Cerebral autoregulation: A reliable predictor of prognosis in patients receiving intravenous thrombolysis.

AIMS: To investigate the characteristics of dynamic cerebral autoregulation (dCA) after intravenous thrombolysis (IVT) and assess the relationship between dCA and prognosis. METHODS: Patients with unilateral acute ischemic stroke receiving IVT were prospectively enrolled; those who did not were selected as controls. All patients underwent dCA measurements, by quantifying the phase difference (PD) and gain, at 1-3 and 7-10 days after stroke onset. Simultaneously, two dCA-based nomogram models were established to verify the predictive value of dCA for patients with mild-to-moderate stroke. RESULTS: Finally, 202 patients who received IVT and 238 who did not were included. IVT was positively correlated with higher PD on days 1-3 and 7-10 after stroke onset. PD values in both sides at 1-3 days after stroke onset and in the affected side at 7-10 days after onset were independent predictors of unfavorable outcomes in patients who received IVT. Additionally, in patients with mild-to-moderate stroke who received IVT, the dCA-based nomogram models significantly improved the risk predictive ability for 3-month unfavorable outcomes. CONCLUSION: IVT has a positive effect on dCA in patients with acute stroke; furthermore, dCA may be useful to predict the prognosis of patients with IVT.

Compromised Dynamic Cerebral Autoregulation in Patients with Restless Legs Syndrome.

Background: Restless legs syndrome (RLS) is a prevalent sensorimotor nervous system disorder in patients accompanied with insomnia, blood pressure fluctuation, and sympathetic dysfunction. These symptoms may disrupt cerebral hemodynamics. Dynamic cerebral autoregulation (dCA) describes the temporary response of cerebrovascular system to abrupt fluctuations in blood pressure, which keep cerebral blood flow stable and serve as a marker of cerebrovascular system ability. Objective: This research aimed to assess dCA in RLS patients. Methods: In this study, RLS patients were recruited and subsequently classified into four groups (mild, moderate, severe, and very severe) based on the International RLS Rating Scale (IRLS). Healthy controls matched for age and sex were enrolled. All participants were evaluated dCA by assessing phase difference (PD). A portion of patients with RLS was reassessed for dCA after one month of medication therapy (pramipexole [0.125 mg/day] and gabapentin [300 mg/day]). Results: There were altogether 120 patients with RLS and 30 controls completed the polysomnography and dCA assessment. PD was lower in the moderate, severe, and very severe RLS groups than that in the controls and mild RLS groups. Periodic limb movement index (PLMI), arousal index, and IRLS all showed a linear correlation with PD in RLS patients. Additionally, PD increased in RLS patients after therapy. Conclusion: The dCA was compromised in moderate, severe, and very severe RLS patients and was negatively correlated with the IRLS, arousal index, and PLMI. After 1 month of therapy, dCA improved in RLS patients.

Blood-brain barrier disruption and hemorrhagic transformation in acute stroke before endovascular reperfusion therapy.

Background and purpose: Early blood-brain barrier (BBB) disruption in patients with acute ischemic stroke (AIS) can be detected on perfusion computed tomography (PCT) images before undergoing reperfusion therapy. In this study, we aimed to determine whether early disruption of the BBB predicts intracranial hemorrhage transformation (HT) in patients with AIS undergoing endovascular therapy and further identify factors influencing BBB disruption. Methods: We retrospectively analyzed general clinical and imaging data derived from 159 consecutive patients with acute anterior circulation stroke who were admitted to the Department of Neurology of the First Hospital of Jilin University, and who underwent endovascular treatment between January 1, 2021, and March 31, 2023. We evaluated the relationship between BBB destruction and intracranial HT before endovascular reperfusion therapy and examined the risk factors for early BBB destruction. Results: A total of 159 patients with assessable BBB leakage were included. The median (interquartile range, IQR) age was 63 (54-70) years, 108 (67.9%) patients were male, and the median baseline National Institutes of Health Stroke Scale (NHISS) score was 12 (10-15). Follow-up non-contrast computed tomography (NCCT) detected HT in 63 patients. After logistic regression modeling adjustment, we found that BBB leakage in the true leakage area was slightly more than 2-fold risk of HT (odds ratio [OR], 2.01; 95% confidence interval [CI] 1.02-3.92). Heart rate was also associated with HT (OR, 1.03, 95% CI, 1.00-1.05). High Blood-brain barrier permeability (BBBP) in the true leakage area was positively correlated with infarct core volume (OR, 1.03; 95% CI, 1.01-1.05). Conclusion: Early BBB destruction before endovascular reperfusion therapy was associated with HT, whereas high BBBP correlated positively with infarct core volume.

Effects of a Planned Web-Based Educational Intervention Based on the Health Belief Model for Patients With Ischemic Stroke in Promoting Secondary Prevention During the COVID-19 Lockdown in China: Quasi-Experimental Study.

Background: Some common modified vascular risk factors remain poorly controlled among stroke survivors, and educational programs may help improve these conditions. Objective: This study aimed to evaluate the effect of a planned web-based educational intervention based on the health belief model (HBM) in promoting secondary prevention among patients with ischemic stroke. Methods: An evaluation-blinded quasi-experimental trial with a historical control group was conducted. Patients admitted from March to June 2020 were assigned to the historical control group, and patients admitted from July to October 2020 were assigned to the intervention group. The control group received routine health management. The intervention group received 6 additional sessions based on the HBM via Tencent Meeting, an audio and video conferencing application, within 3 months after discharge. Sessions were held every 2 weeks, with each session lasting approximately 40 minutes. These sessions were conducted in small groups, with about 8 to 10 people in each group. The primary outcomes were changes in blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), hemoglobin A1c (HbA1c), and the proportion of patients achieving the treatment target. The secondary outcomes were medication adherence, assessed with the Morisky Medicine Adherence Scale (MMAS), and disability, assessed with the modified Rankin scale. Results: In total, 315 patients experiencing their first-ever stroke were analyzed. More patients in the intervention group had controlled BP (41.9% vs 28.4%; adjusted odds ratio [aOR] 1.93; P=.01), LDL-C (83.1% vs 67.7%; aOR 2.66; P=.001), and HbA1c (91.9% vs 83.9%; aOR: 3.37; P=.04) levels as well as a significant postintervention decrease in the systolic BP (adjusted ß -3.94; P=.02), LDL-C (adjusted ß -0.21; P=.008), and HbA1c (adjusted ß -0.27; P<.001), compared with control groups. Significant between-group differences were observed in medication adherence (79.4% vs 63.2%; aOR 2.31; P=.002) but not in favorable functional outcomes. Conclusions: A web-based education program based on the HBM may be more effective than current methods used to educate patients having strokes on optimal vascular risk factors and medication adherence.

Emerging strategies for nerve repair and regeneration in ischemic stroke: neural stem cell therapy.

Ischemic stroke is a major cause of mortality and disability worldwide, with limited treatment options available in clinical practice. The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function. Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect. Neural stem cells regulate multiple physiological responses, including nerve repair, endogenous regeneration, immune function, and blood-brain barrier permeability, through the secretion of bioactive substances, including extracellular vesicles/exosomes. However, due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation, limitations in the treatment effect remain unresolved. In this paper, we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke, review current neural stem cell therapeutic strategies and clinical trial results, and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells. We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.

Nanodrug delivery systems for regulating microglial polarization in ischemic stroke treatment: A review.

The incidence of ischemic stroke (IS) is rising in tandem with the global aging population. There is an urgent need to delve deeper into the pathological mechanisms and develop new neuroprotective strategies. In the present review, we discuss the latest advancements and research on various nanodrug delivery systems (NDDSs) for targeting microglial polarization in IS treatment. Furthermore, we critically discuss the different strategies. NDDSs have demonstrated exceptional qualities to effectively permeate the blood-brain barrier, aggregate at the site of ischemic injury, and target specific cell types within the brain when appropriately modified. Consequently, NDDSs have considerable potential for reshaping the polarization phenotype of microglia and could be a prospective therapeutic strategy for IS. The treatment of IS remains a challenge. However, this review provides a new perspective on neuro-nanomedicine for IS therapies centered on microglial polarization, thereby inspiring new research ideas and directions.

Targeted exosome-based nanoplatform for new-generation therapeutic strategies.

Exosomes, typically 30-150 nm in size, are lipid-bilayered small-membrane vesicles originating in endosomes. Exosome biogenesis is regulated by the coordination of various mechanisms whereby different cargoes (e.g. proteins, nucleic acids, and lipids) are sorted into exosomes. These components endow exosomes with bioregulatory functions related to signal transmission and intercellular communication. Exosomes exhibit substantial potential as drug-delivery nanoplatforms owing to their excellent biocompatibility and low immunogenicity. Proteins, miRNA, siRNA, mRNA, and drugs have been successfully loaded into exosomes, and these exosome-based delivery systems show satisfactory therapeutic effects in different disease models. To enable targeted drug delivery, genetic engineering and chemical modification of the lipid bilayer of exosomes are performed. Stimuli-responsive delivery nanoplatforms designed with appropriate modifications based on various stimuli allow precise control of on-demand drug delivery and can be utilized in clinical treatment. In this review, we summarize the general properties, isolation methods, characterization, biological functions, and the potential role of exosomes in therapeutic delivery systems. Moreover, the effective combination of the intrinsic advantages of exosomes and advanced bioengineering, materials science, and clinical translational technologies are required to accelerate the development of exosome-based delivery nanoplatforms.

Baseline Uric Acid Levels and Intravenous Thrombolysis Outcomes in Patients With Acute Ischemic Stroke: A Prospective Cohort Study.

BACKGROUND: The study aimed to investigate the relationship between uric acid (UA) levels and functional outcomes at 3 months in patients with acute ischemic stroke (AIS) who underwent intravenous thrombolysis (IVT). METHODS AND RESULTS: This prospective cohort study included 1001 consecutive patients with AIS who underwent IVT. The correlation between UA levels and post-IVT AIS outcomes was examined. Any nonlinear relationship was assessed using a restricted cubic spline function. The nonlinear P value for the association of UA levels with favorable (modified Rankin Scale [mRS] score ≤2) and excellent (mRS score ≤1) outcomes at 3 months post-IVT were <0.001 and 0.001, respectively. However, for patients with and without hyperuricemia, no evident nonlinear relationship was observed between UA levels and favorable 3-month post-IVT outcomes, with nonlinear P values of 0.299 and 0.207, respectively. The corresponding interaction analysis yielded a P value of 0.001, indicating significant heterogeneity. Similar results were obtained for excellent outcomes at 3 months post-IVT. In the hyperuricemia group, increased UA levels by 50 µmol/L reduced the odds of a favorable 3-month post-AIS outcome (odds ratio [OR], 0.75 [95% CI, 0.57-0.97]). Conversely, in the nonhyperuricemia group, a similar UA increase was linked to higher favorable outcome odds (OR, 1.31 [95% CI, 1.15-1.50]). CONCLUSIONS: An inverted U-shaped nonlinear relationship was observed between UA levels and favorable and excellent outcomes at 3 months in patients with AIS who underwent IVT. Higher UA levels predict favorable outcomes in patients without hyperuricemia but unfavorable outcomes in those with hyperuricemia.

Early tirofiban administration after intravenous thrombolysis in acute ischemic stroke (ADVENT): Study protocol of a multicenter, randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Nearly half of patients with acute ischemic stroke who undergo intravenous thrombolysis (IVT) fail to achieve excellent functional outcomes. Early administration of tirofiban after IVT may improve patient outcomes. OBJECTIVE: To evaluate the efficacy and safety of early tirofiban administration after intravenous tenecteplase in patients with acute ischemic stroke. METHODS AND DESIGN: The ADVENT trial is a multicenter, randomized, parallel-controlled, double-blind clinical trial. A total of 1084 patients undergoing IVT without subsequent endovascular treatment will be recruited from multiple hospitals in China. Subjects will be randomized in a 1:1 ratio to receive tirofiban or placebo, which will be infused within 6 h after IVT until 24 h after IVT, at 0.4 µg/kg/min for 30 min and then at 0.1 µg/kg/min. The primary efficacy outcome is the proportion of patients with excellent functional outcomes (modified Rankin Scale (mRS) ⩽ 1) at 90 days. Secondary outcomes include the proportion of patients with favorable functional outcomes (mRS ⩽ 2) at 90 days and neurological functional assessments evaluated during hospitalization. Symptomatic intracranial hemorrhage will be the primary safety outcome. Mortality and other adverse events will be recorded. DISCUSSION: This pivotal trial will provide important data on the early administration of antiplatelet therapy after IVT and may promote progress in treatment standards. TRIAL REGISTRY: ClinicalTrials.gov (NCT06045156).

Heart Rate Variability in Patients with Spontaneous Intracerebral Hemorrhage and its Relationship with Clinical Outcomes.

BACKGROUND: Although abnormal heart rate variability (HRV) is frequently observed in patients with spontaneous intracerebral hemorrhage (ICH), its time course and presentation of different indices remain unclear, and few studies have focused on its association with clinical outcomes. METHODS: We prospectively recruited consecutive patients with spontaneous ICH between June 2014 and June 2021. HRV was evaluated twice during hospitalization (within 7 days and 10-14 days after stroke). Time and frequency domain indices were calculated. A modified Rankin Scale score ≥ 3 at 3 months was defined as a poor outcome. RESULTS: Finally, 122 patients with ICH and 122 age- and sex-matched volunteers were included. Compared with controls, time domain and absolute frequency domain HRV parameters (total power, low frequency [LF], and high frequency [HF]) in the ICH group were significantly decreased within 7 days and 10-14 days. For relative values, normalized LF (LF%) and LF/HF were significantly higher, whereas normalized HF (HF%) was significantly lower, in the patient group than in the control group. Furthermore, LF% and HF% measured at 10-14 days were independently associated with 3-month outcomes. CONCLUSIONS: HRV values were impaired significantly within 14 days after ICH. Furthermore, HRV indices measured 10-14 days after ICH were independently associated with 3-month outcomes.

Serum Uric Acid Levels and Outcome of Acute Ischemic Stroke: a Dose-Response Meta-analysis.

Previous meta-analyses have reported conflicting results regarding the relationship between baseline uric acid (UA) levels and acute ischemic stroke (AIS) outcomes. Therefore, we conducted a dose-response meta-analysis to elucidate the association's strength and shape. Studies on the association between baseline UA levels and AIS outcomes in the PubMed and EMBASE databases were searched from their inception to April 17, 2023. Two researchers independently reviewed the studies for inclusion. A total of 23 articles involving 15,733 patients with AIS were included. The analysis revealed a significant inverse correlation between UA levels and AIS outcomes. The linear trend estimation indicated that a 50-µmol/L increment in UA level was associated with a 21.7% lower risk of hemorrhagic transformation (odds ratio [OR]: 0.783; 95% confidence interval [CI]: 0.743, 0.826; I2 = 43.4%; n = 4), 7.0% lower risk of 90-day unfavorable outcome [modified Rankin scale score ≥ 2] (OR: 0.930; 95% CI: 0.875, 0.990; I2 = 0%; n = 3), and 7.5% lower risk of 90-day poor outcome [modified Rankin scale score ≥ 3] (OR: 0.925; 95% CI: 0.863, 0.990; I2 = 74.4%; n = 3) in patients with AIS after accounting for relevant covariates. A linear dose-response relationship exists between baseline UA levels and the outcome of patients with AIS within a certain range, with higher baseline UA levels associated with better outcomes after AIS. Further dose-response meta-analyses, including a larger number of original articles, are required to validate our findings.

Safety and efficacy of remote ischemic conditioning for spontaneous intracerebral hemorrhage (SERIC-ICH): A multicenter, randomized, parallel-controlled clinical trial study design and protocol.

BACKGROUND: Previous studies have revealed that remote ischemic conditioning (RIC) may have a neuroprotective function. However, the potential benefit of RIC for patients with ICH remain unclear. OBJECTIVE: The primary aim of this study is to assess the safety and efficacy of RIC for patients with ICH. METHODS: The Safety and Efficacy of RIC for Spontaneous ICH (SERIC-ICH) is an ongoing prospective, randomized, multicenter, parallel-controlled, and blinded-endpoint clinical trial. The study will enroll an estimated 2000 patients aged ⩾18 years within 24 h after ICH onset, with National Institutes of Health Stroke Scale ⩾6 and Glasgow Coma Scale ⩾8 upon presentation. The patients will be randomly assigned to the RIC or control groups (1:1) and will be treated with cuffs inflated to a pressure of 200 or 60 mmHg, respectively, twice daily for 7 days. Each RIC treatment will consist of four cycles of arm ischemia for 5 min, followed by reperfusion for another 5 min, for a total procedure time of 35 min. The primary efficacy outcome measure is the proportion of patients with good functional outcomes (modified Rankin scale 0-2) at 180 days. The safety outcome measures will include all adverse events and severe adverse events occurring in the course of the study. DISCUSSION: RIC is an inexpensive intervention and might be a strategy to improve outcomes in patients with ICH. The SERIC-ICH trial will investigate whether RIC treatment can be applied as an adjuvant treatment in the acute phase of ICH and identify safety issues.

Levofloxacin alleviates blood-brain barrier disruption following cerebral ischemia and reperfusion via directly inhibiting A-FABP.

Reperfusion therapy is currently the most effective treatment for acute ischemic stroke, but often results in secondary brain injury. Adipocyte fatty acid-binding protein (A-FABP, FABP4, or aP2) was shown to critically mediate cerebral ischemia/reperfusion (I/R) injury by exacerbating blood-brain barrier (BBB) disruption. However, no A-FABP inhibitors have been approved for clinical use due to safety issues. Here, we identified the therapeutic effect of levofloxacin, a widely used antibiotic displaying A-FABP inhibitory activity in vitro, on cerebral I/R injury and determined its target specificity and action mechanism in vivo. Using molecular docking and site-directed mutagenesis, we showed that levofloxacin inhibited A-FABP activity through interacting with the amino acid residue Asp76, Gln95, Arg126 of A-FABP. Accordingly, levofloxacin significantly inhibited A-FABP-induced JNK phosphorylation and expressions of proinflammatory factors and matrix metalloproteinase 9 (MMP-9) in mouse primary macrophages. In wild-type mice with transient middle cerebral artery occlusion, levofloxacin substantially mitigated BBB disruption and neuroinflammation, leading to reduced cerebral infarction, alleviated neurological outcomes, and improved survival. Mechanistically, levofloxacin decreased MMP-9 expression and activity, and thus reduced degradation of extracellular matrix and endothelial tight junction proteins. Importantly, the BBB- and neuro-protective effects of levofloxacin were abolished in A-FABP or MMP-9 knockout mice, suggesting that the therapeutic effects of levofloxacin highly depended on specific targeting of the A-FABP-MMP-9 axis. Overall, our study demonstrates that levofloxacin alleviates A-FABP-induced BBB disruption and neural tissue injury following cerebral I/R, and unveils its therapeutic potential for the treatment of ischemic stroke.

Dynamic Cerebral Autoregulation After Carotid Endarterectomy.

OBJECTIVE: Studies have shown that dynamic cerebral autoregulation (dCA) is impaired in patients with severe internal carotid artery (ICA) stenosis and that carotid endarterectomy (CEA) may improve dCA in these patients. However, the time course of dCA changes in patients after CEA remains unclear. Therefore, this study aimed to investigate the effects of CEA on the dCA in patients with carotid artery stenosis at different time points. METHODS: This prospective study enrolled 44 patients (19 symptomatic stenosis patients and 25 asymptomatic stenosis patients) who underwent CEA and 44 age- and sex-matched controls. In the CEA group, the patients underwent dCA measurements at baseline, within 3 days, and 1 month after CEA. Transfer function parameters, phase difference (PD), and gain were used to quantify dCA. Changes in dCA before and after CEA were analyzed in detail. RESULTS: The bilateral PD of the patients before CEA was significantly lower than that of the control group. This damage did not improve within 3 days after surgery. One month after surgery, the PD on the affected side of the patients significantly improved compared with before surgery and reached the level of the control group. The PD of affected side across time points in symptomatic and asymptomatic stenosis patients is consistent with that in all patients. CONCLUSIONS: The dCA level did not improve immediately after CEA but significantly improved 1 month after surgery. This suggests that the occurrence of stroke should be considered in the acute period after CEA surgery, and its preventive effect on stroke may be effective after 1 month. CLINICAL IMPACT: We found the dCA level did not improve immediately after CEA but significantly improved 1 month after surgury. This suggests that the occuttencce of stroke and surgical complications (such as cerebral hyperperfusion syndrome) associated with impaired dCA in the acute phase after CEA surgery should be of particular concern.

Characteristics of Epicoccum latusicollum as revealed by genomic and metabolic phenomic analysis, the causal agent of tobacco Epicoccus leaf spot.

Epicoccum latusicollum is a fungus that causes a severe foliar disease on flue-cured tobacco in southwest China, resulting in significant losses in tobacco yield and quality. To better understand the organism, researchers investigated its optimal growth conditions and metabolic versatility using a combination of traditional methods and the Biolog Phenotype MicroArray technique. The study found that E. latusicollum exhibited impressive metabolic versatility, being able to metabolize a majority of carbon, nitrogen, sulfur, and phosphorus sources tested, as well as adapt to different environmental conditions, including broad pH ranges and various osmolytes. The optimal medium for mycelial growth was alkyl ester agar medium, while oatmeal agar medium was optimal for sporulation, and the optimum temperature for mycelial growth was 25°C. The lethal temperature was 40°C. The study also identified arbutin and amygdalin as optimal carbon sources and Ala-Asp and Ala-Glu as optimal nitrogen sources for E. latusicollum. Furthermore, the genome of E. latusicollum strain T41 was sequenced using Illumina HiSeq and Pacific Biosciences technologies, with 10,821 genes predicted using Nonredundant, Gene Ontology, Clusters of Orthologous Groups, Kyoto Encyclopedia of Genes and Genomes, and SWISS-PROT databases. Analysis of the metabolic functions of phyllosphere microorganisms on diseased tobacco leaves affected by E. latusicollum using the Biolog Eco microplate revealed an inability to efficiently metabolize a total of 29 carbon sources, with only tween 40 showing some metabolizing ability. The study provides new insights into the structure and function of phyllosphere microbiota and highlights important challenges for future research, as well as a theoretical basis for the integrated control and breeding for disease resistance of tobacco Epicoccus leaf spot. This information can be useful in developing new strategies for disease control and management, as well as enhancing crop productivity and quality.

Remote ischemic conditioning attenuates oxidative stress and inflammation via the Nrf2/HO-1 pathway in MCAO mice.

The protective effects of remote ischemic conditioning (RIC) on acute ischemic stroke have been reported. However, the protective mechanisms of RIC have not been fully elucidated. This study aimed to investigate whether RIC could reduce oxidative stress and inflammatory responses in middle cerebral artery occlusion (MCAO)-reperfusion mice via the nuclear factor-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. C57BL/6 mice were subjected to MCAO and underwent RIC twice daily at 1, 3, and 7 days after MCAO. ML385 was used to specifically inhibit Nrf2 in MCAO mice. Neurological deficit scores, infarct volume, and hematoxylin-eosin (HE) staining were assessed. Oxidative stress levels were assessed based on total antioxidant capacity (TAC), malonaldehyde (MDA), superoxide dismutase (SOD), and glutathione/glutathione disulfide (GSH/GSSG). mRNA levels were detected using real-time polymerase chain reaction (PCR), and protein levels were detected using western blotting and enzyme-linked immunosorbent assay (ELISA). Protein localization was investigated using immunofluorescence staining. RIC significantly reduced infarct volume and improved neurological function and histological changes after MCAO. RIC significantly increased TAC, SOD, and GSH/GSSG levels and decreased MDA levels. RIC significantly increased Nrf2 and HO-1 mRNA levels and decreased Keap1, NLRP3, and Cleaved Caspase-1 mRNA levels. RIC significantly increased Nrf2, HO-1, and NQO1 protein expression and decreased Keap1, NLRP3, Cleaved Caspase-1, Cleaved IL-1ß, IL-6, and TNF-α protein expression. RIC promoted the activation and translocation of Nrf2 into the nucleus. The protective effects of RIC were abolished by ML385 treatment. In conclusion, our findings suggest that RIC alleviates oxidative stress and inflammatory responses via the Nrf2/HO-1 pathway, which in turn improves neurobehavioral function. RIC may provide novel therapeutic options for acute ischemic stroke.

Gut microbiota-derived metabolite trimethylamine-N-oxide and stroke outcome: a systematic review.

Introduction: The relationship between baseline trimethylamine N-oxide (TMAO) levels and stroke outcomes remains unclear. Therefore, this systematic review aimed to summarize the existing relevant research. Methods: We searched for studies on the association between baseline plasma levels of TMAO and stroke outcomes in the PubMed, EMBASE, Web of Science, and Scopus databases from their inception to 12 October 2022. Two researchers independently reviewed the studies for inclusion and extracted the relevant data. Results: Seven studies were included in the qualitative analysis. Among them, six studies reported the outcome of acute ischemic stroke (AIS) and one study of intracerebral hemorrhage (ICH), respectively. Furthermore, no study reported the outcome of subarachnoid hemorrhage. Among patients with AIS, high baseline TMAO levels were associated with unfavorable functional outcomes or mortality at 3 months, as well as a high hazard ratio of mortality, recurrence, or major adverse cardiac event. Moreover, TMAO levels showed predictive utility for unfavorable functional outcomes or mortality at 3 months. Among patients with ICH, high TMAO levels were associated with unfavorable functional outcomes at 3 months, regardless of whether the TMAO value was considered a continuous or a categorical variable. Conclusion: Limited evidence indicates that high baseline plasma levels of TMAO may be associated with poor stroke outcomes. Further studies are warranted to confirm the relationship between TMAO and stroke outcomes.

Changes in cerebral autoregulation, stroke-related blood biomarkers, and autonomic regulation after patent foramen ovale closure in severe migraine patients.

AIMS: This study aimed to investigate changes in dynamic cerebral autoregulation (dCA), 20 stroke-related blood biomarkers, and autonomic regulation after patent foramen ovale (PFO) closure in severe migraine patients. METHODS: Patent foramen ovale severe migraine patients, matched non-PFO severe migraine patients, and healthy controls were included. dCA and autonomic regulation were evaluated in each participant at baseline, and within 48-h and 30 days after closure in PFO migraineurs. A panel of stroke-related blood biomarkers was detected pre-surgically in arterial-and venous blood, and post-surgically in the arterial blood in PFO migraineurs. RESULTS: Forty-five PFO severe migraine patients, 50 non-PFO severe migraine patients, and 50 controls were enrolled. The baseline dCA function of PFO migraineurs was significantly lower than that of non-PFO migraineurs and controls but was rapidly improved with PFO closure, remaining stable at 1-month follow-up. Arterial blood platelet-derived growth factor-BB (PDGF-BB) levels were higher in PFO migraineurs than in controls, which was immediately and significantly reduced after closure. No differences in autonomic regulation were observed among the three groups. CONCLUSION: Patent foramen ovale closure can improve dCA and alter elevated arterial PDGF-BB levels in migraine patients with PFO, both of which may be related to the preventive effect of PFO closure on stroke occurrence/recurrence.

Heart Rate Variability Parameter Changes in Patients With Acute Ischemic Stroke Undergoing Intravenous Thrombolysis.

Background Autonomic dysfunction has been revealed in patients with acute ischemic stroke and is associated with poor prognosis. However, autonomic nervous system function assessed by heart rate variability (HRV) and its relationship with clinical outcomes in patients undergoing intravenous thrombolysis (IVT) remain unknown. Methods and Results Patients who did and did not undergo IVT between September 2016 and August 2021 were prospectively and consecutively recruited. HRV values were measured at 1 to 3 and 7 to 10 days after stroke to assess autonomic nervous system function. A modified Rankin scale score ≥2 at 90 days was defined as an unfavorable outcome. Finally, the analysis included 466 patients; 224 underwent IVT (48.1%), and 242 did not (51.9%). Linear regression showed a positive correlation of IVT with parasympathetic activation-related HRV parameters at 1 to 3 days (high frequency: ß=0.213, P=0.002) and with both sympathetic (low frequency: ß=0.152, P=0.015) and parasympathetic activation-related HRV parameters (high frequency: ß=0.153, P=0.036) at 7 to 10 days after stroke. Logistic regression showed HRV values and autonomic function within 1 to 3 and 7 to 10 days after stroke were independently associated with 3-month unfavorable outcomes after adjusting for confounders in patients who underwent IVT (all P<0.05). Furthermore, addition of HRV parameters to conventional risk factors significantly improved risk-predictive ability of 3-month outcome (the area under the receiver operating characteristic curve significantly improved from 0.784 [0.723-0.846] to 0.855 [0.805-0.906], P=0.002). Conclusions IVT positively affected HRV and autonomic nervous system activity, and autonomic function assessed by HRV in acute stroke phase was independently associated with unfavorable outcomes in patients undergoing IVT.