Translational Stroke Research最新文献

{"title":"Neutrophil Extracellular Traps Induce Brain Edema Around Intracerebral Hematoma via ERK-Mediated Regulation of MMP9 and AQP4.","authors":"Jun Tang, Jianhe Yue, Yihao Tao, Guanjian Zhao, Xiaoyao Yi, Maoxin Zhang, Ning Huang, Yuan Cheng","doi":"10.1007/s12975-024-01318-w","DOIUrl":"https://doi.org/10.1007/s12975-024-01318-w","url":null,"abstract":"<p><p>Perihematomal edema (PHE) significantly aggravates secondary brain injury in patients with intracerebral hemorrhage (ICH), yet its detailed mechanisms remain elusive. Neutrophil extracellular traps (NETs) are known to exacerbate neurological deficits and worsen outcomes after stroke. This study explores the potential role of NETs in the pathogenesis of brain edema following ICH. The rat ICH model was created, immunofluorescence and Western blot were used to examine neutrophil accumulation, NET markers citrullinated histone H3 (CitH3) and myeloperoxidase (MPO), tight junction proteins (ZO-1 and Occludin), Aquaporin-4 (AQP4), matrix metalloproteinase-9 (MMP-9), and ERK phosphorylation (p-ERK) in brain tissues surrounding the hematoma. TUNEL staining and behavioral tests were employed to evaluate neuronal apoptosis and neurological dysfunction, while blood-brain barrier (BBB) permeability and brain edema were also measured by Evans blue and brain water content. Furthermore, the molecular mechanisms related to NETs-induced PHE were investigated using NETs, ERK, MMP-9 and AQP4 regulators, respectively. Ly6G⁺ neutrophils surrounding the hematoma developed NETs within 3 days post-ICH. NETs decreased tight junction proteins, destroyed BBB integrity, promoted brain edema, increased neuronal apoptosis, and exacerbated neurological deficits. Conversely, inhibition of NETs mitigated PHE, reduced neuronal apoptosis, and improved neurological functions. Mechanistically, NET-induced PHE was originated from impairment of BBB tight junction via ERK/MMP9 pathway, coupled with ERK-mediated AQP4 downregulation in perihematomal regions. These findings elucidated the effects of NETs on PHE, which offered promising insights for targeting NETs to relieve brain edema and secondary brain injury post-ICH.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Postprocedural Anticoagulant Use in Patients Undergoing Woven EndoBridge: A Multicenter Propensity Score-Matched Study.","authors":"Basel Musmar, Hamza Adel Salim, Joanna M Roy, Nimer Adeeb, Antony A Fuleihan, Elias Atallah, Saman Sizdahkhani, Sravanthi Koduri, Spyridon Karadimas, Bachar El Baba, Brian M Howard, Jonathan A Grossberg, Kyle W Scott, Jan-Karl Burkhardt, Visish M Srinivasan, Fernanda Erazu, Ricardo A Hanel, Abdelaziz Amllay, Charles Matouk, Andrew MacNeil, Nohra Chalouhi, Santiago Gomez-Paz, Ramesh Grandhi, Vinay Jaikumar, Elad Levy, Adnan Siddiqui, Max Klaiman, Josser Delgado, Haydn Hoffman, Adam Arthur, David M Hasan, Christina Notarianni, Hugo H Cuellar, Bharat Guthikonda, Jacques Morcos, Stavropoula I Tjoumakaris, Michael Reid Gooch, Robert H Rosenwasser, Pascal Jabbour","doi":"10.1007/s12975-024-01320-2","DOIUrl":"https://doi.org/10.1007/s12975-024-01320-2","url":null,"abstract":"<p><p>The Woven EndoBridge (WEB) device has become a prominent treatment for wide-neck bifurcation intracranial aneurysms since its FDA approval in 2018. However, the impact of anticoagulant therapy on its efficacy and patient outcomes remains underexplored. This study aims to evaluate the effects of postoperative anticoagulant use on aneurysm occlusion, retreatment rates, and functional outcomes following WEB device implantation. This retrospective multicenter study included 457 patients treated with the WEB device across 10 academic institutions in the United States between January 2012 and June 2024. Patients were categorized based on postoperative anticoagulant use: 91 patients (19.9%) received anticoagulants, while 366 patients (80.1%) did not. Propensity score matching (PSM) was employed to control for potential confounders, resulting in 316 matched patients (229 non-anticoagulant and 87 anticoagulant). After PSM, the anticoagulant group had lower rates of excellent functional outcomes (mRS 0-1: 73% vs. 85%, p = 0.026) and higher mortality rates (6.7% vs. 3.7%, p = 0.33), though the latter difference was not statistically significant. No significant differences in the last follow-up adequate occlusion were observed between the two groups (p = 0.7). However, patients in the anticoagulant group had lower major device compaction (> 50%) (4.9% vs. 12%, p = 0.12) and retreatment rates (4.6% vs. 12%, p = 0.045). Postoperative anticoagulant use is associated with poor functional outcomes and higher tendency for higher mortality rate. No significant differences in the last follow-up adequate occlusion rate were observed between the anticoagulant group and non-anticoagulant group. However, patients in the anticoagulant group had lower major compaction and retreatment rates. These findings suggest that the WEB mechanism of occlusion is more complex than what have been hypothesized and highlight the need for individualized management strategies to optimize outcomes in patients requiring anticoagulation post-WEB. Further studies are needed.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global and Regional Burden of Ischemic Stroke Disease from 1990 to 2021: An Age-Period-Cohort Analysis.","authors":"Weimin Zhu, Xiaxia He, Daochao Huang, Yiqing Jiang, Weijun Hong, Shaofa Ke, En Wang, Feng Wang, Xianwei Wang, Renfei Shan, Suzhi Liu, Yinghe Xu, Yongpo Jiang","doi":"10.1007/s12975-024-01319-9","DOIUrl":"10.1007/s12975-024-01319-9","url":null,"abstract":"<p><p>Ischemic stroke is a significant global public health issue that impacts health burdens across various regions. This study analyzed data from the Global Burden of Disease Study 2021 to assess the incidence, mortality, and disability-adjusted life years (DALYs) associated with ischemic stroke worldwide and across different Socio-demographic Index (SDI) regions. Using joinpoint regression and age-period-cohort (APC) models, we examined trends in disease burden and made projections for 2022 to 2035. As of 2021, approximately 7,804,449 (95% UI, 6,719,760-8,943,692) individuals were affected by ischemic stroke, resulting in 3,591,499 (95% UI, 3,213,281-3,888,327) deaths and 70,357,912 (95% UI, 64,329,576-76,007,063) DALYs. These numbers represent increases of 88.0%, 55.0%, and 52.4% since 1990. Despite these increases, age-standardized incidence, mortality, and DALYs rates are declining, with annual percentage change rates (AAPC) of - 0.578%, - 0.927%, and - 14.372%, consistent across all SDI regions. The global rates of IS are influenced by age, period, and cohort, showing increased rates with age but declining over time, particularly in high SDI regions. Major risk factors include hypertension, environmental pollution, and low-density lipoprotein cholesterol (LDL-C). Projections indicate that by 2035, incidence, mortality, and DALYs will rise among those aged 45 and above, while decreasing for those under 35. This highlights the urgent need for preventive and therapeutic strategies targeting ischemic stroke, particularly for individuals over 45, while addressing the impact of major risk factors in high-burden regions.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Composition of Acute Ischemic Stroke Thrombi Retrieved via Endovascular Thrombectomy Is Associated with Stroke Etiology.","authors":"Run-Hao Jiang, Xing-Long Liu, Xiao-Quan Xu, Hai-Bin Shi, Sheng Liu","doi":"10.1007/s12975-024-01317-x","DOIUrl":"https://doi.org/10.1007/s12975-024-01317-x","url":null,"abstract":"<p><p>The objective of this study is to investigate the protein components of acute ischemic stroke (AIS) thrombi using four-dimensional independent data acquisition (4D-DIA) proteomics and reveal the correlations between thrombotic protein components and AIS etiology. From April to September 2023, we enrolled a total of 30 patients who underwent endovascular thrombectomy at our institute and were diagnosed in accordance with large artery atherosclerosis (LAA; n = 15) or cardioembolism (CE; n = 15). Thromboembolic material was collected for 4D-DIA proteomic detection. We then analyzed it for differentially expressed proteins (DEPs; fold change [FC] ≥ 1.5 or ≤ 0.67), performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, and mapped protein-protein interactions (PPIs). In the 30 retrieved clots, 5115 proteins were expressed. Of these, we screened 246 DEPs between the LAA and CE groups, such as histone H4, collagen α1, and differentially expressed in neoplastic versus normal cells domain-containing protein 6A. GO analysis revealed that the DEPs' most important biological process was cellular process, the most important Cell Component was cell part, the molecular function was binding, and the most significantly enriched pathway was thiamine metabolism. PPI results revealed complicated interactions among these DEPs, of which superoxide dismutase, catalase, and γ-enolase might play important roles. This study outlines a promising molecular approach to differentiating the etiology of AIS between CE and LAA through the proteomics of retrieved thrombi, which might also inform future research into thrombotic biology.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enlarged Perivascular Spaces (EPVS) Associated with Functional and Cognitive Outcome After Aneurysm Subarachnoid Hemorrhage (aSAH).","authors":"Haichao Wang, Qiuyue Yu, Wenyi Zhang, Shengqi Yao, Yun Zhang, Qiong Dong, Yichen Zhao, Jinxing Lin, Xueyuan Liu, Li Gong","doi":"10.1007/s12975-024-01315-z","DOIUrl":"https://doi.org/10.1007/s12975-024-01315-z","url":null,"abstract":"<p><p>Aneurysmal rupture is the main cause of subarachnoid hemorrhage (SAH), leading to neurological and cognitive deficits. The clinical significance of enlarged perivascular spaces (EPVS) on aSAH (aneurysm subarachnoid hemorrhage) outcomes was unclear. Our aim was to explore the association between EPVS and the clinical outcomes of aSAH. Magnetic resonance imaging (MRI) scans of 195 aSAH survivors were analyzed. Poor outcome was defined as modified Rankin Scale (mRS) ≥ 3. Cognitive outcomes were measured with the Montreal Cognitive Assessment (MoCA). We compared the clinical characteristics of aSAH with EPVS < 10 and EPVS ≥ 10 in basal ganglia (BG) and centrum semiovale (CSO) and investigated the association of EPVS severity and topography with delayed cerebral ischemia (DCI), subacute hydrocephalus, and 3-month unfavorable functional outcome and cognitive status using binary logistic regression model, respectively. At 3 months, 159 patients completed the MoCA assessments, and 63 (39.6%) were diagnosed with cognitive impairment (MoCA < 22). BG-EPVS ≥ 10 was associated with unfavorable functional outcomes at 3 months (odds ratio [OR] 2.426, 95% confidence interval [CI] 1.128-5.216, p < 0.05), subacute hydrocephalus (OR 3.789, 95% CI 1.049-13.093, p < 0.05), and DCI (OR 2.579, 95% CI 1.086-6.123, p < 0.05), but not with cognitive impairment after adjusting for established predictors. CSO-EPVS was linked to unfavorable functional outcomes at 3 months (OR 3.411, 95% CI 1.422-8.195, p < 0.05) and worse cognitive function (OR 2.520, 95% CI 1.136-5.589, p < 0.05). Our cohort study reveals that both BG-EPVS and CSO-EPVS are independently associated with unfavorable functional outcomes after aSAH. However, only CSO-EPVS, not BG-EPVS, is related to cognitive impairment at 3 months.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Monro-Kellie Doctrine: Contralateral Hemisphere Shrinkage in Intracerebral Hemorrhage Patients.","authors":"Elmira Khiabani, Anna C J Kalisvaart, Cassandra M Wilkinson, Peter L Hurd, Brian H Buck, Frederick Colbourne","doi":"10.1007/s12975-024-01316-y","DOIUrl":"https://doi.org/10.1007/s12975-024-01316-y","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH) along with aggravating factors, such as edema, can raise intracranial pressure (ICP) to pathological levels. Diversion of some cerebrospinal fluid (CSF) and venous blood out of the cranium can limit ICP rises while maintaining cerebral perfusion pressure. Brain tissue itself is widely considered immutable in volume but prone to distortion (e.g., midline shift). However, distal brain regions shrink acutely following ICH in rodents. Tissue contraction arises from cell shrinkage and increased packing density. This \"tissue compliance\" is hypothesized to be an additional mechanism to limit ICP rises. Here, we examined whether and by how much parenchyma volume reduction occurs in ICH patients. We conducted a retrospective analysis on computed tomography (CT) scans of 96 ICH patients (average age 63.8 years old, 55% male) with an average hematoma volume of 32.4 and 35.3 mL at the first and second scan (separated by ~ 23 h), respectively. Hematoma growth (any absolute increase) occurred in 44% of patients, with a minimal but significant growth of the hematoma of 2.9 mL on average across all patients (p = 0.028). As hypothesized, the contralateral hemisphere volume was significantly reduced by 12.7 mL (p < 0.0001) between scans. This was unrelated to midline shift (R² = 0.012, p = 0.21), which averaged 2.3 mm. These findings suggest that distal parenchymal shrinkage may be a major compliance mechanism after ICH; the implications for ICP and brain function merit further study.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TdCCA with Dual-Modal Signal Fusion: Degenerated Occipital and Frontal Connectivity of Adult Moyamoya Disease for Early Identification.","authors":"Yuchen Ran, Yingwei Fan, Shuang Wu, Chao Chen, Yangxi Li, Tianxin Gao, Houdi Zhang, Cong Han, Xiaoying Tang","doi":"10.1007/s12975-024-01313-1","DOIUrl":"https://doi.org/10.1007/s12975-024-01313-1","url":null,"abstract":"<p><p>Cognitive impairment in patients with moyamoya disease (MMD) manifests earlier than clinical symptoms. Early identification of brain connectivity changes is essential for uncovering the pathogenesis of cognitive impairment in MMD. We proposed a temporally driven canonical correlation analysis (TdCCA) method to achieve dual-modal synchronous information fusion from electroencephalogram (EEG) and functional near-infrared spectroscopy (fNIRS) for exploring the differences in brain connectivity between MMD and normal control groups. The dual-modal fusion features were extracted based on the imaginary part of coherence of the EEG signal (EEG iCOH) and the Pearson correlation coefficients of the fNIRS signal (fNIRS COR) in the resting and working memory state. The machine learning model showed that the accuracy of TdCCA method reached 97%, far higher than single-modal features and feature-level fusion CCA method. Brain connectivity analysis revealed a significant reduction in the strength of the connections between the right occipital lobe and frontal lobes (EEG iOCH: p = 0.022, fNIRS COR p = 0.011) in MMD. These differences reflected the impaired transient memory and executive function in MMD patients. This study contributes to the understanding of the neurophysiological nature of cognitive impairment in MMD and provides a potential adjuvant early identification method for individuals with chronic cerebral ischemia.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Analysis of Stent-Assisted Versus Non-Stent-Assisted Coiling in the Management of Ruptured Intracranial Aneurysms: A Systematic Review and Meta-Analysis.","authors":"Yu-Hu Ma, Yong-Lin He, Xiao-Yue Zhang, Rui Shang, Hai-Tao Hu, Ting Wang, Sen Lin, Ya-Wen Pan, Chang-Wei Zhang","doi":"10.1007/s12975-024-01314-0","DOIUrl":"https://doi.org/10.1007/s12975-024-01314-0","url":null,"abstract":"<p><strong>Objective: </strong>To systematically evaluate the safety and efficacy of SAC compared to non-SAC in the treatment of RIA, integrating evidence from high-quality studies to guide clinical practice.</p><p><strong>Methods: </strong>A meta-analysis was conducted to compare SAC with coiling alone and BAC in the treatment of RIA. Primary outcomes were immediate and follow-up aneurysm occlusion rates, along with perioperative hemorrhagic and ischemic complication rates.</p><p><strong>Results: </strong>A total of thirteen retrospective cohort studies were included, comprising 3,086 patients, with 1,078 in the SAC group and 2,008 in the non-SAC group. The immediate complete occlusion rates were similar between the SAC and non-SAC groups (59.1% vs. 61.4%; RR = 1.00; 95% CI [0.94, 1.07]; p = 0.92). However, the SAC group demonstrated a significantly higher long-term complete occlusion rate (61.3% vs. 40.6%; RR = 1.44; 95% CI [1.22, 1.69]; p < 0.001). The incidence of ischemic complications was greater in the SAC group (12.2% vs. 10.0%; RR = 1.68; 95% CI [1.37, 2.07]; p < 0.001), as was the incidence of hemorrhagic complications (7.3% vs. 5.1%; RR = 1.55; 95% CI [1.15, 2.08]; p = 0.004). Perioperative mortality was also elevated in the SAC group (6.7% vs. 6.8%; RR = 1.37; 95% CI [1.00, 1.88]; p = 0.048), with a non-significant trend towards higher long-term mortality (9.8% vs. 9.2%; RR = 1.35; 95% CI [0.98, 1.87]; p = 0.068). Functional outcomes at discharge (76.0% vs. 71.0%; RR = 0.97; 95% CI [0.92, 1.02]; p = 0.237), six months (57.8% vs. 60.8%; RR = 0.93; 95% CI [0.81, 1.07]; p = 0.296), and at the last follow-up (RR = 1.01; 95% CI [0.97, 1.06]; p = 0.592) were comparable between the two groups.</p><p><strong>Conclusions: </strong>SAC significantly improves long-term occlusion rates for RIA compared to non-SAC, despite a higher incidence of complications. Careful patient selection and optimization of antiplatelet therapy may enhance the safety and efficacy of SAC for RIA treatment.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors Influencing Collateral Circulation Formation After Indirect Revascularization for Moyamoya Disease: a Narrative Review.","authors":"Gan Gao, Si-Meng Liu, Fang-Bin Hao, Qian-Nan Wang, Xiao-Peng Wang, Min-Jie Wang, Xiang-Yang Bao, Cong Han, Lian Duan","doi":"10.1007/s12975-023-01185-x","DOIUrl":"10.1007/s12975-023-01185-x","url":null,"abstract":"<p><p>Indirect revascularization is one of the main techniques for the treatment of Moyamoya disease. The formation of good collateral circulation is a key measure to improve cerebral blood perfusion and reduce the risk of secondary stroke, and is the main method for evaluating the effect of indirect revascularization. Therefore, how to predict and promote the formation of collateral circulation before and after surgery is important for improving the success rate of indirect revascularization in Moyamoya disease. Previous studies have shown that vascular endothelial growth factor, endothelial progenitor cells, Caveolin-1, and other factors observed in patients with Moyamoya disease may play a key role in the generation of collateral vessels after indirect revascularization through endothelial hyperplasia and smooth muscle migration. In addition, mutations in the genetic factor RNF213 have also been associated with this process. This study summarizes the factors and mechanisms influencing collateral circulation formation after indirect revascularization in Moyamoya disease.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1005-1014"},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10012205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Non-excitatory Amino Acids and Transporters Mediating the Irreversible Synaptic Silencing After Hypoxia.","authors":"Iris Álvarez-Merz, María-Dolores Muñoz, Jesús M Hernández-Guijo, José M Solís","doi":"10.1007/s12975-023-01192-y","DOIUrl":"10.1007/s12975-023-01192-y","url":null,"abstract":"<p><p>The contribution of excitatory amino acids (AA) to ischemic brain injury has been widely described. In addition, we reported that a mixture of non-excitatory AA at plasmatic concentrations turns irreversible the depression of synaptic transmission caused by hypoxia. Here, we describe that the presence of seven non-excitatory AA (L-alanine, L-glutamine, glycine, L-histidine, L-serine, taurine, and L-threonine) during hypoxia provokes an irreversible neuronal membrane depolarization, after an initial phase of hyperpolarization. The collapse of the membrane potential correlates with a great increase in fiber volley amplitude. Nevertheless, we show that the presence of all seven AA is not necessary to cause the irreversible loss of fEPSP after hypoxia and that the minimal combination of AA able to provoke a solid, replicable effect is the mixture of L-alanine, glycine, L-glutamine, and L-serine. Additionally, L-glutamine seems necessary but insufficient to induce these harmful effects. We also prove that the deleterious effects of the AA mixtures on field potentials during hypoxia depend on both the identity and concentration of the individual AA in the mixture. Furthermore, we find that the accumulation of AA in the whole slice does not determine the outcome caused by the AA mixtures on the synaptic transmission during hypoxia. Finally, results obtained using pharmacological inhibitors and specific substrates of AA transporters suggest that system N and the alanine-serine-cysteine transporter 2 (ASCT2) participate in the non-excitatory AA-mediated deleterious effects during hypoxia. Thus, these AA transporters might represent therapeutical targets for the treatment of brain ischemia.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1070-1087"},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41148934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}