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The neural cell adhesion molecule (NCAM) promotes neural development and regeneration. Whether NCAM mimetic peptides could synergize with bone marrow mesenchymal stem cells (BMSCs) in stroke treatment deserves investigation. We found that the NCAM mimetic peptide P2 promoted BMSC proliferation, migration, and neurotrophic factor expression, protected neurons from oxygen-glucose deprivation through ERK and PI3K/AKT activation and anti-apoptotic mechanisms in vitro. Following middle cerebral artery occlusion (MCAO) in rats, P2 alone or in combination with BMSCs inhibited neuronal apoptosis and induced the phosphorylation of ERK and AKT. P2 combined with BMSCs enhanced neurotrophic factor expression and BMSC proliferation in the ischemic boundary zone. Moreover, combined P2 and BMSC therapy induced translocation of nuclear factor erythroid 2-related factor, upregulated heme oxygenase-1 expression, reduced infarct volume, and increased functional recovery as compared to monotreatments. Treatment with LY294002 (PI3K inhibitor) and PD98059 (ERK inhibitor) decreased the neuroprotective effects of combined P2 and BMSC therapy in MCAO rats. Collectively, P2 is neuroprotective while P2 and BMSCs work synergistically to improve functional outcomes after ischemic stroke, which may be attributed to mechanisms involving enhanced BMSC proliferation and neurotrophic factor release, anti-apoptosis, and PI3K/AKT and ERK pathways activation. [ABSTRACT FROM AUTHOR]

Futile recanalization (FR) after endovascular treatment (EVT) remains a significant challenge for acute ischemic stroke (AIS) with large vessel occlusion (LVO). The pathogenesis of FR has not been well elucidated. We prospectively enrolled anterior circulation LVO-AIS patients who achieved successful recanalization after EVT. The jugular venous blood ipsilateral to stroke was collected before and immediately after recanalization. Plasma proteomic analysis based on liquid chromatography-mass spectrometry was performed using data-independent acquisition method. Differentially expressed proteins (DEPs) among patients with or without FR in the whole or propensity score matching (PSM) cohorts were screened according to the absolute value of fold change ≥1.5 and P value <0.05. We identified 104 and 34 DEPs between patients with or without FR in the whole cohort and PSM cohort, respectively. Bioinformatic analysis indicated that the identified proteins were primarily related to specific biological processes including immune response, complement activation, oxidative stress, lipid metabolism, protein ubiquitylation as well as autophagy, suggesting that these may be mechanisms in FR pathogenesis. Collectively, we discovered proteins that may be potential research targets for FR. The combination of proteomic and bioinformatic analysis could provide a better understanding of the pathogenesis of FR in a comprehensive manner. [ABSTRACT FROM AUTHOR]

Bone marrow mesenchymal stem cells (BMSCs) have been shown to promote stroke recovery, however, the underlying mechanisms are not well understood. In this study naïve rats were intravenously injected with syngeneic BMSCs to screen for potential differences in brain metabolite spectrum versus vehicle-treated controls by capillary electrophoresis-mass spectrometry. A total of 65 metabolites were significantly changed after BMSC treatment. Among them, 5-oxoproline, an intermediate in the biosynthesis of the endogenous glutathione (GSH), was increased. To confirm the obtained results and investigate the metabolic pathways, BMSCs were injected into rats 24 h after middle cerebral artery occlusion (MCAO). Rats receiving vehicle solution and sham-operated animals served as controls. High performance liquid chromatography, reverse transcription-quantitative polymerase chain reaction, and Western blotting revealed that intravenous BMSC application increased the levels of 5-oxoproline and GSH in MCAO rats, as well as the expression of key enzymes involved in GSH synthesis including, gamma-glutamylcyclotransferase and gamma-glutamylcysteine ligase. Subsequent clinical investigation confirmed that acute ischemic stroke patients had higher plasma 5-oxoproline and GSH levels than age- and sex-matched non-stroke controls. The optimal cutoff value for 5-oxoproline diagnosing acute ischemic stroke (≤ 7d) was 3.127 µg/mL (sensitivity, 63.4 %; specificity, 81.2 %) determined by receiver characteristic operator curve. The area under the curve was 0.782 (95 % confidence interval: 0.718–0.845). Our findings indicate that BMSCs play a protective role in ischemic stroke through upregulation of GSH and 5-oxoproline is a potential biomarker for acute ischemic stroke. Ischemic stroke causes oxidative stress and induction of endogenous, glutathione-dependent anti-oxidative mechanisms. 5-oxoproline, an important metabolite in glutathione biosynthesis, could serve as a biomarker of acute ischemic stroke. Moreover, intravenous bone marrow mesenchymal stem cell (BMSC) treatment after experimental stroke upregulates the expression of key enzymes involved in glutathione synthesis, which results in better antioxidative defense and improved stroke outcome. [ABSTRACT FROM AUTHOR]

Background: Timely recognition of futile recanalization might enable a prompter response and thus improve outcomes in patients receiving successful thrombectomy. This study aims to evaluate whether postoperative fibrinogen‐to‐albumin ratio (FAR) could act as an indicator of futile recanalization. Methods: This is a single‐center, retrospective analysis of patients with acute anterior circulation large‐vessel occlusion and successful thrombectomy between May 2019 and June 2022. FAR was defined as postoperative blood levels of fibrinogen divided by those of albumin, and dichotomized into high and low levels based on the Youden index. Futile recanalization was defined as patients achieving a successful recanalization with a modified Rankin Scale score of 3–6 at 90 days. Multivariable logistic regression was used to assess the association of FAR with futile recanalization. Results: A total of 255 patients were enrolled, amongst which 87 patients (34.1%) had high postoperative FAR. Futile recanalization was more prevalent among patients with high FAR compared to those with low FAR (74.7% vs. 53.0%, p =.001). After adjusting for potential confounders, high postoperative FAR was found to independently correspond with the occurrence of futile recanalization (adjusted OR 2.40, 95%CI 1.18–4.87, p =.015). This association was consistently observed regardless of prior antithrombotic therapy, treatment of intravenous thrombolysis, occlusion site, time from symptom onset to groin puncture, and reperfusion status. Conclusion: Our findings support high postoperative FAR serving as an indicator of futile recanalization in patients with anterior circulation large‐vessel occlusion and successful thrombectomy. [ABSTRACT FROM AUTHOR]

Highlights: [•] We report decaploids of A. arguta in nature at the first time. [•] The results evidenced co-existence of 4 cytotypes from 4× to 10× in a natural population of A. arguta in Daba Mountain of China. [•] Fruit characteristics of purple A. arguta have been documented on level of natural population. [ABSTRACT FROM AUTHOR]

Unraveling the pathology of stroke is a prerequisite for designing therapeutic strategies. It was reported that myelin injury exceeded axonal loss in the peri-infarct region of rodent white matter stroke. An in-depth investigation of the post-stroke white matter damage in higher-order species might innovate stroke intervention. In this study, adult male cynomolgus monkeys received surgical middle cerebral artery occlusion (MCAO), and serial magnetic resonance scans to non-invasively assess brain damage. Spontaneous movements were recorded to evaluate post-stroke behavior. The axon and myelin loss, as well as immune cell infiltration were examined using immunohistochemistry. Magnetic resonance imaging revealed cerebral infarcts and white matter injury after MCAO in monkeys, which were confirmed by neurological deficits. Immunostaining of white matter fibers showed substantial demyelination whilst retention of axons in the infarcts 8 days post MCAO, while a progressive loss of myelin and axons was observed after one month. Gliosis, microglia activation, and leukocyte infiltration were identified in the lesions. These results demonstrate that demyelination predates axonal injury in non-human primate ischemic stroke, which provides a time window for stroke intervention focusing on prevention of progressive axonal loss through myelin regeneration. • White matter demyelination predates axon injury in early phase of ischemic stroke. • Multimodality MRI offers comprehensive assessment of experimental stroke lesions. • Non-human primate model ensures high translational significance of stroke study. • Myelin is an important therapeutic target in subacute phase of stroke. [ABSTRACT FROM AUTHOR]

Background: Early and accurate diagnosis of ischaemic stroke (IS) requires the use of an optimized biomarker. Exosomal microRNAs have the potential to serve as biomarkers owing to their stability and specificity. We investigated the expression levels of plasma-derived exosomal microRNA-21-5p and microRNA-30a-5p in the different phases of IS. Methods: One hundred forty-three patients with IS and 24 non-stroke controls were enrolled. The patients were divided into the following 5 groups: 1 group for the hyperacute phase IS (HIS, within 6 h); two for the acute phase IS (AIS, including days 1–3 and days 4–7); one for the subacute phase IS (SIS, days 8–14); and one for the recovery phase IS (RIS, days >14). Plasma exosomes were isolated using a QIAGEN exoRNeasy kit and examined by transmission electron ­microscopy, nanoparticle tracking, and flow cytometry. The expression levels of miRNA-21-5p and miRNA-30a-5p were detected by quantitative real-time polymerase chain reaction. Results: The plasma exosomal miR-21-5p levels in SIS and RIS were significantly higher than that in controls (p < 0.05 and p < 0.01 respectively). The levels of miR-30a-5p in HIS were significantly higher (p < 0.05) and in AIS (days 1–3) were lower than that in controls (p < 0.05). In AIS (days 1–3), both miRNAs were decreased compared with the HIS group (p = 0.053 and 0.001, respectively). The area under the curve (AUC) of the miR-21-5p was 0.714 for SIS (95% CI 0.570–0.859, p = 0.007), 0.734 for RIS (95% CI 0.596–0.871, p = 0.003); the AUC of the miR-30a-5p was 0.826 for HIS (95% CI 0.665–0.988, p = 0.001), 0.438 for AIS (days 1–3; 95% CI 0.240–0.635, p = 0.516). Conclusions: The plasma-derived exosomal miR-21-5p and miRNA-30a-5p in combination are promising biomarkers for diagnosing IS and distinguishing among HIS, SIS, and RIS, especially miRNA-30a-5p for the diagnosis of the HIS phase. Our results provide a new reference for clinicians to apply in early-stage diagnosis and identifies the possible value of biomarkers for IS thrombolysis therapy. [ABSTRACT FROM AUTHOR]