient subgroups and the clinical translation and application of new therapeutic methods.

Objective: The purpose of this study was to investigate the correlation between residual stenosis rate following percutaneous transluminal angioplasty and stenting (PTAS) and the incidence of ischemic stroke recurrence in patients with symptomatic intracranial atherosclerotic stenosis (sICAS) within 1-year postsurgery. Subjects and Methods: We retrospectively analyzed data from 113 patients with sICAS treated with PTAS between January 1, 2018 and March 31, 2022, at the Stroke Intervention and Translational Center in Beijing Luhe Hospital, Capital Medical University. Outcomes were included stroke and death after stenting within 1 year. Of the sample, 60 patients had middle cerebral artery (MCA) or basilar artery (BA) lesion, and 53 patients had internal carotid artery (ICA) or vertebral artery (VA) lesion. Logistic regression evaluated the association between residual stenosis rate and clinical outcomes. Results: The occurrence rate of perioperative endpoint events was 5.3%. The 3-month rate of endpoint event was 8.8%. A total of 16 endpoint events (14.2%) were observed within a 1-year timeframe. The residual stenosis rate >30% (odds ratio [OR] 3.95; 95% confidence interval [CI]: 1.01–15.38; P = 0.048) and MCA or BA lesion (OR 3.85; 95% CI 1.00–14.89; P = 0.050) independently correlated with ischemic events within 1 year. In the MCA+BA group, residual stenosis rate >30% was observed tended to increase the occurrence of ischemic events within 1 year (OR: 3.35; 95% CI: 0.86–13.10; P = 0.083) after accounting for other confounders. In the ICA+VA group, univariate analysis showed residual stenosis >30% was associated with ischemic events within 1 year (P = 0.028), but no independent association was found after adjusting for other confounding factors. Conclusions: Residual stenosis rate >30% is an independent predictor of stroke recurrence at 1-year postendovascular therapy in patients with sICAS.

Abstract Background Currently, studies on the formation mechanism for the enlargement of arachnoid granulation (AG) are lacking. The impact of dyslipidemia on the formation of multiple large arachnoid granulations (LAGs) was studied in this research. Methods The study included patients diagnosed with cerebral venous sinus stenosis (CVSS) related to LAG. The number of LAGs was assessed via high-resolution black blood magnetic resonance imaging. The relationships between blood lipids and multiple LAGs were explored to evaluate the effects of dyslipidemia on the formation of multiple LAGs. Results A total of 163 participants with a diagnosis of LAG were included. The levels of total cholesterol (TC) (P = 0.004) and low-density lipoprotein cholesterol (LDL-c) (P = 0.01) in the multiple LAGs group were greater than those in the non-multiple LAGs group. Multivariate logistic regression analysis revealed that TC (odds ratio (OR), 2.19; 95% confidence interval (CI), 1.26–3.80; P = 0.006) and LDL-c (OR, 2.18; 95% CI, 1.16–4.07; P = 0.02) were independently associated with multiple LAGs. Conclusions TC and LDL-c are independently related to multiple LAGs, indicating that dyslipidemia may be a potential cause of CVSS. Therefore, monitoring blood lipids may be necessary for patients with LAGs.

The widespread production and disposal of plastics have led to an alarming accumulation of microplastics (MPs) in the environment with significant implications for human health. MPs have infiltrated and accumulated in various ecosystems around the world and consequently in human bodies, posing severe health risks, including the onset of, and acceleration of, neurodegenerative diseases. This review article explores the sources and routes of transmission by which MPs enter the central nervous system, including inhalation and direct penetration of the blood–brain barrier, detection strategies such as engineered nanostructures and gold nanoparticles, and the role of glial cells in exacerbating neurodegenerative diseases such as Alzheimer’s diseases, Parkinson’s diseases, and multiple sclerosis in the presence of MPs. Further, this paper emphasizes a call for action for further investigation and prevention strategies of the impact of MPs including environmental policy changes, advanced detection methods, and potential therapeutic interventions.

Hematologic diseases are considered important contributors to cerebral venous sinus thrombosis (CVST) cases. This retrospective study aims to compare the difference of the clinical and radiological characters between CVST patients with and without hematologic diseases. Consecutive hospitalized CVST patients with hematologic disorders constituted the hematologic disorder group, while that without identifiable risk factors comprised the control group in this study. We systematically documented the various types of hematologic diseases associated with CVST, along with laboratory tests. Clinical manifestations, imaging findings, as well as treatment and prognosis, were recorded. A comparative analysis was conducted between the hematologic disorder group and the control group based on the aforementioned parameters. The final analysis included 97 CVST cases associated with hematologic diseases and 65 cases without any identified risk factors. The spectrum of hematologic diseases in our study ranged from iron-deficiency anemia to acute leukemia. Patients with hematologic disorder showed higher admission mRS, greater thrombotic burden, and higher incidence of stroke and cerebral hemorrhage (p

Background Glyceryl trinitrate (GTN), also known as nitroglycerin, is predominantly recognized as a vasodilator for ischemic heart disease, and its potential neuroprotective properties in acute ischemic stroke remain under exploration. We sought to discover the therapeutic advantages and mechanisms of post‐recanalization GTN administration in acute ischemic stroke. Methods and Results A total of 118 male Sprague–Dawley rats were divided into groups: sham, transient/permanent middle cerebral artery occlusion (MCAO) with or without GTN treatment, and transient/permanent MCAO treated with both GTN and KT5823, an inhibitor of PKG. Acute ischemic stroke was induced by transient MCAO for 2 hours followed by 6 or 24 hours of reperfusion and permanent MCAO (28‐hour MCAO without reperfusion). The study assessed infarct volumes, neurological deficits, glucose metabolism metrics, NO, and cGMP levels via ELISA. mRNA and protein expression of key molecules of hyperglycolysis, gluconeogenesis, endoplasmic reticulum stress as well as signaling molecules (PKG, AMPK) were conducted via reverse transcription polymerase chain reaction and Western blotting, and cell death was assessed with TUNEL and ELISA. GTN significantly reduced cerebral infarct volumes, neurological deficits, and cell death only after transient MCAO. GTN led to a significant reduction in the expression of NO and cGMP levels, key glucose metabolism, endoplasmic reticulum stress‐related genes and proteins, and phosphorylated AMPK while boosting PKG expression, in transient MCAO but not permanent MCAO. The GTN‐induced reduction in glucose metabolites, lactate, and reactive oxygen species was exclusive to transient MCAO groups. Coadministration of GTN and PKG inhibitors reversed the observed GTN benefits. Conclusions GTN induced neuroprotection in transient MCAO by improving glucose metabolism and potentially controlling endoplasmic reticulum stress through the NO‐cGMP‐PKG signaling cascade to inhibit AMPK phosphorylation.

Objectives: Patients with vestibular migraine (VM) show a significant decrease in gray matter cortical regions associated with pain and vestibular processing, as revealed by head functional magnetic resonance imaging. We predict that these changes can be reflected in intentional saccadic eye movements. This study aims to establish whether there are abnormalities in intentional saccadic eye movements in patients with VM. Subjects and Methods: This is a retrospective study involving two groups of patients, including 39 patients in the VM group and 38 patients in the control group. The VM group and control group matched for age and gender were collected from Beijing Luhe Hospital affiliated with Capital Medical University, between June 2021 and May 2022. All patients received antisaccade (AS) and memory-guided saccade (MGS) tasks. Results: Compared with the control group, there were no significant differences in VM group in latency and gain of ASs. However, there were significant differences in the AS error rate between the two groups (right side 44% in VM and 32% in the control group; P = 0.041, left side 41% in VM and 29% in the control group; P = 0.011), with higher error rates observed in the VM group compared to the control group. Compared with the control group, there were no significant differences in the accuracy and final eye position gain of MGSs. However, there were significant differences in the valid saccade accurate percentage of MGS between the two groups (right side 59% in VM and 81% in the control group; P = 0.009, left side 59% in VM and 90% in the control group; P = 0.012), with lower accurate percentages observed in patients with VM compared to the normal control group. Furthermore, the latency of MGS between the two groups differed significantly (right side 677 ms in VM and 491.5 ms in the control group; P = 0.024, left side 670 ms in VM and 555 ms in the control group; P = 0.024), with longer latencies observed in patients with VM compared to normal control group. The results showed that VM disease duration had a positive correlation with the AS error rate (right: P =0.043, r = 0.326; left: P =0.000, r = 0.535). Conclusions: We found abnormalities in the AS and MGS tasks in patients with VM. The duration of VM is positively correlated with the AS error rate. Our study discovered that in addition to headache, dizziness, and autonomic symptoms, VM patients also exhibit impaired intentional saccadic eye movements, which may be related to reduced gray matter volume involved in pain and vestibular processing and cognitive impairment in VM patients.

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.

BackgroundBrain inflammation plays a key role in ischemia/reperfusion (I/R) injury and is the main cause of “ineffective or futile recanalization” after successful mechanical thrombectomy (MT) in acute ischemic stroke (AIS). One of the primary sources of inflammatory cells after AIS are derived from the spleen. As an innovative and potential neuroprotective strategy after stroke, Remote Administration of Hypothermia (RAH) temporarily suppresses immune activities in the spleen, reduces the release of inflammatory cells and cytokines into blood, and thus reversibly diminishes inflammatory injury in the brain.MethodsThis single-center, prospective, randomized controlled study (RCT) is proposed for AIS patients with anterior circulation large vessel occlusion (LVO). Subjects will be randomly assigned to either the control or intervention groups in a 1:1 ratio (n = 40). Participants allocated to the intervention group will receive RAH on the abdomen above the spleen prior to recanalization until 6 h after thrombectomy. All enrolled patients will receive standard stroke Guideline care. The main adverse events associated with RAH are focal cold intolerance and abdominal pain. The primary outcome will assess safety as it pertains to RAH application. The secondary outcomes include the efficacy of RAH on spleen, determined by spleen volumes, blood inflammatory factor (cells and cytokines), and on brain injury, determined by infarction volumes and poststroke functional outcomes.DiscussionThis study aims to examine the safety and preliminary effectiveness of RAH over the spleen during endovascular therapy in AIS patients. The results of this study are expected to facilitate larger randomized clinical trials and hopefully prove RAH administration confers adjuvant neuroprotective properties in AIS treated with MT.Clinical trial registrationhttps://www.chictr.org.cn/. Identifier ChiCTR 2300077052.

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

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.

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.

Stroke remains the leading cause of death and disability in some countries, predominantly attributed to acute ischemic stroke (AIS). While intravenous thrombolysis and endovascular thrombectomy are widely acknowledged as effective treatments for AIS, boasting a high recanalization rate, there is a significant discrepancy between the success of revascularization and the mediocre clinical outcomes observed among patients with AIS. It is now increasingly understood that the implementation of effective cerebral protection strategies, serving as adjunctive treatments to reperfusion, can potentially improve the outcomes of AIS patients following recanalization therapy. Herein, we reviewed several promising cerebral protective methods that have the potential to slow down infarct growth and protect ischemic penumbra. We dissect the underlying reasons for the mismatch between high recanalization rates and moderate prognosis and introduce a novel concept of “multi-target and multi-phase adjunctive cerebral protection” to guide our search for neuroprotective agents that can be administered alongside recanalization therapy.

Abstract Objectives To compare the long‐term safety and efficacy of stenting in correcting cerebral venous sinus stenosis (CVSS) and internal jugular venous stenosis (IJVS). Methods Patients confirmed with CVSS or IJVS by imaging were enrolled in this real‐world study from 2014 through 2021. Clinical characteristics and long‐term outcomes of these two diseases entities post‐stenting were followed up and compared. Results Three hundred and nineteen patients were enrolled in this study, with a mean age of 48.83 years and a BMI of 25.08 on average. In which, 144 patients underwent stenting, the stenotic segments were corrected and the venous blood flow was restored immediately post‐stenting. At 6.15 ± 1.67 days follow‐up, significant improvement was observed in headache, tinnitus, insomnia, ICP, and mean pressure gradient in both groups (all p

Selective endovascular hypothermia has been used to provide cooling-induced cerebral neuroprotection, but current catheters do not support thermally-insulated transfer of cold infusate, which results in an increased exit temperature, causes hemodilution, and limits its cooling efficiency. Herein, air-sprayed fibroin/silica-based coatings combined with chemical vapor deposited parylene-C capping film was prepared on catheter. This coating features in dual-sized-hollow-microparticle incorporated structures with low thermal conductivity. The infusate exit temperature is tunable by adjusting the coating thickness and infusion rate. No peeling or cracking was observed on the coatings under bending and rotational scenarios in the vascular models. Its efficiency was verified in a swine model, and the outlet temperature of coated catheter (75 μm thickness) was 1.8–2.0 °C lower than that of the uncoated one. This pioneering work on catheter thermal insulation coatings may facilitate the clinical translation of selective endovascular hypothermia for neuroprotection in patients with acute ischemic stroke.

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.

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.

In mammals, specificity protein 1 (SP1) was the first Cys2-His2 zinc finger transcription factor to be isolated within the specificity protein and Krüppel-like factor (Sp/KLF) gene family. SP1 regulates gene expression by binding to Guanine–Cytosine (GC)-rich sequences on promoter regions of target genes, affecting various cellular processes. Additionally, the activity of SP1 is markedly influenced by posttranslational modifications, such as phosphorylation, acetylation, glycosylation, and proteolysis. SP1 is implicated in the regulation of apoptosis, cell hypertrophy, inflammation, oxidative stress, lipid metabolism, plaque stabilization, endothelial dysfunction, fibrosis, calcification, and other pathological processes. These processes impact the onset and progression of numerous cardiovascular disorders, including coronary heart disease, ischemia-reperfusion injury, cardiomyopathy, arrhythmia, and vascular disease. SP1 emerges as a potential target for the prevention and therapeutic intervention of cardiac ailments. In this review, we delve into the biological functions, pathophysiological mechanisms, and potential clinical implications of SP1 in cardiac pathology to offer valuable insights into the regulatory functions of SP1 in heart diseases and unveil novel avenues for the prevention and treatment of cardiovascular conditions.

Abstract Background Current methods to evaluate the severity of cerebral venous sinus thrombosis (CVST) lack patient-specific indexes. Herein, a novel scoring method was investigated to estimate the thrombus burden and the intracranial pressure (ICP) of CVST. Methods In this retrospective study from January 2019 through December 2021, we consecutively enrolled patients with a first-time confirmed diagnosis of CVST by contrast-enhanced magnetic resonance venography (CE-MRV) or computed tomography venography (CTV). In these patients, a comprehensive CVST-Score was established using magnetic resonance black-blood thrombus imaging (MRBTI) to estimate the thrombus burden semi-quantitatively. The relationship between CVST-Score and ICP was explored to assess the potential of using the CVST-score to evaluate ICP noninvasively and dynamically. Results A total of 87 patients were included in the final analysis. The CVST-Scores in different ICP subgroups were as follows: 4.29±2.87 in ICP330mmH2O subgroup, respectively (p330mmH2O were 7.15 and 11.62, respectively (P

Highlights Brain hypoxia may be the key point of pathological link between PFO and migraine. NBO may be a feasible promising method on PFO–migraine control. The size of PFO aperture may be not very matched with the severity and the incidence of migraine.

Abstract. Background:. Long-term remote ischemic conditioning (RIC) has been proven to be beneficial in multiple diseases, such as cerebral and cardiovascular diseases. However, the hyperacute and acute effects of a single RIC stimulus are still not clear. Quantitative proteomic analyses of plasma proteins following RIC application have been conducted in preclinical and clinical studies but exhibit high heterogeneity in results due to wide variations in experimental setups and sampling procedures. Hence, this study aimed to explore the immediate effects of RIC on plasma proteome in healthy young adults to exclude confounding factors of disease entity, such as medications and gender. Methods:. Young healthy male participants were enrolled after a systematic physical examination and 6-month lifestyle observation. Individual RIC sessions included five cycles of alternative ischemia and reperfusion, each lasting for 5 min in bilateral forearms. Blood samples were collected at baseline, 5 min after RIC, and 2 h after RIC, and then samples were processed for proteomic analysis using liquid chromatography-tandem mass spectrometry method. Results:. Proteins related to lipid metabolism (e.g., Apolipoprotein F), coagulation factors (hepatocyte growth factor activator preproprotein), members of complement cascades (mannan-binding lectin serine protease 1 isoform 2 precursor), and inflammatory responses (carboxypeptidase N catalytic chain precursor) were differentially altered at their serum levels following the RIC intervention. The most enriched pathways were protein glycosylation and complement/coagulation cascades. Conclusions:. One-time RIC stimulus may induce instant cellular responses like anti-inflammation, coagulation, and fibrinolysis balancing, and lipid metabolism regulation which are protective in different perspectives. Protective effects of single RIC in hyperacute and acute phases may be exploited in clinical emergency settings due to apparently beneficial alterations in plasma proteome profile. Furthermore, the beneficial effects of long-term (repeated) RIC interventions in preventing chronic cardiovascular diseases among general populations can also be expected based on our study findings.

Objective: This study aimed to determine the risk factors associated with short-term neurological decline in acute ischemic stroke patients with large vessel occlusion (LVO) who have undergone successful endovascular recanalization through mechanical thrombectomy. Subjects and Methods: We included 168 LVO patients who had successful recanalization in this study. We collected the patients' demographic data and related disease test results. We noted the National Institutes of Health Stroke Scale (NIHSS) scores at the onset and on the 7th day postonset. After comparing the NIHSS scores at these two time points, we analyzed the correlation between the collected data and the NIHSS scores. We selected the logistic regression model variables based on the correlation significance. We included gender, age, diastolic blood pressure, glycosylated hemoglobin, urea nitrogen, hemoglobin, neutrophil-to-lymphocyte ratio (NLR), low-density lipoprotein, and total protein in a logistic regression model. We used the receiver operating characteristic (ROC) curve to evaluate the predictive power of NLR for deterioration. Results: Mechanical thrombectomy significantly lowered the median NIHSS score of LVO patients on the 7th day of onset, while a subset of patients experienced an increased NIHSS score. Correlation analysis revealed significant correlations between the NIHSS score at onset and diastolic pressure, white blood cell count, neutrophil count, creatinine, and urea nitrogen. On the 7th day postonset, NIHSS scores showed significant correlations with glycosylated hemoglobin, white blood cell count, neutrophil count, NLR, red blood cell count, hemoglobin, and urea nitrogen. Logistic regression analysis further revealed that patients with higher NLR are at significantly increased risk of short-term neurological decline. ROC analysis indicated that a higher NLR can serve as a diagnostic marker for potential adverse outcomes of mechanical thrombectomy. Conclusion: While mechanical thrombectomy substantially improves neurological deficits in LVO patients, some patients still experience deterioration. Higher NLR at stroke onset is associated with short-term neurological function decline in acute LVO patients postsuccessful recanalization.

Background: To investigate the incidence of falls in elderly in nursing homes and to determine the differences in confidence indexes of daily living in the Activities-Specific Balance Confidence Scale (ABC) in elderly fallers or nonfallers. Methods: We conducted a perspective study with elderly (ages >75 years old) from January 1, 2018, to December 31, 2020, living in community nursing homes in Tongzhou district, Beijing. All the participants were able to walk independently, had not experienced any fall episodes, were capable of following commands, and they sufficiently cooperated with the process of the examination. A face-to-face visit or telephone interview was conducted with participants on a regular basis for 12 months. The falling incidence and the differences of ABC scale confidence indexes between fallers and nonfallers were investigated. Results: This study included 87 older adults (67 nonfall participants and 20 fall participants). Falls occurred at a rate of 23 per 100 people per year. The ABC scale index of the faller group was 37%, which indicated very low balance confidence and a high risk of falling. The ABC scale index of the nonfaller group was 80%, which indicated normal balance confidence and no risk of falling. There were significant differences in ABC scale indexes between the faller and nonfaller groups (37% vs. 80%, P = 0.005). There were significant differences in activities such as walking around the house, climbing up and down stairs, picking up slippers from floor, reaching on tiptoes, standing on a chair to reach, walking outside to a nearby car, getting in/out of a car, walking across a parking lot, walking up and down a ramp, walking in a crowded mall between two groups of people, walking in a crowd (risk of bumping into other people), going up an escalator without rail assistance, and walking on an icy sidewalk between the two groups (P < 0.05). Conclusion: Nursing homes have a high rate of falls among older adults. The ABC scale can assess balance confidence and the risk of falling in older adults. To reduce or prevent falls, health-care professionals should screen those who are at high risk of falling and enroll them in a fall prevention program.

The retina is often used to evaluate the vascular health status of eyes and the whole body directly and noninvasively in vivo. Retinal vascular parameters included caliber, tortuosity and fractal dimension. These variables represent the density or geometric characteristics of the vascular network apart from reflecting structural changes in the retinal vessel system. Currently, these parameters are often used as indicators of retinal disease, cardiovascular and cerebrovascular disease. Advanced digital fundus photography apparatus and computer-assisted analysis techniques combined with artificial intelligence, make the quantitative calculation of these parameters easier, objective, and labor-saving.

The retina, as an external extension of the diencephalon, can be directly, noninvasively observed by ocular fundus photography. Therefore, it offers a convenient and feasible mode to study nervous system diseases. Caliber, tortuosity, and fractal dimension, as three commonly used retinal vascular parameters, are not only the reflection of structural changes in the retinal microcirculation but also capture the branching pattern or density changes of the retinal microvascular network. Therefore, it contributes to better reflecting the subclinical pathological changes (e.g., lacunar stroke and small cerebral vascular disease) and predicting the risk of incident stroke and recurrent stroke.

Early rehabilitation is crucial in reducing stroke-related disability, but the optimal training model remains unclear. We conducted a trial comparing different initiation timings and intensities of mobilization strategies after stroke. Results showed that early intensive mobilization had favorable outcomes at 3 months post-stroke, while very early intensive mobilization had poorer chances of favorable outcomes. Our investigation into brain injury mechanisms induced by very early exercise within 24 hours of stroke onset aligned with guidelines advising against high-dose very early mobilization. Additionally, we are studying the effects of various exercise intensities and frequencies on early stroke rehabilitation. Integrated rehabilitation models, such as combining remote ischemic conditioning (RIC) with exercise (RICE), hold promise. Our study found RICE to be safe and feasible for early rehabilitation of acute ischemic stroke patients, and further research is underway to determine its efficacy in a larger sample size. Despite extensive research, identifying the most effective early recovery strategies remains a complex challenge, necessitating ongoing work in the field of early rehabilitation after stroke.

The no-reflow phenomenon (NRP) after successful vascular recanalization in acute ischemic stroke (AIS) has become a major cause of poor clinical prognosis and ineffective recanalization. However, there is currently no clear definition or unified clinical assessment method for the NRP. Therefore, it is urgent to clarify the clinical evaluation criteria for the NRP and develop new no-reflow evaluation techniques so that remedial treatment can be applied to AIS patients suffering from the NRP. In this brief review, a variety of NRP assessment methods and defining criteria for clinical practice are presented.

Oligodendrocytes (OLs), the myelin-forming cells of the central nervous system, are integral to axonal integrity and function. Hypoxia-ischemia episodes can cause severe damage to these vulnerable cells through excitotoxicity, oxidative stress, inflammation, and mitochondrial dysfunction, leading to axonal dystrophy, neuronal dysfunction, and neurological impairments. OLs damage can result in demyelination and myelination disorders, severely impacting axonal function, structure, metabolism, and survival. Adult-onset stroke, periventricular leukomalacia, and post-stroke cognitive impairment primarily target OLs, making them a critical therapeutic target. Therapeutic strategies targeting OLs, myelin, and their receptors should be given more emphasis to attenuate ischemia injury and establish functional recovery after stroke. This review summarizes recent advances on the function of OLs in ischemic injury, as well as the present and emerging principles that serve as the foundation for protective strategies against OLs deaths.

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: 75 years. We assessed the disparities in cognitive function associated with ε4 carrier status across different age brackets. Plasma amyloid-β 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-β detection was applied to the 294 participants. We tested plasma amyloid-β (Aβ42) and plasma amyloid-β (Aβ40) levels and calculated the Aβ42/Aβ40 ratio. We found that among female ε4 carriers, both Aβ42 and the Aβ42/Aβ40 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.

Abstract Background Although endovascular recanalization therapy demonstrates robust clinical efficacy in acute ischemic stroke (AIS), not all victims of these cerebrovascular accidents can benefit from it and achieve a favorable prognosis after successful reperfusion. Therefore, alternative neuroprotective strategies are urgently needed for AIS patients after vessel recanalization. Nitric oxide (NO) levels are low after AIS and NO donor drugs may be neuroprotective against cerebral ischemia–reperfusion injury. Glyceryl trinitrate (GTN), often used in the clinic as a NO donor, may provide a novel neuroprotective strategy. This rationale, design, and protocol for a prospective pilot study plans to explore the preliminary safety, feasibility, and neuroprotective benefits of Arterial Glyceryl Trinitrate in Acute Ischemic Stroke after Thrombectomy for Neuroprotection (AGAIN). Methods AGAIN, a prospective RCT, is proposed for AIS patients after mechanical thrombectomy. Subjects will be randomly assigned in a 1:1 fashion (n = 40) to either the control group or the intervention group. Participants assigned to the intervention group will be administered 800 μg GTN in the catheter immediately after recanalization, whereas those in the control group will be administered the same volume of normal saline. All participants from either group will be given concurrent treatment with standard of care therapies in accordance with the current guidelines for stroke management. The primary outcome is safety [symptomatic intracranial hemorrhage (ICH), hypotension, neurological deterioration, ICH, fatal ICH, as well as headache, tachycardia, emesis, and seizures], whereas secondary outcomes included changes in poststroke functional outcomes, infarction volumes, and blood nitrate index detection. Discussions This study is a prospective randomized controlled trial to test the safety and efficacy of intra-arterial GTN in AIS patients after endovascular therapy. The results from this study will give insight for future GTN studies and new neuroprotective strategies for future AIS treatment strategies. Trial registration number ChiCTR2100045254. Registered on March 21, 2021.

Abstract Background and purpose The present strategies regarding poststent management for cerebral venous sinus stenosis (CVSS) are inconsistent. Herein, we compared the safety and efficacy of oral anticoagulants (OACs) plus single antiplatelet therapy and dual antiplatelet therapy for CVSS poststenting. Methods A real-world observational study conducted from January 2009 through October 2019 enrolled patients who were diagnosed with CVSS and received stenting. Patients were divided into two groups according to the management they received poststenting. Group 1: OACs plus a single antiplatelet agent (clopidogrel 75 mg or aspirin 100 mg) and Group 2: dual antiplatelet therapy (clopidogrel 75 mg plus aspirin 100 mg). The safety (such as major or minor bleeding or venous thrombosis) and efficacy (the incidences of cerebral venous sinus restenosis, intrastent thrombosis, or stent displacement) of the two groups were compared. Results There were a total of 110 eligible patients in the final analysis, including 79 females and 31 males with a mean age of 43.42 ± 13.23 years. No major bleeding or venous thrombosis occurred in either of the two groups. Two minor bleeding events occurred in group 2 (one with subcutaneous bleeding points in both lower limbs, another with submucosal bleeding in the mouth), whereas no bleeding events occurred in Group 1. In addition, at the 1-year follow-up, one case of intraluminal restenosis and two cases of in-stent thrombi occurred in Group 2, while none occurred in Group 1. Neither stenosis at stent-adjacent segments nor stent migration was detected in either group during the 1-year following stent placement. Conclusion OACs plus single antiplatelet therapy and dual antiplatelet therapy alone are both safe and efficacious management strategies after CVSS stent placement. The former may have more advantages than the latter for inhibiting intrastent thrombosis. However, further research by larger, multicenter clinical trials is needed.

BackgroundAlthough endovascular mechanical thrombectomy demonstrates clinical efficacy in posterior circulation acute ischemic stroke (AIS), only one third of these patients attain functional independence with a third of patients’ expiring despite vascular recanalization. Neuroprotection strategies, such as therapeutic hypothermia (TH) have been considered a promising adjunctive treatment in AIS. We propose the following rationale, design and protocol for a prospective randomized controlled trial (RCT) aimed to determine whether Vertebrobasilar Artery Cooling Infusion (VACI) improves functional outcomes in posterior circulation AIS patients post mechanical thrombectomy.MethodsSubjects in the study will be assigned randomly to either the cooling infusion or the control group in a 1:1 ratio (n = 40). Patients allocated to the cooling infusion group will receive 300 ml cool saline at 4C through the catheter (30 ml/min) into vertebral artery after thrombectomy. The control group will receive the same volume of 37C saline. All patients enrolled will receive standard care according to current guidelines for stroke management. The primary outcome is symptomatic intracranial hemorrhage (ICH), whereas the secondary outcomes include functional outcome score, infarction volume, mortality, ICH, fatal ICH, cerebral vasospasm, coagulation abnormality, pneumonia and urinary infection.DiscussionsThis study will determine the preliminary safety, feasibility, and neuroprotective benefits of VACI in posterior circulation AIS patients with reperfusion therapy. The results of this study may provide evidence for VACI as a new therapy in posterior circulation AIS.Clinical Trial Registration:www.chictr.org.cn, ChiCTR2200065806, registered on November 15, 2022.

Abstract Purpose Unilateral jugular stenosis is easily mistaken as jugular hypoplasia for their similar jugular appearances. This study aimed to propose a scheme to differentiate acquired internal jugular vein stenosis (IJVS) from congenital jugular variation through two case examples. Methods We presented a dynamic evolution process of the IJVS formation, through a case of a 17-year-old female with paroxysmal nocturnal hemoglobinuria (PNH)-associated right internal jugular venous thrombosis (IJVT), which resulted in post-thrombotic IJVS in the rare context of rapid recanalization. Meanwhile, we compared her images with images of a 39-year-old healthy male with hypoplastic IJV to determine the differences between the acquired IJVS and congenital dysplasia. Results Based on the first case, we noticed the whole formative process of acquired IJVS from nothing to something. Meantime, we found that acquired IJVS was surrounded by abnormal corkscrew collaterals as imaged on contrast-enhanced magnetic resonance venography (CE-MRV), and the ipsilateral jugular foramen (JF) was normal-sized as displayed on computer tomography (CT). Conversely, jugular hypoplasia was with ipsilateral stenotic JF and without serpentine collaterals. Conclusion JF morphology and venous collaterals may be deemed as surrogate identifiers to distinguish acquired unilateral IJVS from jugular hypoplasia.

Myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disease (MOGAD) is an independent inflammatory demyelinating disease. A rare phenotype of MOGAD is cerebral cortical encephalitis (CCE). This case report presents unilateral recurrent cerebral cortical encephalitis (CCE) with positive anti-MOG antibodies from a 55 year old man who was admitted with headache, fever and aphasia. This case highlights the findings of hyperintense lesions in the cortex of the right temporal gyrus with slight swelling on T2 FLAIR and anti MOG antibodies in serum (1:20) and CSF (1:80) when the patient presented again to hospital after the initial improvement with IVIG and glucocorticoids. In addition, the patient was found to have atrophy of the whole brain, especially the right temporal lobe, after becoming symptom-free with glucocorticoids. In summary, anti-MOG-associated CCE can be diagnosed with headache, fever, and seizures associated with the presence of anti-MOG antibodies. Unilateral CCE is a special clinical feature of MOGAD and cerebral atrophy can be found. Steroid therapy remains to be the standard treatment.

Stroke kills or disables approximately 15 million people worldwide each year. It is the leading cause of brain injury, resulting in persistent neurological deficits and profound physical handicaps. In spite of over 100 clinical trials, stroke treatment modalities are limited in applicability and efficacy, and therefore, identification of new therapeutic modalities is required to combat this growing problem. Poststroke oxidative damage and lactic acidosis are widely-recognized forms of brain ischemia/reperfusion injury. However, treatments directed at these injury mechanisms have not been effective. In this review, we offer a novel approach combining these well-established damage mechanisms with new insights into brain glucose handling. Specifically, emerging evidence of brain gluconeogenesis provides a missing link for understanding oxidative injury and lactate toxicity after ischemia. Therefore, dysfunctional gluconeogenesis may substantially contribute to oxidative and lactate damage. We further review that hypothermia initiated early in ischemia and before reperfusion may ameliorate gluconeogenic dysfunction and subsequently provide an important mechanism of hypothermic protection. We will focus on the efficacy of pharmacologically assisted hypothermia and suggest a combination that minimizes side effects. Together, this study will advance our knowledge of basic mechanisms of ischemic damage and apply this knowledge to develop new therapeutic strategies that are desperately needed in the clinical treatment of stroke.

Despite decades of research, stroke therapies are limited to recanalization therapies that can only be used on

The impact of stroke, currently the second leading cause of death worldwide, continues to worsen, and even those that survive can have persistent neurological deficits. A potentially significant implication may be due to hyperglycemia, found in one-third of all acute ischemic stroke (AIS) patients. However, prior studies reported conflicting information about the impact of hyperglycemia on poststroke prognosis, likely due to different measurements of stress-induced hyperglycemia. The glucose-to-glycated hemoglobin ratio is an index of stress-induced hyperglycemia after AIS that better quantifies acute changes in blood glucose, as opposed to absolute variations in glucose levels. Moderate blood glucose reductions might counteract the negative effects of hyperglycemia and glycemic control medications can also play a role in neuroprotection. The liver is the main organ that functions to maintain energy and glucose metabolism and the effects of AIS can reach far peripheral organs, including the liver. In this review, we highlighted the mechanism responsible for acute poststroke hyperglycemia, a hepatic inflammatory pathway that results in hepatic gluconeogenesis and reduced hepatic insulin sensitivity. Hepatitis cascades lead to hepatic gluconeogenesis, and targeted therapy with antihyperglycemic drugs has the potential to improve stroke prognosis and recovery.

ObjectiveThis study assesses whether stress-induced hyperglycemia is a predictor of poor outcome at 3 months for patients with acute ischemic stroke (AIS) treated by endovascular treatment (EVT) and impacted by their previous blood glucose status.MethodsThis retrospective study collected data from 576 patients with AIS due to large vessel occlusion (LVO) treated by EVT from March 2019 to June 2022. The sample was composed of 230 and 346 patients with and without diabetes mellitus (DM), respectively, based on their premorbid diabetic status. Prognosis was assessed with modified Rankin Scale (mRS) at 3-month after AIS. Poor prognosis was defined as mRS>2. Stress-induced hyperglycemia was assessed by fasting glucose-to-glycated hemoglobin ratio (GAR). Each group was stratified into four groups by quartiles of GAR (Q1–Q4). Binary logistic regression analysis was used to identify relationship between different GAR quartiles and clinical outcome after EVT.ResultsIn DM group, a poor prognosis was seen in 122 (53%) patients and GAR level was 1.27 ± 0.44. These variables were higher than non-DM group and the differences were statistically significant (p < 0.05, respectively). Patients with severe stress-induced hyperglycemia demonstrated greater incidence of 3-month poor prognosis (DM: Q1, 39.7%; Q2, 45.6%; Q3, 58.6%; Q4, 68.4%; p = 0.009. Non-DM: Q1, 31%; Q2, 32.6%; Q3, 42.5%; Q4, 64%; p < 0.001). However, the highest quartile of GAR was independently associated with poor prognosis at 3 months (OR 3.39, 95% CI 1.66–6.96, p = 0.001), compared to the lowest quartile in non-DM patients after logistic regression. This association was not observed from DM patients.ConclusionThe outcome of patients with acute LVO stroke treated with EVT appears to be influenced by premorbid diabetes status. However, the poor prognosis at 3-month in patients with DM is not independently correlated with stress-induced hyperglycemia. This could be due to the long-term damage of persistent hyperglycemia and diabetic patients’ adaptive response to stress following acute ischemic damage to the brain.

Abstract Pre‐stroke exercise conditioning reduces neurovascular injury and improves functional outcomes after stroke. The goal of this study was to explore if post‐stroke exercise conditioning (PostE) reduced brain injury and whether it was associated with the regulation of gluconeogenesis. Adult rats received 2 h of middle cerebral artery (MCA) occlusion, followed by 24 h of reperfusion. Treadmill activity was then initiated 24 h after reperfusion for PostE. The severity of the brain damage was determined by infarct volume, apoptotic cell death, and neurological deficit at one and three days after reperfusion. We measured gluconeogenesis including oxaloacetate (OAA), phosphoenolpyruvate (PEP), pyruvic acid, lactate, ROS, and glucose via ELISA, as well as the location and expression of the key enzyme phosphoenolpyruvate carboxykinase (PCK)‐1/2 via immunofluorescence. We also determined upstream pathways including forkhead transcription factor (FoxO1), p‐FoxO1, 3‐kinase (PI3K)/Akt, and p‐PI3K/Akt via Western blot. Additionally, the cytoplasmic expression of p‐FoxO1 was detected by immunofluorescence. Compared to non‐exercise control, PostE (*p

Background. Abdominal aortic occlusion (AAO) occurs frequently and causes ischemia/reperfusion (I/R) injury to distant organs. In this study, we aimed to investigate whether AAO induced I/R injury and subsequent damage in cardiac and neurologic tissue. We also aimed to investigate the how length of ischemic time in AAO influences reactive oxygen species (ROS) production and inflammatory marker levels in the heart, brain, and serum. Methods. Sixty male C57BL/6 mice were used in this study. The mice were randomly divided into either sham group or AAO group. The AAO group was further subdivided into 1–4 hr groups of aortic occlusion times. The infrarenal abdominal aorta was clamped for 1–4 hr depending on the AAO group and was then reperfused for 24 hr after clamp removal. Serum, hippocampus, and left ventricle tissue samples were then subjected to biochemical and histopathological analyses. Results. AAO-induced I/R injury had no effect on cell necrosis, cell apoptosis, or ROS production. However, serum and hippocampus levels of malondialdehyde (MDA) and lactate dehydrogenase (LDH) increased in AAO groups when compared to sham group. Superoxide dismutase and total antioxidant capacity decreased in the serum, hippocampus, and left ventricle. In the serum, AAO increased the level of inducible nitric oxide synthase (iNOS) and decreased the levels of anti-inflammatory factors (such as arginase-1), transforming growth factor- β1 (TGF-β1), interleukin 4 (IL-4), and interleukin 10 (IL-10). In the hippocampus, AAO increased the levels of tumor necrosis factor (TNF-α), interleukin 1β (IL-1β), interleukin 6 (IL-6), IL-4, and IL-6, and decreased the level of TGF-β1. In the left ventricle, AAO increased the level of iNOS and decreased the levels of TGF-β1, IL-4, and IL-10. Conclusions. AAO did not induce cell necrosis or apoptosis in cardiac or neurologic tissue, but it can cause inflammation in the serum, brain, and heart.

Background. Cerebrovascular disease (CVD) is recognized as the leading cause of permanent disability worldwide. Depressive disorders are associated with increased incidence of CVD. The goal of this study was to establish a chronic restraint stress (CRS) model for mice and examine the effect of stress on cerebrovascular inflammation and oxidative stress responses. Methods. A total of forty 6-week-old male C57BL/6J mice were randomly divided into the CRS and control groups. In the CRS group (n=20), mice were placed in a well-ventilated Plexiglas tube for 6 hours per day for 28 consecutive days. On day 29, open field tests (OFT) and sucrose preference tests (SPT) were performed to assess depressive-like behaviors for the two groups (n=10/group). Macrophage infiltration into the brain tissue upon stress was analyzed by measuring expression of macrophage marker (CD68) with immunofluorescence in both the CRS and control groups (n=10/group). Cerebral microvasculature was isolated from the CRS and controls (n=10/group). mRNA and protein expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), and macrophage chemoattractant protein-1 (MCP-1) in the brain vessels were measured by real-time PCR and Western blot (n=10/group). Reactive oxygen species (ROS), hydrogen peroxide (H2O2), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activities were quantified by ELISA to study the oxidative profile of the brain vessels (n=10/group). Additionally, mRNA and protein expressions of NOX subunits (gp91phox, p47phox, p67phox, and p22phox) in the cerebrovascular endothelium were analyzed by real-time PCR and Western blot (n=10/group). Results. CRS decreased the total distances (p

ObjectiveRehabilitation is essential in reducing stroke disability and should be performed as early as possible. Exercise is an established and effective rehabilitation method; however, its implementation has been limited as its very early use exacerbates cerebral injury and is restricted by patients' unstable conditions and disabilities. Remote ischemic conditioning (RIC) is a passive and accessible therapy in acute phases of stroke and appears to have similar neuroprotective effects as exercise. This study assessed the safety and feasibility of the novel rehabilitation strategy—early RIC followed by exercise (RICE) in acute ischemic stroke (AIS).MethodsWe conducted a single-center, double-blinded, randomized controlled trial with AIS patients within 24 h of stroke onset or symptom exacerbation. All enrolled patients were randomly assigned, at a ratio of 1:1, to either the RICE group or the sham-RICE group (sham RIC with exercise). Each group received either RIC or sham RIC within 24 h after stroke onset or symptom exacerbation, once a day, for 14 days. Both groups started the exercise routine on day 4, twice daily, for 11 total days. The safety endpoints included clinical deterioration, recurrence of stroke, hemorrhagic transformation, complications, and adverse events resulting from RICE during hospitalization. The efficacy endpoints [Modified Rankin Scale (mRS) score, National Institutes of Health Stroke Scale (NIHSS) score, Barthel Index, and walking ability] were evaluated at admission and 90 days after stroke onset.ResultsForty AIS patients were recruited and completed the study. No significant differences in baseline characteristics were found between the two groups, which included risk factors, stroke severity at admission, pre-morbid disability, and other special treatments. No significant differences were found in the safety endpoints between two groups. Excellent recovery (mRS 0–2) at 3 months was obtained in 55% of the patients with RICE as compared 40% in sham group, but it did not reach a significant level.ConclusionsRICE was safe and feasible for AIS patients, and seems to be a promising early stroke rehabilitation. The results of this study suggest a need for a future randomized and controlled multicenter trial with a larger sample size to determine the efficacy of RICE.

Branch atheromatous disease (BAD) is a subtype of ischemic stroke caused by perforating arteries occlusion due to proximal atherosclerosis of the arteries. Early neurological deterioration and recurrent stereotyped transient ischemic attacks are typical clinical manifestations of BAD. The optimal treatment for BAD has not been determined. This article explores a possible mechanism of BAD and effective treatment measures to prevent early progression and attack of transient ischemic events. This article explains the current status of intravenous thrombolysis, tirofiban, and argatroban for BAD and subsequent prognosis.

It is well known that stress can increase the risk of heart attack and stroke although the exact way it does this is unknown. This information is particularly more relevant in a post COVID-19 era where healthcare workers are increasingly facing more stressful working conditions. Thus, it is important to look into alternative methods to deal with stress including meditation and yoga which have shown potential.

ObjectiveSleep disturbances are common non-motor symptoms of Parkinson's disease. The symptoms affect the quality of patients' life by impeding normal sleep cycles and causing excessive daytime sleepiness. Remote Ischemic Conditioning (RIC) is a therapy often used for ischemic stroke patients to minimize infarct size and maximize post-stroke neurological function. Animal experiments have shown that RIC plays a protective role for retinal ganglion cells and other critical areas of the brain of Parkinson's disease. However, whether RIC improves excessive daytime sleepiness (EDS) for patients with Parkinson's disease remains to be determined.MethodsThis is a single-center, double-blind, and randomized controlled trial, which includes patients with Parkinson's disease with EDS. All recruited patients will be randomly assigned either to the RIC or the control group (i.e., sham-RIC) with 20 patients in each group. Both groups receive RIC or sham-RIC treatment once a day for 28 days within 24 h of enrollment. Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Parkinson Disease Sleep Scale-2 (PDSS-2), Parkinson's Disease Questionnaire39 (PDQ39) score scales, and adverse events, such as inability to tolerate the treatment leading to suspension of the study or objective signs of tissue or neurovascular injury caused by RIC and/or sham-RIC are evaluated at 7, 14, 28, and 90 days after enrollment.ResultsThe primary goal of this study is to assess the feasibility of the treatments in patients with Parkinson's disease by measuring serious RIC-related adverse events and any reduced incidence of adverse events during the trial and to study potential efficacy, improvement of patients' excessive daytime sleepiness, quality of life-based on ESS, PSQI, PDSS-2, and PDQ39 scores. The secondary goal is to confirm the safety of the treatments.ConclusionThis study is a prospective randomized controlled trial to determine the safety, feasibility, and potential efficacy of RIC for patients with Parkinson's disease associated with EDS.

Cerebral venous thrombosis (CVT) is a rare type of venous thromboembolism (VTE). It is an important cause of stroke in young adults and children. Severe CVT, which is characterized by cerebral venous infarction or hemorrhage, seizures, or disturbance of consciousness, has more severe clinical manifestations and a worse prognosis. It is commonly believed that the onset of severe CVT gave credit to venous return disorder, with the underlying pathogenesis remaining unclear. There is increasing evidence suggesting that an inflammatory response is closely associated with the pathophysiology of severe CVT. Preclinical studies have identified the components of neuroinflammation, including microglia, astrocytes, and neutrophils. After CVT occurrence, microglia are activated and secrete cytokines (e.g., interleukin-1β and tumor necrosis factor-α), which result in a series of brain injuries, including blood-brain barrier disruption, brain edema, and cerebral venous infarction. Additionally, astrocytes are activated at the initial CVT stage and may interact with microglia to exacerbate the inflammatory response. The extent of cerebral edema and neutrophil recruitment increases temporally in the acute phase. Further, there are also changes in the morphology of inflammatory cells, expression of inflammatory mediators, and inflammatory pathway molecules with CVT progression. Lately, some clinical research suggested that some inflammation-related biomarkers are of great value in assessing the course, severity, and prognosis of severe CVT. Moreover, basic and clinical research suggested that anti-inflammatory therapy might hold promise in severe CVT. This study reviews the current literature regarding the involvement of inflammation in the pathophysiology and anti-inflammatory interventions of severe CVT, which would contribute to informing the pathophysiology mechanism and laying a foundation for exploring novel severe CVT therapeutic strategies.

ObjectiveThe present study sought to differentiate multiple sclerosis and neuromyelitis optica spectrum disorder patients at their first attack by describing and distinguishing their clinical features, radiographic characteristics, and immunologic characteristics of serum and cerebrospinal fluid.MethodsWe retrospectively studied 58 patients with multiple sclerosis (MS) and 52 patients with neuromyelitis optica spectrum disorder (NMOSD) by referencing brainstem lesions as the prodromal events. Their demographics and presentation at the time of the first attack was evaluated including their gender, age, clinical features of the first attack, the expanded disability status scale (EDSS), brainstem lesion(s) by head MRI, and immunological indices of serum and cerebrospinal fluid.ResultsThe NMOSD group had more female patients (4.8 vs. 1.9, p < 0.05), and was older than the MS group (37.81 ± 16.60 vs. 27.57 ± 11.17, p