Stroke and Vascular Neurology最新文献

{"title":"Development of machine learning-based models to predict 10-year risk of cardiovascular disease: a prospective cohort study.","authors":"Jia You, Yu Guo, Ju-Jiao Kang, Hui-Fu Wang, Ming Yang, Jian-Feng Feng, Jin-Tai Yu, Wei Cheng","doi":"10.1136/svn-2023-002332","DOIUrl":"10.1136/svn-2023-002332","url":null,"abstract":"<p><strong>Background: </strong>Previous prediction algorithms for cardiovascular diseases (CVD) were established using risk factors retrieved largely based on empirical clinical knowledge. This study sought to identify predictors among a comprehensive variable space, and then employ machine learning (ML) algorithms to develop a novel CVD risk prediction model.</p><p><strong>Methods: </strong>From a longitudinal population-based cohort of UK Biobank, this study included 473 611 CVD-free participants aged between 37 and 73 years old. We implemented an ML-based data-driven pipeline to identify predictors from 645 candidate variables covering a comprehensive range of health-related factors and assessed multiple ML classifiers to establish a risk prediction model on 10-year incident CVD. The model was validated through a leave-one-center-out cross-validation.</p><p><strong>Results: </strong>During a median follow-up of 12.2 years, 31 466 participants developed CVD within 10 years after baseline visits. A novel UK Biobank CVD risk prediction (UKCRP) model was established that comprised 10 predictors including age, sex, medication of cholesterol and blood pressure, cholesterol ratio (total/high-density lipoprotein), systolic blood pressure, previous angina or heart disease, number of medications taken, cystatin C, chest pain and pack-years of smoking. Our model obtained satisfied discriminative performance with an area under the receiver operating characteristic curve (AUC) of 0.762±0.010 that outperformed multiple existing clinical models, and it was well-calibrated with a Brier Score of 0.057±0.006. Further, the UKCRP can obtain comparable performance for myocardial infarction (AUC 0.774±0.011) and ischaemic stroke (AUC 0.730±0.020), but inferior performance for haemorrhagic stroke (AUC 0.644±0.026).</p><p><strong>Conclusion: </strong>ML-based classification models can learn expressive representations from potential high-risked CVD participants who may benefit from earlier clinical decisions.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":" ","pages":"475-485"},"PeriodicalIF":5.9,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10800279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9414282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced liver X receptor signalling reduces brain injury and promotes tissue regeneration following experimental intracerebral haemorrhage: roles of microglia/macrophages.","authors":"Ruiyi Zhang, Yifei Dong, Yang Liu, Dorsa Moezzi, Samira Ghorbani, Reza Mirzaei, Brian M Lozinski, Jeff F Dunn, V Wee Yong, Mengzhou Xue","doi":"10.1136/svn-2023-002331","DOIUrl":"10.1136/svn-2023-002331","url":null,"abstract":"<p><strong>Background: </strong>Inflammation-exacerbated secondary brain injury and limited tissue regeneration are barriers to favourable prognosis after intracerebral haemorrhage (ICH). As a regulator of inflammation and lipid metabolism, Liver X receptor (LXR) has the potential to alter microglia/macrophage (M/M) phenotype, and assist tissue repair by promoting cholesterol efflux and recycling from phagocytes. To support potential clinical translation, the benefits of enhanced LXR signalling are examined in experimental ICH.</p><p><strong>Methods: </strong>Collagenase-induced ICH mice were treated with the LXR agonist GW3965 or vehicle. Behavioural tests were conducted at multiple time points. Lesion and haematoma volume, and other brain parameters were assessed using multimodal MRI with T2-weighted, diffusion tensor imaging and dynamic contrast-enhanced MRI sequences. The fixed brain cryosections were stained and confocal microscopy was applied to detect LXR downstream genes, M/M phenotype, lipid/cholesterol-laden phagocytes, oligodendrocyte lineage cells and neural stem cells. Western blot and real-time qPCR were also used. CX3CR1^CreER: Rosa26^iDTR mice were employed for M/M-depletion experiments.</p><p><strong>Results: </strong>GW3965 treatment reduced lesion volume and white matter injury, and promoted haematoma clearance. Treated mice upregulated LXR downstream genes including ABCA1 and Apolipoprotein E, and had reduced density of M/M that apparently shifted from proinflammatory interleukin-1β⁺ to Arginase1⁺CD206⁺ regulatory phenotype. Fewer cholesterol crystal or myelin debris-laden phagocytes were observed in GW3965 mice. LXR activation increased the number of Olig2⁺PDGFRα⁺ precursors and Olig2⁺CC1⁺ mature oligodendrocytes in perihaematomal regions, and elevated SOX2⁺ or nestin⁺ neural stem cells in lesion and subventricular zone. MRI results supported better lesion recovery by GW3965, and this was corroborated by return to pre-ICH values of functional rotarod activity. The therapeutic effects of GW3965 were abrogated by M/M depletion in CX3CR1^CreER: Rosa26^iDTR mice.</p><p><strong>Conclusions: </strong>LXR agonism using GW3965 reduced brain injury, promoted beneficial properties of M/M and facilitated tissue repair correspondent with enhanced cholesterol recycling.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":" ","pages":"486-502"},"PeriodicalIF":5.9,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10800269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9397922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photochemically induced thalamus infarction impairs cognition in a mouse model.","authors":"Chen Zhang, Shiping Li, Yongjun Wang, Jiong Shi","doi":"10.1136/svn-2022-002235","DOIUrl":"10.1136/svn-2022-002235","url":null,"abstract":"<p><strong>Background: </strong>Small subcortical infarcts account for up to 25% of ischaemic strokes. Thalamus is one of the subcortical structures that commonly manifest with lacunar infarcts on MRI of the brain. Studies have shown that thalamus infarction is associated with cognitive decline. However, due to the lack of proper animal models, little is known about the mechanism. We aimed to establish a focal thalamus infarction model, characterise the infarct lesion and assess functional effects.</p><p><strong>Methods: </strong>Male C57BL/6J mice were anaesthetised, and Rose Bengal dye was injected through the tail vein. The right thalamus was illuminated with green laser light by stereotactic implantation of optic fibre. Characteristics of the infarct and lesion evolution were evaluated by histological analysis and 7T MRI at various times. The cognitive and neurological functions were assessed by behavioural tests. Retrograde tracing was performed to analyse neural connections.</p><p><strong>Results: </strong>An ischaemic lesion with small vessel occlusion was observed in the thalamus. It became a small circumscribed infarct with reactive astrocytes accumulated in the infarct periphery on day 21. The mice with thalamic infarction demonstrated impaired learning and memory without significant neurological deficits. Retrogradely labelled neurons in the retrosplenial granular cortex were reduced.</p><p><strong>Conclusion: </strong>This study established a mouse model of thalamic lacunar infarction that exhibits cognitive impairment. Neural connection dysfunctions may play a potential role in post-stroke cognitive impairment. This model helps to clarify the pathophysiology of post-stroke cognitive impairment and to develop potential therapies.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":" ","pages":"444-452"},"PeriodicalIF":5.9,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10800257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9524231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical evaluation of ZL006-05, a new antistroke drug with fast-onset antidepressant and anxiolytic effects.","authors":"Haiyin Wu, Zhenquan Huang, Xuan Wang, Mingyu Chen, Wei Chen, Yao Hua, Jian Ren, Luyao Shen, Yixuan Song, Ying Zhou, Chunxia Luo, Yuhui Lin, Yilong Wang, Lei Chang, Fei Li, Dongya Zhu","doi":"10.1136/svn-2022-002156","DOIUrl":"10.1136/svn-2022-002156","url":null,"abstract":"<p><strong>Background: </strong>Poststroke depression and anxiety, independent predictor of poor functional outcomes, are common in the acute phase of stroke. Up to now, there is no fast-onset antidepressive and anxiolytic agents suitable for the management of acute stroke. ZL006-05, a dual-target analgesic we developed, dissociates nitric oxide synthase from postsynaptic density-95 while potentiates α2-containing γ-aminobutyric acid type A receptor. This study aims to determine whether ZL006-05 can be used as an antistroke agent with fast-onset antidepressant and anxiolytic effects.</p><p><strong>Methods: </strong>Photothrombotic stroke and transient middle cerebral artery occlusion were induced in rats and mice. Infarct size was measured by TTC(2,3,5-Triphenyltetrazolium chloride) staining or Nissl staining. Neurological defects were assessed by four-point scale neurological score or modified Neurological Severity Scores. Grid-walking, cylinder and modified adhesive removal tasks were conducted to assess sensorimotor functions. Spatial learning was assessed using Morris water maze task. Depression and anxiety were induced by unpredictable chronic mild stress. Depressive behaviours were assessed by tail suspension, forced swim and sucrose preference tests. Anxiety behaviours were assessed by novelty-suppressed feeding and elevated plus maze tests. Pharmacokinetics, toxicokinetics and long-term toxicity studies were performed in rats.</p><p><strong>Results: </strong>Administration of ZL006-05 in the acute phase of stroke attenuated transient and permanent ischaemic injury and ameliorated long-term functional impairments significantly, with a treatment window of 12 hours after ischemia, and reduced plasminogen activato-induced haemorrhagic transformation. ZL006-05 produced fast-onset antidepressant and anxiolytic effects with onset latency of 1 hour in the normal and CMS mice, had antidepressant and anxiolytic effects in stroke mice. ZL006-05 crossed the blood-brain barrier and distributed into the brain rapidly, and had a high safety profile in toxicokinetics and long-term toxicological studies.</p><p><strong>Conclusion: </strong>ZL006-05 is a new neuroprotectant with fast-onset antidepressant and anxiolytic effects and has translational properties in terms of efficacy, safety and targeting of clinical issues.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":" ","pages":"463-474"},"PeriodicalIF":5.9,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10800258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9524232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebral haemodynamics in symptomatic intracranial atherosclerotic disease: a narrative review of the assessment methods and clinical implications.","authors":"Yuying Liu, Shuang Li, Xuan Tian, Thomas W Leung, Liping Liu, David S Liebeskind, Xinyi Leng","doi":"10.1136/svn-2023-002333","DOIUrl":"10.1136/svn-2023-002333","url":null,"abstract":"<p><p>Intracranial atherosclerotic disease (ICAD) is a common cause of ischaemic stroke and transient ischaemic attack (TIA) with a high recurrence rate. It is often referred to as intracranial atherosclerotic stenosis (ICAS), when the plaque has caused significant narrowing of the vessel lumen. The lesion is usually considered 'symptomatic ICAD/ICAS' (sICAD/sICAS) when it has caused an ischaemic stroke or TIA. The severity of luminal stenosis has long been established as a prognostic factor for stroke relapse in sICAS. Yet, accumulating studies have also reported the important roles of plaque vulnerability, cerebral haemodynamics, collateral circulation, cerebral autoregulation and other factors in altering the stroke risks across patients with sICAS. In this review article, we focus on cerebral haemodynamics in sICAS. We reviewed imaging modalities/methods in assessing cerebral haemodynamics, the haemodynamic metrics provided by these methods and application of these methods in research and clinical practice. More importantly, we reviewed the significance of these haemodynamic features in governing the risk of stroke recurrence in sICAS. We also discussed other clinical implications of these haemodynamic features in sICAS, such as the associations with collateral recruitment and evolution of the lesion under medical treatment, and indications for more individualised blood pressure management for secondary stroke prevention. We then put forward some knowledge gaps and future directions on these topics.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":" ","pages":"521-530"},"PeriodicalIF":5.9,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10800270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9390589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Somatic <i>GJA4</i> mutation in intracranial extra-axial cavernous hemangiomas.","authors":"Ran Huo, Yingxi Yang, Hongyuan Xu, Shaozhi Zhao, Dong Song, Jiancong Weng, Ruochen Ma, Yingfan Sun, Jie Wang, Yuming Jiao, Junze Zhang, Qiheng He, Ruolei Wu, Shuo Wang, Ji-Zong Zhao, Junting Zhang, Jiguang Wang, Yong Cao","doi":"10.1136/svn-2022-002227","DOIUrl":"10.1136/svn-2022-002227","url":null,"abstract":"<p><strong>Objective: </strong>Extra-axial cavernous hemangiomas (ECHs) are sporadic and rare intracranial occupational lesions that usually occur within the cavernous sinus. The aetiology of ECHs remains unknown.</p><p><strong>Methods: </strong>Whole-exome sequencing was performed on ECH lesions from 12 patients (discovery cohort) and droplet digital polymerase-chain-reaction (ddPCR) was used to confirm the identified mutation in 46 additional cases (validation cohort). Laser capture microdissection (LCM) was carried out to capture and characterise subgroups of tissue cells. Mechanistic and functional investigations were carried out in human umbilical vein endothelial cells and a newly established mouse model.</p><p><strong>Results: </strong>We detected somatic <i>GJA4</i> mutation (c.121G>T, p.G41C) in 5/12 patients with ECH in the discovery cohort and confirmed the finding in the validation cohort (16/46). LCM followed by ddPCR revealed that the mutation was enriched in lesional endothelium. In vitro experiments in endothelial cells demonstrated that the <i>GJA4</i> mutation activated SGK-1 signalling that in turn upregulated key genes involved in cell hyperproliferation and the loss of arterial specification. Compared with wild-type littermates, mice overexpressing the <i>GJA4</i> mutation developed ECH-like pathological morphological characteristics (dilated venous lumen and elevated vascular density) in the retinal superficial vascular plexus at the postnatal 3 weeks, which were reversed by an SGK1 inhibitor, EMD638683.</p><p><strong>Conclusions: </strong>We identified a somatic <i>GJA4</i> mutation that presents in over one-third of ECH lesions and proposed that ECHs are vascular malformations due to <i>GJA4</i>-induced activation of the SGK1 signalling pathway in brain endothelial cells.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":" ","pages":"453-462"},"PeriodicalIF":5.9,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10800255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9511845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world evaluation of Brainomix e-Stroke software","authors":"D. Mallon, Matthew Fallon, Eirini Blana, Cillian McNamara, Arathi Menon, Chak Lam Ip, Jack Garnham, Tarek Yousry, Peter Cowley, Rob J Simister, David Doig","doi":"10.1136/svn-2023-002859","DOIUrl":"https://doi.org/10.1136/svn-2023-002859","url":null,"abstract":"Brainomix e-Stroke is an artificial intelligence-based decision support tool that aids the interpretation of CT imaging in the context of acute stroke. While e-Stroke has the potential to improve the speed and accuracy of diagnosis, real-world validation is essential. The aim of this study was to prospectively evaluate the performance of Brainomix e-Stroke in an unselected cohort of patients with suspected acute ischaemic stroke.The study cohort included all patients admitted to the University College London Hospital Hyperacute Stroke Unit between October 2021 and April 2022. For e-ASPECTS and e-CTA, the ground truth was determined by a neuroradiologist with access to all clinical and imaging data. For e-CTP, the values of the core infarct and ischaemic penumbra were compared with those derived from syngo.via, an alternate software used at our institution.1163 studies were performed in 551 patients admitted during the study period. Of these, 1130 (97.2%) were successfully processed by e-Stroke in an average of 4 min. For identifying acute middle cerebral artery territory ischaemia, e-ASPECTS had an accuracy of 77.0% and was more specific (83.5%) than sensitive (58.6%). The accuracy for identifying hyperdense thrombus was lower (69.1%), which was mainly due to many false positives (positive predictive value of 22.9%). Identification of acute haemorrhage was highly accurate (97.8%) with a sensitivity of 100% and a specificity of 97.6%; false positives were typically caused by areas of calcification. The accuracy of e-CTA for large vessel occlusions was 91.5%. The core infarct and ischaemic penumbra volumes provided by e-CTP strongly correlated with those provided by syngo.via (ρ=0.804—0.979).Brainomix e-Stroke software provides rapid and reliable analysis of CT imaging in the acute stroke setting although, in line with the manufacturer’s guidance, it should be used as an adjunct to expert interpretation rather than a standalone decision-making tool.","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":"43 35","pages":""},"PeriodicalIF":5.9,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138946665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When treating acute ischaemic stroke of LVO type, time window prevails over tissue window","authors":"X. Huo, A. Jin, Zhongrong Miao, Yongjun Wang, David Wang","doi":"10.1136/svn-2023-003007","DOIUrl":"https://doi.org/10.1136/svn-2023-003007","url":null,"abstract":"","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":"73 3","pages":""},"PeriodicalIF":5.9,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138948103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of early anticoagulation after endovascular treatment in patients with atrial fibrillation.","authors":"Yaning Xu, Chengchun Liu, Wei Li, Ximing Nie, Shuhan Huang, Xiaoshu Li, Ya Wu, Wang-Sheng Jin, Jiaojin Jiang, Jun Dong, Yi Yang, Zhiqiang Sun, Wenjun Han, Yanjiang Wang, Liping Liu, Meng Zhang","doi":"10.1136/svn-2022-002082","DOIUrl":"10.1136/svn-2022-002082","url":null,"abstract":"<p><strong>Background: </strong>The timing for initiating anticoagulant therapy in acute ischaemic stroke (AIS) patients with atrial fibrillation who recanalised after endovascular treatment (EVT) is unclear. The objective of this study was to evaluate the effect of early anticoagulation after successful recanalisation in AIS patients with atrial fibrillation.</p><p><strong>Methods: </strong>Patients with anterior circulation large vessel occlusion and atrial fibrillation who were successfully recanalised by EVT within 24 hours after stroke in the Registration Study for Critical Care of Acute Ischemic Stroke after Recanalization registry were analysed. Early anticoagulation was defined as the initiation of unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) within 72 hours after EVT. Ultra-early anticoagulation was defined if it was initiated within 24 hours. The primary efficacy outcome was the score on the modified Rankin Scale (mRS) at day 90, and the primary safety outcome was symptomatic intracranial haemorrhage within 90 days.</p><p><strong>Results: </strong>Overall, 257 patients were enrolled, of whom 141 (54.9%) initiated anticoagulation within 72 hours after EVT, including 111 within 24 hours. A significant shift towards better mRS scores at day 90 was associated with early anticoagulation (adjusted common OR 2.08 (95% CI 1.27 to 3.41)). Symptomatic intracranial haemorrhage was comparable between patients treated with early and routine anticoagulation (adjusted OR 0.20 (95% CI 0.02 to 2.18)). Comparison of different early anticoagulation regimens showed that ultra-early anticoagulation was more significantly associated with favourable functional outcomes (adjusted common OR 2.03 (95% CI 1.20 to 3.44)) and reduced the incidence of asymptomatic intracranial haemorrhage (OR 0.37 (95% CI 0.14 to 0.94)).</p><p><strong>Conclusions: </strong>In AIS patients with atrial fibrillation, early anticoagulation with UFH or LMWH after successful recanalisation is associated with favourable functional outcomes without increasing the risk of symptomatic intracranial haemorrhages.</p><p><strong>Trial registration number: </strong>ChiCTR1900022154.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":" ","pages":"405-412"},"PeriodicalIF":5.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10647876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9252678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Group 2 innate lymphoid cells resolve neuroinflammation following cerebral ischaemia.","authors":"Pei Zheng, Yuwhen Xiu, Zhili Chen, Meng Yuan, Yan Li, Ningning Wang, Bohao Zhang, Xin Zhao, Minshu Li, Qiang Liu, Fu-Dong Shi, Wei-Na Jin","doi":"10.1136/svn-2022-001919","DOIUrl":"10.1136/svn-2022-001919","url":null,"abstract":"<p><strong>Background: </strong>Acute brain ischaemia elicits pronounced inflammation, which aggravates neural injury. However, the mechanisms governing the resolution of acute neuroinflammation remain poorly understood. In contrast to regulatory T and B cells, group 2 innate lymphoid cells (ILC2s) are immunoregulatory cells that can be swiftly mobilised without antigen presentation; whether and how these ILC2s participate in central nervous system inflammation following brain ischaemia is still unknown.</p><p><strong>Methods: </strong>Leveraging brain tissues from patients who had an ischaemic stroke and a mouse model of focal ischaemia, we characterised the presence and cytokine release of brain-infiltrating ILC2s. The impact of ILC2s on neural injury was evaluated through antibody depletion and ILC2 adoptive transfer experiments. Using Rag2^-/-γc^-/- mice receiving passive transfer of IL-4^-/- ILC2s, we further assessed the contribution of interleukin (IL)-4, produced by ILC2s, in ischaemic brain injury.</p><p><strong>Results: </strong>We demonstrate that ILC2s accumulate in the areas surrounding the infarct in brain tissues of patients with cerebral ischaemia, as well as in mice subjected to focal cerebral ischaemia. Oligodendrocytes were a major source of IL-33, which contributed to ILC2s mobilisation. Adoptive transfer and expansion of ILC2s reduced brain infarction. Importantly, brain-infiltrating ILC2s reduced the magnitude of stroke injury severity through the production of IL-4.</p><p><strong>Conclusions: </strong>Our findings revealed that brain ischaemia mobilises ILC2s to curb neuroinflammation and brain injury, expanding the current understanding of inflammatory networks following stroke.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":" ","pages":"424-434"},"PeriodicalIF":5.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10647866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9788580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}