PURPOSE:This study aimed to investigate the association of the neutrophil to high-density lipoprotein ratio (NHR) with disease severity and short-term prognosis at discharge in anti-N-methyl-D-aspartic acid receptor (NMDAR) encephalitis patients. PATIENTS AND METHODS:A retrospective study enrolled 186 patients with anti-NMDAR encephalitis, who were stratified by mRS and CASE to identify independent influencing factors for disease severity and short-term prognosis at discharge. Multivariate regression models including these independent influencing factors were established to assess disease severity and predict short-term prognosis at discharge. Receiver operating characteristic curves, bootstrap, concordance index, calibration curves, and Hosmer-Lemeshow goodness-of-fit test were used to evaluate the generalization ability of these models. The train set, test set, and validation set were used to verify the generalization ability of these models. Spearman's correlation analysis was applied to investigate the correlation between CASE and mRS. RESULTS:Anti-NMDAR encephalitis patients were assessed by mRS and CASE, and were grouped separately. Both results indicated that NHR was a predictor of disease severity and short-term prognosis. The regression models established based on NHR and other independent influencing factors exhibited good discrimination, accuracy, and generalization ability in disease severity assessment and short-term prognosis prediction. Statistical analysis demonstrated that CASE was positively correlated with mRS. CONCLUSION:NHR had potential clinical value in the assessment of disease severity at admission and prediction of short-term prognosis at discharge in anti-NMDAR encephalitis patients. CASE, a dedicated scale for autoimmune encephalitis, was positively correlated with mRS.
Background: Cognitive impairment is a common concern among individuals with heart failure, and the intersection of these conditions poses significant challenges for scholarly investigation. This study aims to conduct a comprehensive bibliometric analysis to visually depict the current state and emerging trends regarding cognitive impairment among heart failure patients. Methods: Articles focusing on cognitive impairment in heart failure patients published between 2013 and 2022 were retrieved from the Web of Science Core Collection on February 3, 2023. Analysis of publication trends was conducted using Microsoft Excel 2016. The bibliometric analysis,involving identification of the leading countries, institutions, and authors, as well as the analysis of keywords co-occurrence and burst-detection, was performed using CiteSpace and VOSviewer. Results: A total of 260 original articles were included. The data showed a stable pattern of annual publications on cognitive impairment in heart failure patients over the last ten years. The United States stood out with 129 publications, Kent State University in the USA led in institutional output with 32 articles, and Gunstad John was identified as the most influential author with 32 articles and 572 citations. Analysis of keyword co-occurrence network revealed core research themes encompassing risk factors, interventions, assessment, and underlying mechanisms of cognitive impairment in heart failure patients. Conclusions: This study presents the first bibliometric analysis of research on cognitive impairment in heart failure patients over the past decade, offering valuable insights for exploring future research frontiers in this domain. The findings provide researchers, clinicians, and policymakers with key information to advance understanding and interventions for cognitive impairment in heart failure patients.
Gastrointestinal stromal tumors (GISTs) predominantly develop in the stomach. While nomogram offer tremendous therapeutic promise, there is yet no ideal nomogram comparison customized specifically for handling categorical data and model selection related gastric GISTs. (1) We selected 5463 patients with gastric GISTs from the SEER Research Plus database spanning from 2000 to 2020; (2) We proposed an advanced missing data imputation algorithm specifically designed for categorical variables; (3) We constructed five Cox nomogram models, each employing distinct methods for the selection and modeling of categorical variables, including Cox (Two-Stage), Lasso-Cox, Ridge-Cox, Elastic Net-Cox, and Cox With Lasso; (4) We conducted a comprehensive comparison of both overall survival (OS) and cancer-specific survival (CSS) tasks at six different time points; (5) To ensure robustness, we performed 50 randomized splits for each task, maintaining a 7:3 ratio between the training and test cohorts with no discernible statistical differences. Among the five models, the Cox (Two-Stage) nomogram contains the fewest features. Notably, at Near-term, Mid-term, and Long-term intervals, the Cox (Two-Stage) model attains the highest Area Under the Curve (AUC), top-1 ratio, and top-3 ratio in both OS and CSS tasks. For the prediction of survival in patients with gastric GISTs, the Cox (Two-Stage) nomogram stands as a simple, stable, and accurate predictive model with substantial promise for clinical application. To enhance the clinical utility and accessibility of our findings, we have deployed the nomogram model online, allowing healthcare professionals and researchers worldwide to access and utilize this predictive tool.
Paraneoplastic neurological syndrome refers to certain malignant tumors that have affected the distant nervous system and caused corresponding dysfunction in the absence of tumor metastasis. Patients with this syndrome produce multiple antibodies, each targeting a different antigen and causing different symptoms and signs. The CV2/collapsin response mediator protein 5 (CRMP5) antibody is a major antibody of this type. It damages the nervous system, which often manifests as limbic encephalitis, chorea, ocular manifestation, cerebellar ataxia, myelopathy, and peripheral neuropathy. Detecting CV2/CRMP5 antibody is crucial for the clinical diagnosis of paraneoplastic neurological syndrome, and anti-tumor and immunological therapies can help to alleviate symptoms and improve prognosis. However, because of the low incidence of this disease, few reports and no reviews have been published about it so far. This article intends to review the research on CV2/CRMP5 antibody-associated paraneoplastic neurological syndrome and summarize its clinical features to help clinicians comprehensively understand the disease. Additionally, this review discusses the current challenges that this disease poses, and the application prospects of new detection and diagnostic techniques in the field of paraneoplastic neurological syndrome, including CV2/CRMP5-associated paraneoplastic neurological syndrome, in recent years.
Objective: This study aimed to analyze the microstructural features of sleep in patients with vestibular migraine and migraine, and to hypothesize the pathophysiological mechanism between vestibular migraine and sleep disorders.Methods: From March 2021 to June 2022, 35 vestibular migraine patients, 35 migraine patients, and 30 controls were collected from the Vertigo Center & Sleep Center of the Second Affiliated Hospital of Zhengzhou University. The anxiety and depression status, sleep quality, and cyclic alternating pattern (CAP) of the three groups were analyzed and compared using the Pittsburgh Sleep Quality Index, Hamilton Anxiety and Depression Scale, and polysomnography (PSG).Results: The vestibular migraine group had a higher CAP time (mean 173.64 vs. 122.11, P < 0.001), CAP index (mean 54.25 vs. 37.50, P < 0.001), CAP rate (mean 48.41 vs. 32.31, P < 0.001), CAP sequences (mean 42.60 vs. 29.83, P < 0.001), A3% (mean 45.58 vs. 17.50, P < 0.001) and A2% thorn A3% (mean 68.87 vs. 38.83, P < 0.001) compared to the control group, with a lower A1 index (mean 16.68 vs. 23.87, P < 0.001) and A1% (mean 31.13% vs. 61.17, P < 0.001).Conclusion: Patients with vestibular migraine have poor sleep quality, thalamic-cortical hyperfunction and active arousal system. In addition, high CAP rate and high A2 to A3 ratio make the sleep structure more fragmented.(c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Background Glibenclamide is a promising agent for treating brain oedema, but whether it improves clinical outcomes in patients with intracerebral haemorrhage (ICH) remains unclear. In this study, we aimed to explore the efficacy and safety of glibenclamide treatment in patients with acute ICH. Methods The Glibenclamide Advantage in Treating Oedema after Intracerebral Haemorrhage (GATE-ICH) study was a randomised controlled phase 2 clinical trial conducted in 26 hospitals in the northwest of China, recruiting patients with acute ganglia ICH no more than 72 h after onset from Dec 12, 2018 to Sept 23, 2020. During the first 7 days after enrolment, patients randomly assigned to the glibenclamide group were given glibenclamide orally (1.25 mg, 3/day) and standard care, while patients randomly assigned to the control group were given standard care alone. The computer-generated randomisation sequence was prepared by a statistician not involved in the rest of the study. Randomisation was computer-generated with a block size of four. The allocation results were unblinded to participants and investigators. The primary outcome was the percentage of patients with poor outcome (defined as modified Rankin Scale [mRS] score of >= 3) at day 90. The trial was registered at ClinicalTrials.gov (NCT03741530). Findings 220 participants were randomised and 200 participants (mean [standard deviation] age, 56 [11] years; sex, 128 [64.0%] male and 72 [36.0%] female) were included in the final analysis, with 101 participants randomly assigned to the control group and 99 to the glibenclamide group. The incidence of poor outcome at day 90 was 20/ 99 (20.2%) in glibenclamide group and 30/101 (29.7%) in control group (absolute difference, 9.5%; 95% confidence interval [CI], -3.2%-21.8%; P = 0.121) with adjusted odds ratios of 0.54 (95% CI, 0.24-1.20; P = 0.129). No significant difference was found in the overall rates of adverse events or serious adverse events between groups. However, the incidence of asymptomatic hypoglycaemia was significantly higher in glibenclamide group than control group (15/99 [15.2%] vs 0/101 [0.0%]; absolute difference, 15.2%; 95% CI, 7.5%-24.1%; P < 0.001). Interpretation Our study provides no evidence that glibenclamide (1.25 mg, 3/day) significantly reduces the proportion of poor outcome at day 90 after ICH. In addition, glibenclamide could result in higher incidence of hypoglycaemia. Larger trials of glibenclamide with optimised medication regimen are warranted. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.
Clinically, physicians collect the benchmark medical data to establish archives for a stroke patient and then add the follow up data regularly. It has great significance on prognosis prediction for stroke patients. In this paper, we present an interpretable deep learning model to predict the one-year mortality risk on stroke. We design sub-modules to reconstruct features from original clinical data that highlight the dissimilarity and temporality of different variables. The model consists of Bidirectional Long Short-Term Memory (Bi-LSTM), in which a novel correlation attention module is proposed that takes the correlation of variables into consideration. In experiments, datasets are collected clinically from the department of neurology in a local AAA hospital. It consists of 2,275 stroke patients hospitalized in the department of neurology from 2014 to 2016. Our model achieves a precision of 0.9414, a recall of 0.9502 and an F1-score of 0.9415. In addition, we provide the analysis of the interpretability by visualizations with reference to clinical professional guidelines.
PURPOSE:There is increasing evidence of a causal interaction between obstructive sleep apnea (OSA) and white matter hyperintensity (WMH). WMH and enlarged perivascular space (EPVS) are the neuroimaging markers for cerebral small vessel disease (CSVD). Thus, this study aimed to determine whether a contextual relationship existed between OSA and EPVS.PARTICIPANTS AND METHODS:In this study, 107 participants underwent 1-night polysomnography, brain magnetic resonance imaging (MRI) and health screening examinations and were classified as 63 OSA patients (mild, moderate, and severe groups), and 44 healthy controls. We assessed the sleep characteristics in OSA group, quantified the total EPVS from MRI and related them to the measures of polysomnography-obtained sleep parameters.RESULTS:Polysomnography revealed that 63 OSA patients had sleep architecture alteration. A higher proportion of N2 phase sleep (N2%), lower percentage of N3 sleep (N3%) and REM sleep (REM%), as well as increased arousal index (AI), oxygen desaturation index (ODI) and decreased lowest arterial oxygen saturation (LSaO2) were detected. The results also indicated a higher prevalence and a larger number of EPVS, and a lower Mini Mental State Scale (MMSE) scale score in OSA group. LSaO2, N3% and REM% were negatively correlated with the total EPVS, whereas ODI, AI and N2% were positively correlated with the total EPVS.CONCLUSION:The findings suggested that OSA patients had sleep disturbances with a higher incidence and more severe EPVS. Furthermore, the EPVS in OSA might be secondary to sleep disturbances, intermittent hypoxemia and the respiratory event-related hemodynamic changes. Thus, our findings highlighted that increased risk for EPVS in OSA is a potential contributor to increased stroke risk in OSA.
Analyzing sleep quality and sleep structure in patients with patent foramen ovale (PFO) complicated with obstructive sleep apnea (OSA) and the interaction between OSA and PFO in sleep. We compared patients with PFO complicated with OSA, patients with simple PFO, and controls. Pittsburgh Sleep Quality Index was used to compare sleep quality and polysomnography was used to compare sleep structure of the three groups. Compared with the control group (n = 62), PFO with OSA (n = 48) and simple PFO (n = 61) groups had more frequent occurrence of poor sleep quality (χ2 = 89.901; p < 0.001). These two groups also showed decreased sleep efficiency (p < 0.010), lower percentages of REM sleep, and reduced N3 sleep (p < 0.050). The N2 sleep was prolonged (p < 0.010). The nocturnal lowest SpO2 was lower and the oxygen desaturation index was higher (p < 0.50). Compared with the simple PFO group, the poor sleep quality was more frequent in the PFO with OSA group; sleep latency (p < 0.001) was prolonged; wake after sleep onset (p < 0.001) and arousal times (p = 0.031) were increased; and sleep micro-arousal index (p = 0.037), periodic leg movement index (p = 0.024), and apnea hypopnea index (p < 0.001) were higher in the PFO with OSA group. Patients with PFO and OSA have poor sleep quality with changes in sleep stage and high occurrence rate of sleep disorders. OSA further deteriorates sleep quality and alters sleep structure in patients with PFO.
Metabolic waste clearance is essential to maintain body homeostasis, in which the lymphatic system plays a vital role. Conversely, in recent years, studies have identified the glial–lymphatic system in the brain, which primarily comprises the inflow of fluid along the para-arterial space. Aquaporin-4 mediates the convection of interstitial fluid in the brain and outflow along the paravenous space. β-Amyloid deposition is a characteristic pathological change in Alzheimer’s disease, and some studies have found that the glial–lymphatic system plays an important role in its clearance. Thus, the glial–lymphatic system may influence Alzheimer’s disease severity and outcome; therefore, this review summarizes the current and available research on the glial–lymphatic system and Alzheimer’s disease.
Microglia are rapidly activated after acute ischemic stroke, and the polarization of microglial is associated with the prognosis of acute ischemic stroke. Lipoxin A4 (LXA4), an anti-inflammatory agent, has a protective effect against ischemic stroke. However, the role of LXA4 on the polarization of microglial after acute ischemic stroke remains undetermined. We hypothesized that LXA4 may exert the neuroprotective effect though regulating the polarization of microglial. In this study, clinical features of acute ischemic stroke were simulated using a rat model of model of middle cerebral artery occlusion (MCAO) in vivo and the BV2 microglia oxygen-glucose deprivation/reoxygenation model (OGD/R) in vitro. The protective effects of LXA4 on cerebral ischemia-reperfusion injury were determined using TTC staining, HE staining, and TUNEL staining. The expression of targeted genes was assayed using quantitative real-time PCR (qRT-PCR), immunofluorescence, and western blot to investigated the regulation of LXA4 on microglia polarization after acute ischemic stroke. We found that LXA4 exerted protective effects on focal cerebral ischemia-reperfusion injury and reduced the expression of the pro-inflammatory cytokines IL-1β and TNF-α. Furthermore, LXA4 inhibited the expression of Notch-1, Hes1, iNOS and CD32 all of which are associated with the differentiation into M1 microglia. By contrast, LXA4 upregulated the expression of Hes5, Arg-1 and CD206 all of which are associated with M2 phenotype in microglia. In addition, blocking the Notch signaling pathway with the inhibitor DAPT significantly mitigated the effect of LXA4 on microglia differentiation. These data suggest that LXA4 may regulate the polarization of microglia after cerebral ischemia-reperfusion injury through the Notch signaling pathway.
Objectives: Autonomic dysfunction is a common symptom of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis; however, it has been poorly researched. The purpose of this study was to compare the clinical features, tumor occurrence, intensive care unit (ICU) admission, mechanical ventilation, imaging assessment, cerebrospinal fluid examination, disease severity, and immunotherapy in patients with anti-NMDAR encephalitis with or without autonomic dysfunction.Methods: A retrospective study of anti-NMDAR encephalitis patients diagnosed between January 2016 and April 2020 was performed at the First Affiliated Hospital of Zhengzhou University. Patients were divided into two groups according to whether they had autonomic dysfunction, and their clinical features, treatment, and prognosis were compared.Results: A total of 119 patients with anti-NMDAR encephalitis were included in this study. Seventy-three patients (61.3%) had autonomic dysfunction, while the remaining 46 (38.7%) did not. Sinus tachycardia (69.9%) was the autonomic dysfunction with the highest incidence, while the incidences of symptoms including constipation, central hypopnea, and others gradually decreased. Compared to the group without autonomic dysfunction, the prevalence of the main clinical symptoms such as epileptic seizure (P = 0.003), involuntary movement (P = 0.028), and decreased consciousness (P < 0.001) were higher in the group with autonomic dysfunction, which also more frequently presented with complications such as pulmonary infection (P < 0.001) and abnormal liver function (P = 0.001). Moreover, the rates of ICU admission (P < 0.001) and mechanical ventilation (P = 0.001), as well as the modified Rankin scale (mRS) scores at admission (P < 0.001), maximum mRS scores during the course of disease (P < 0.001), and mRS scores at discharge (P < 0.001) were higher in the patients with autonomic dysfunction than in those without. The number of patients in the autonomic dysfunction group who underwent ≥2 immunotherapies was also higher than that in the group without autonomic dysfunction (P < 0.001).Conclusion: Sinus tachycardia is the most common type of autonomic dysfunction in anti-NMDAR encephalitis. Compared to patients without autonomic dysfunction, those with autonomic dysfunction had a higher incidence of epilepsy, involuntary movements, decreased consciousness, pulmonary infections, abnormal liver function, ICU admissions, and mechanical ventilation; moreover, the severity of the disease was greater, and their prognosis worse. Therefore, such patients require intensive immunotherapy.
We aimed to study the clinical characteristics and biological indicators of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis with different severity levels to explore factors predicting disease severity at admission. Using the modified Rankin scale (mRS), patients were divided into mild-to-moderate group (mRS ≤ 3) and severe group (mRS > 3) on admission based on severity of illness. General information, previous history, premonitory symptoms, clinical manifestations before admission, imaging findings and biochemical tests were compared to explore the clinical manifestations and biological indicators related to the severity of illness at admission. In the severe group, the incidences of fever, anti-infective therapy, generalized seizures, consciousness disorder, blood white blood cell, neutrophils, and neutrophil–lymphocyte ratio (NLR) were higher than those in mild-to-moderate group (P < 0.001, P = 0.001, P = 0.020, P < 0.001, P = 0.002, P < 0.001, P < 0.001, respectively); blood lymphocyte counts was lower than those in mild-to-moderate group (P < 0.001). There was the strongest significant positive correlation between the NLR and disease severity at admission (rs = 0.684, P < 0.001). In multivariate logistic regression, fever, generalized seizures, consciousness disorder, and elevated NLR were independent risk factors for disease severity; the area under the receiver operating characteristic curve was 0.896 (95%CI: 0.840–0.952, P < 0.001). Fever, generalized seizures, consciousness disorder, and elevated NLR were independent risk factors for disease severity. NLR is a good predictor of the severity of illness at admission.
Metabolic waste clearance is essential to maintain body homeostasis, in which the lymphatic system plays a vital role. Conversely, in recent years, studies have identified the glial-lymphatic system in the brain, which primarily comprises the inflow of fluid along the para-arterial space. Aquaporin-4 mediates the convection of interstitial fluid in the brain and outflow along the paravenous space. beta-Amyloid deposition is a characteristic pathological change in Alzheimer's disease, and some studies have found that the gliallymphatic system plays an important role in its clearance. Thus, the glial-lymphatic system may influence Alzheimer's disease severity and outcome; therefore, this review summarizes the current and available research on the glial-lymphatic system and Alzheimer's disease.
Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, 450000, People’s Republic of China Purpose: There is increasing evidence of a causal interaction between obstructive sleep apnea (OSA) and white matter hyperintensity (WMH). WMH and enlarged perivascular space (EPVS) are the neuroimaging markers for cerebral small vessel disease (CSVD). Thus, this study aimed to determine whether a contextual relationship existed between OSA and EPVS. Participants and Methods: In this study, 107 participants underwent 1-night polysomnography, brain magnetic resonance imaging (MRI) and health screening examinations and were classified as 63 OSA patients (mild, moderate, and severe groups), and 44 healthy controls. We assessed the sleep characteristics in OSA group, quantified the total EPVS from MRI and related them to the measures of polysomnography-obtained sleep parameters. Results: Polysomnography revealed that 63 OSA patients had sleep architecture alteration. A higher proportion of N2 phase sleep (N2%), lower percentage of N3 sleep (N3%) and REM sleep (REM%), as well as increased arousal index (AI), oxygen desaturation index (ODI) and decreased lowest arterial oxygen saturation (LSaO2) were detected. The results also indicated a higher prevalence and a larger number of EPVS, and a lower Mini Mental State Scale (MMSE) scale score in OSA group. LSaO2, N3% and REM% were negatively correlated with the total EPVS, whereas ODI, AI and N2% were positively correlated with the total EPVS. Conclusion: The findings suggested that OSA patients had sleep disturbances with a higher incidence and more severe EPVS. Furthermore, the EPVS in OSA might be secondary to sleep disturbances, intermittent hypoxemia and the respiratory event-related hemodynamic changes. Thus, our findings highlighted that increased risk for EPVS in OSA is a potential contributor to increased stroke risk in OSA.
Background: This study aimed to evaluate the prevalence of restless legs syndrome (RLS) in patients with migraine and explore its association with vitamin D deficiency, aiming to provide biological support for the comorbidity of migraine with RLS, and shed new lights into clinical diagnosis and treatment. Methods: A case-control study was performed on 175 migraine patients and 151 non-headache controls. The information of all subjects concerning headache severity [visual analog scale (VAS) score], RLS, RLS severity [International Restless Legs Scale (IRLS) score], sleep quality [Pittsburgh sleep quality index (PSQI)], anxiety and depression symptoms [hospital anxiety and depression scale (HADS)], and demographic data were collected. At the same time, serum 25-(OH) D levels were also measured (concentration <20 ng/ml was defined deficiency). Afterward, the logistic regression model was adopted to explore the risk factors for RLS in patients with migraines. Results: Compared with control group, migraine group had lower vitamin D levels [(21.10 ± 6.58) vs. (16.42 ± 5.6) ng/ml, P < 0.001], a higher rate of vitamin D deficiency (45.03 vs. 72%, P <0001), higher prevalence of RLS (6.62 vs. 22.29%, P < 0.001). Compared with the pure RLS group, RLS with the migraine group had lower vitamin D levels and higher IRLS score (P < 0.05). Compared with pure migraine group, migraine with RLS group had lower vitamin D levels [(17.36 ± 5.56) vs. (13.15 ± 4.42) ng/ml, P < 0.001], higher incidence of vitamin D deficiency (66.18 vs. 92.31%, P = 0.001), higher frequency of headache attacks (P = 0.004). Thereafter, the multivariate logistic regression model was employed to adjust confounding factors such as age, gender, season, frequency of headache attacks, PSQI score, and HADS scores. According to the results vitamin D deficiency in patients with migraines was an independent risk factor for RLS (OR = 5.03, 95%CI: 1.2–21.16, P = 0.027). Conclusions: The prevalence of RLS in migraine patients was significantly higher than that in the non-headache population. Besides, vitamin D levels decreased, while the incidence of vitamin D deficiency increased in the migraine patients complicated with RLS. Finally, the occurrence of RLS in migraine patients was significantly related to vitamin D deficiency.
To study and analyze the sleep quality and sleep structure of patients with vestibular migraine (VM). In this cross-sectional case-control study, the Pittsburgh Sleep Quality Index (PSQI) questionnaire and polysomnography (PSG) were used to compare the clinical characteristics of sleep disorders in 49 patients with VM, 52 patients with migraine, and 54 controls. The VM, migraine, and control groups did not significantly differ in terms of age or sex. Compared with the migraine and control groups, the VM group had a higher incidence of poor sleep quality (χ2 = 36.618, p < 0.01) and greater severity of poor sleep quality (p < 0.01). Furthermore, the VM group showed reduced sleep efficiency (p < 0.01) and reduced proportions of REM and slow wave (N3) sleep (p ≤ 0.01). Conversely, sleep latency (p = 0.01) and REM latency (p = 0.04) were prolonged, and proportions of light sleep phases (N1, p < 0.05, and N2, p < 0.01) and the micro-arousal index (p = 0.03) were increased. The migraine group had significantly higher apnea hypopnea (AHI) and periodic leg movement (PLMI) indices than the VM group. We report an effect of VM on sleep structure and an association with migraine. Similar to migraine, VM affects the sleep regulation centers and causes structural sleep disorders.
Aquaporin (AQP4) could be associated with inflammation, common in central nervous system diseases. We investigated the effect of lipoxin A4 (LXA4) on the activation of astrocytes, AQP4 expression, and inflammatory response induced by lipopolysaccharide (LPS). Astrocytes were cultured in vitro and changes in transcript and protein levels of AQP4, interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and cyclooxygenase-2 (COX-2), and protein levels of P38 and phospho-P38 were determined. The LPS group showed increased AQP4, IL-1β, TNF-α, and COX-2 levels, whereas they decreased in the LPS + LXA4 group, suggesting that LXA4 inhibits AQP4 expression. Furthermore, levels of phospho-P38 increased in the LPS group, but decreased in the LPS + LXA4 group. In conclusion, LXA4 alleviated the LPS-induced increase in AQP4 expression and inflammatory cytokine secretion by astrocytes, possibly by inhibiting P38 phosphorylation. For the first time, we found that LXA4 may inhibit the expression of inflammatory factors by regulating the expression of AQP4. AQP4 on astrocytes is likely to be the target of anti-inflammatory effect of LXA4.
Intracerebral hemorrhage (ICH) is a fatal acute cerebrovascular disease, with a high morbidity and mortality. Following ICH, erythrocytes release heme and several of its metabolites, thereby contributing to brain edema and secondary brain damage. Heme oxygenase is the initial and rate-limiting enzyme of heme catabolism, and the expression of heme oxygenase-1 (HO-1) is rapidly induced following acute brain injury. As HO-1 exerts it effects via various metabolites, its role during ICH remains complex. Therefore, in-depth studies regarding the role of HO-1 in secondary brain damage following ICH may provide a theoretical basis for neuroprotective function after ICH. The present review aims to summarize recent key studies regarding the effects of HO-1 following ICH, as well as its influence on ICH prognosis.