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BackgroundPreserving the integrity of the blood-brain barrier (BBB) is beneficial to avoid further brain damage after acute ischemic stroke (AIS). Astrocytes, an important component of the BBB, promote BBB breakdown in subjects with AIS by secreting inflammatory factors. The glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 (Ex-4) protects the BBB and reduces brain inflammation from cerebral ischemia, and GLP-1R is expressed on astrocytes. However, the effect of Ex-4 on astrocytes in subjects with AIS remains unclear.MethodsIn the present study, we investigated the effect of Ex-4 on astrocytes cultured under oxygen-glucose deprivation (OGD) plus reoxygenation conditions and determined whether the effect influences bEnd.3 cells. We used various methods, including permeability assays, western blotting, immunofluorescence staining, and gelatin zymography, in vitro and in vivo.ResultsEx-4 reduced OGD-induced astrocyte-derived vascular endothelial growth factor (VEGF-A), matrix metalloproteinase-9 (MMP-9), chemokine monocyte chemoattractant protein-1 (MCP-1), and chemokine C-X-C motif ligand 1 (CXCL-1). The reduction in astrocyte-derived VEGF-A and MMP-9 was related to the increased expression of tight junction proteins (TJPs) in bEnd.3 cells. Ex-4 improved neurologic deficit scores, reduced the infarct area, and ameliorated BBB breakdown as well as decreased astrocyte-derived VEGF-A, MMP-9, CXCL-1, and MCP-1 levels in ischemic brain tissues from rats subjected to middle cerebral artery occlusion. Ex-4 reduced the activation of the JAK2/STAT3 signaling pathway in astrocytes following OGD.ConclusionBased on these findings, ischemia-induced inflammation and BBB breakdown can be improved by Ex-4 through an astrocyte-dependent manner.

BackgroundBrain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and multiple sclerosis (MS).ObjectivesTo investigate comparative brain stem lesions on magnetic resonance imaging (MRI) among adult patients with ADEM, NMO, and MS.MethodsSixty-five adult patients with ADEM (n = 17), NMO (n = 23), and MS (n = 25) who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed.ResultsPatients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001) and MS (94.1% vs. 40.0%, P<0.001); patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001) and ADEM (34.8% vs. 70.6%, P = 0.025); and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001) and MS (91.3% vs. 36.0%, P<0.001). On the axial section of the brain stem, the majority (82.4%) of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%); and lesions in patients with MS were found in both the ventral (44.0%) and dorsal (56.0%) parts. The lesions in patients with ADEM (100%) and NMO (91.3%) had poorly defined margins, while lesions of patients with MS (76.0%) had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%), while lesions in patients with NMO (87.0%) and MS (92.0%) were asymmetrical or unilateral.ConclusionsBrain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases.

The triglyceride-glucose (TyG) index is a reliable surrogate of insulin resistance and a marker for ischemic stroke (IS) incident. Whether the TyG index predicts stroke outcome remains uncertain. This study investigated the prognostic value of the TyG index in critically ill stroke patients. Methods: This was a retrospective observational study that included stroke patients, and all data were extracted from the eICU Collaborative Research Database. The TyG index was calculated as the ln [fasting glucose level (mg/dL) × triglyceride level (mg/dL)/2]. Outcomes included the hospital and intensive care unit (ICU) death. Multivariate logistic regression was used to determine independent risk factors. The smoothing curves and forest plots were illustrated. Results: A total of 4,570 eligible subjects were enrolled. The mean level of TyG index was 9.1 ± 0.7. The hospital and ICU mortality rate were 10.3 and 5.0%, respectively. TyG index as a continuous variable was associated hospital mortality in univariate analysis (OR 1.723, 95% CI 1.524-1.948, P < 0.001), adjusted model 1 (OR 1.861, 95% CI 1637-2.116, P < 0.001), and adjusted model 2 (OR 2.543, 95% CI 1.588-4.073, P < 0.001). TyG was also associated ICU mortality in univariate analysis (OR 2.146, 95% CI 1.826-2.523, P < 0.001), adjusted model 1 (OR 2.183, 95% CI 1.847-2.580, P < 0.001), and adjusted model 2 (OR 2.672, 95% CI 1.376-5.188, P < 0.001). The smoothing curves observed a continuous linear association after adjusting all covariates both in hospital and ICU mortality. Subgroup analysis demonstrated TyG index was associated with increased risk of hospital and ICU death in critically ill IS (P < 0.05), but not in hemorrhage stroke (P > 0.05). Conclusion: The TyG index is a potential predictor for hospital and ICU mortality in critically ill stroke patients, especially in IS patients.

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) can coexist with non-organ-specific or organ-specific autoimmune diseases. The aim of this study was to investigate and compare the features between NMOSD without and with autoimmune diseases, and NMOSD with non-organ-specific and organ-specific autoimmune diseases.MethodsOne hundred and fifty five NMOSD patients without autoimmune diseases (n = 115) and with autoimmune diseases (n = 40) were enrolled. NMOSD with autoimmune diseases were divided by organ-specific autoimmune diseases. The clinical, laboratory and magnetic resonance imaging features between two groups were assessed.ResultsMotor deficit was less frequent in NMOSD patients with non-organ-specific autoimmune diseases (p = 0.024). Cerebrospinal fluid white blood cell and protein, serum C-reactive protein and immunoglobulin G were lower in NMOSD patients without autoimmune diseases, while several autoantibodies seropositivity and thyroid indexes were significantly higher in NMOSD patients with autoimmune diseases (p < 0.05). No difference was found in other clinical and laboratory characteristics between different NMOSD subtypes (p > 0.05). NMOSD patients with autoimmune diseases had higher brain abnormalities than NMOSD without autoimmune diseases (p < 0.001).ConclusionsThe characteristics between NMOSD without and with autoimmune diseases were similar. NMOSD with autoimmune diseases have high frequency of brain abnormalities.

Aging and aging‐related CNS diseases are associated with inflammatory status. As an efficient amplifier of immune responses, inflammasome is activated and played detrimental role in aging and aging‐related CNS diseases. Macrophage and microglia display robust inflammasome activation in infectious and sterile inflammation. This review discussed the impact of inflammasome activation in microglia/macrophage on senescence “inflammaging” and aging‐related CNS diseases. The preventive or therapeutic effects of targeting inflammasome on retarding aging process or tackling aging‐related diseases are also discussed.

Brainstem involvement, especially the medulla oblongata (MO), has been reported in neuromyelitis optica spectrum disorders (NMOSDs). The purpose of this study was to investigate retrospectively and compare clinical, laboratory, and imaging features of NMOSDs with and without MO lesions. A total of 170 patients with NMOSDs were enrolled, including 44 patients with MO lesions and 126 patients without MO lesions. Clinical features, laboratory tests, and magnetic resonance imaging findings among these patients were assessed. MO lesions were found in 25.9 % of the NMOSDs patients. The mean duration was 13 months. Patients with MO lesions had a higher Annualized relapse rate and Expanded Disability Status Score Scale. Headache, dizziness, nystagmus, dysarthria, intractable hiccup and nausea, choking cough or dysphagia, movement disorders, and neuropathic pain were more common in MO lesion patients. Patients with MO lesions were more frequently complicated with thyroid diseases. Multiple brain involvement, More importantly, Longitudinally extensive transverse myelitis were more frequently found in patients with MO lesions. MO lesions might be a symbol of more severe neurologic deficits and worse prognosis of NMOSDs.

Natural tissues are composed of ordered architectural organizations of multiple tissue cells. The spatial distribution of cells is crucial for directing cellular behavior and maintaining tissue homeostasis and function. Herein, an artificial bone bioceramic scaffold with star-, Tai Chi-, or interlacing-shaped multicellular patterns is constructed. The "cross-talk" between mesenchymal stem cells (MSCs) and macrophages can be effectively manipulated by altering the spatial distribution of two kinds of cells in the scaffolds, thus achieving controllable modulation of the scaffold-mediated osteo-immune responses. Compared with other multicellular patterns, the Tai Chi pattern with a 2:1 ratio of MSCs to macrophages is more effective in activating anti-inflammatory M2 macrophages, improving MSCs osteogenic differentiation, and accelerating new bone formation in vivo. In brief, the Tai Chi pattern generates a more favorable osteo-immune environment for bone regeneration, exhibiting enhanced immunomodulation and osteogenesis, which may be associated with the activation of BMP-Smad, Oncostatin M (OSM), and Wnt/𝜷-catenin signaling pathways in MSCs mediated by macrophage-derived paracrine signaling mediators. The study suggests that the manipulation of cell distribution to improve tissue formation is a feasible approach that can offer new insights for the design of tissue-engineered bone substitutes with multicellular interactions.