Novel subsets of peripheral immune cells associated with promoting stroke recovery in mice DOI Creative Commons
Yichen Gu, Xiaotao Zhang, Huaming Li

и другие.

CNS Neuroscience & Therapeutics, Год журнала: 2023, Номер 30(4)

Опубликована: Окт. 31, 2023

Abstract Aims Peripheral immune cells infiltrating into the brain trigger neuroinflammation after an ischemic stroke. Partial reprogram their function for neural repair. Which promote recovery needs further identification. Methods We performed single‐cell transcriptomic profiling of CD45 high isolated from hemisphere at subacute (5 days) and chronic (14 stages Results A subset phagocytic macrophages was associated with neuron projection regeneration tissue remodeling. also identified a unique type T highly expressed macrophage markers, including C1q , Apoe Hexb Fcer1g which showed abilities in remodeling, myelination regulation, wound healing, anti‐neuroinflammation. Moreover, natural killer decreased cytotoxicity increased energy metabolic stage Two subgroups neutrophils upregulated CCL signals to recruit peripheral released CXCL2 keep self‐recruiting stage. Conclusions subsets that may provide potential therapeutic targets promoting poststroke recovery.

Язык: Английский

Microglia-mediated neuroinflammation and neuroplasticity after stroke DOI Creative Commons
Yuan Wang, Rehana K. Leak, Guodong Cao

и другие.

Frontiers in Cellular Neuroscience, Год журнала: 2022, Номер 16

Опубликована: Авг. 16, 2022

Stroke remains a major cause of long-term disability and mortality worldwide. The immune system plays an important role in determining the condition brain following stroke. As resident innate cells central nervous system, microglia are primary responders defense network covering entire parenchyma, exert various functions depending on dynamic communications with neurons, astrocytes, other neighboring under both physiological or pathological conditions. Microglia activation polarization is crucial for damage repair ischemic stroke, considered double-edged sword neurological recovery. can exist pro-inflammatory states promote secondary damage, but they also secrete anti-inflammatory cytokines neurotrophic factors facilitate recovery In this review, we focus mechanisms microglia-mediated neuroinflammation neuroplasticity after ischemia relevant potential microglia-based interventions stroke therapy.

Язык: Английский

Процитировано

79

Analysis of brain and blood single-cell transcriptomics in acute and subacute phases after experimental stroke DOI
Lidia García‐Bonilla, Ziasmin Shahanoor, Rose Sciortino

и другие.

Nature Immunology, Год журнала: 2024, Номер 25(2), С. 357 - 370

Опубликована: Янв. 4, 2024

Язык: Английский

Процитировано

65

Neuroimmune mechanisms and therapies mediating post-ischaemic brain injury and repair DOI
Takashi Shichita, Hiroaki Ooboshi, Akihiko Yoshimura

и другие.

Nature reviews. Neuroscience, Год журнала: 2023, Номер 24(5), С. 299 - 312

Опубликована: Март 27, 2023

Язык: Английский

Процитировано

62

Integrating spatial and single-cell transcriptomics to characterize the molecular and cellular architecture of the ischemic mouse brain DOI Open Access
Bing Han, Shunheng Zhou,

Yuan Zhang

и другие.

Science Translational Medicine, Год журнала: 2024, Номер 16(733)

Опубликована: Фев. 7, 2024

Neuroinflammation is acknowledged as a pivotal pathological event after cerebral ischemia. However, there limited knowledge of the molecular and spatial characteristics nonneuronal cells, well interactions between cell types in ischemic brain. Here, we used transcriptomics to study hemisphere mice stroke sequenced transcriptomes 19,777 spots, allowing us both visualize transcriptional landscape within tissue identify gene expression profiles linked specific histologic entities. Cell identified by single-cell RNA sequencing confirmed enriched annotation ischemia-associated peri-infarct area hemisphere. Analysis ligand-receptor communication revealed galectin-9 cell-surface glycoprotein CD44 (LGALS9-CD44) critical signaling pathway injury microglia macrophages main source galectins stroke. Extracellular vesicle–mediated Lgals9 delivery improved long-term functional recovery photothrombotic mice. Knockdown Cd44 partially reversed these therapeutic effects, inhibiting oligodendrocyte differentiation remyelination. In summary, our provides detailed cellular characterization peri-infact murine model potential treatment target that warrants further investigation.

Язык: Английский

Процитировано

35

Role of microglia in stroke DOI Creative Commons
Anna M. Planas

Glia, Год журнала: 2024, Номер 72(6), С. 1016 - 1053

Опубликована: Янв. 4, 2024

Abstract Microglia play key roles in the post‐ischemic inflammatory response and damaged tissue removal reacting rapidly to disturbances caused by ischemia working restore lost homeostasis. However, modified environment, encompassing ionic imbalances, disruption of crucial neuron–microglia interactions, spreading depolarization, generation danger signals from necrotic neurons, induce morphological phenotypic shifts microglia. This leads them adopt a proinflammatory profile heighten their phagocytic activity. From day three post‐ischemia, macrophages infiltrate core while microglia amass at periphery. Further, inflammation prompts metabolic shift favoring glycolysis, pentose‐phosphate shunt, lipid synthesis. These shifts, combined with intake, drive droplet biogenesis, fuel anabolism, enable proliferation. Proliferating release trophic factors contributing protection repair. some accumulate lipids persistently transform into dysfunctional potentially harmful foam cells. Studies also showed that either display impaired apoptotic cell clearance, or eliminate synapses, viable endothelial Yet, it will be essential elucidate viability engulfed cells, features local extent damage, temporal sequence. Ischemia provides rich variety region‐ injury‐dependent stimuli for microglia, evolving time generating distinct phenotypes including those exhibiting traits others showing pro‐repair features. Accurate profiling phenotypes, alongside more precise understanding associated conditions, is necessary step serve as potential foundation focused interventions human stroke.

Язык: Английский

Процитировано

31

Microglia autophagy in ischemic stroke: A double-edged sword DOI Creative Commons
Peng Li,

Guangqiang Hu,

Qianfang Yao

и другие.

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Ноя. 16, 2022

Ischemic stroke (IS) is one of the major types cerebrovascular diseases causing neurological morbidity and mortality worldwide. In pathophysiological process IS, microglia play a beneficial role in tissue repair. However, it could also cause cellular damage, consequently leading to cell death. Inflammation characterized by activation microglia, increasing evidence showed that autophagy interacts with inflammation through regulating correlative mediators signaling pathways. this paper, we summarized harmful effects IS. addition, discussed interplay between ischemic inflammation, as along its application treatment We believe help provide theoretical references for further study into IS treatments future.

Язык: Английский

Процитировано

59

Spatiotemporal Characterization of Human Early Intervertebral Disc Formation at Single‐Cell Resolution DOI Creative Commons
Taifeng Zhou, Yu Chen, Zhiheng Liao

и другие.

Advanced Science, Год журнала: 2023, Номер 10(14)

Опубликована: Март 25, 2023

Abstract The intervertebral disc (IVD) acts as a fibrocartilaginous joint to anchor adjacent vertebrae. Although several studies have demonstrated the cellular heterogeneity of adult mature IVDs, single‐cell transcriptomic atlas mapping early IVD formation is still lacking. Here, authors generate spatiotemporal and single cell‐based human at embryonic stage comparative mouse transcript landscape. They identify two novel notochord (NC)/nucleus pulposus (NP) clusters, SRY‐box transcription factor 10 (SOX10) + cathepsin K (CTSK) , that are distributed in late stages they validated by lineage tracing experiments mice. Matrisome NC/NP T‐box T (TBXT) CTSK responsible for extracellular matrix homeostasis. suggests subcluster vertebral chondrocyte might give rise an inner annulus fibrosus chondrogenic origin, while fibroblastic outer preferentially expresseds transgelin fibromodulin . Through analyzing intercellular crosstalk, further find notochordal secreted phosphoprotein 1 (SPP1) cue microenvironment, it associated with development degeneration. In conclusion, will be leveraged develop preventative regenerative strategies

Язык: Английский

Процитировано

30

Single-nucleus RNA sequencing reveals glial cell type-specific responses to ischemic stroke in male rodents DOI Creative Commons
Daniel Bormann, Michael Knoflach,

Emilia Poreba

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июль 24, 2024

Neuroglia critically shape the brain´s response to ischemic stroke. However, their phenotypic heterogeneity impedes a holistic understanding of cellular composition early lesion. Here we present single cell resolution transcriptomics dataset acute infarction. Oligodendrocyte lineage cells and astrocytes range among most transcriptionally perturbed populations exhibit infarction- subtype-specific molecular signatures. Specifically, find infarction restricted proliferating oligodendrocyte precursor (OPCs), mature oligodendrocytes reactive astrocytes, exhibiting transcriptional commonalities in injury. OPCs are involved shared immuno-glial cross talk with stroke-specific myeloid cells. Within perilesional zone, osteopontin positive accumulate close proximity CD44

Язык: Английский

Процитировано

11

Interleukin 13 promotes long-term recovery after ischemic stroke by inhibiting the activation of STAT3 DOI Creative Commons
Di Chen, Jiaying Li, Yichen Huang

и другие.

Journal of Neuroinflammation, Год журнала: 2022, Номер 19(1)

Опубликована: Май 16, 2022

Microglia/macrophages are activated after cerebral ischemic stroke and can contribute to either brain injury or recovery by polarizing microglia/macrophage into distinctive functional phenotypes with pro- anti-inflammatory properties. Interleukin-13 (IL-13) is an cytokine that regulates polarization toward phenotype. However, it not clear whether IL-13 beneficial long-term the underlying molecular mechanism(s) remain unknown. Thus, we examined effect of on in mice transient middle artery occlusion model (tMCAO).tMCAO was induced adult male C57BL/6J mice. (60 μg/kg) administered intranasally starting 2 h continued for seven consecutive days. Sensorimotor function, spatial learning memory as well infarct volume were assessed up 35 days stroke. White matter integrity evaluated electrophysiology, immunofluorescence staining, transmission electron microscopy. Microglia/macrophage activation using staining quantitative real-time polymerase chain reaction. Changes immune cells periphery, expression receptors different detected flow cytometry. Primary neuron/microglia co-cultures a STAT3 inhibitor used mechanistic studies.Post-treatment improved neurofunctional decreased tissue atrophy Intranasal delivery enhanced structural white Furthermore, neuroprotection afforded administration due direct neurons, but indirectly regulating phenotype microglia/macrophages. treatment also had no peripheral cells. Mechanistically, outcome promoting microglia/macrophages at least partially inhibiting phosphorylation STAT3.IL-13 promotes repair improves outcomes modulating via inhibition phosphorylation.

Язык: Английский

Процитировано

39

Signaling pathways in brain ischemia: Mechanisms and therapeutic implications DOI

Wen Lin,

Xiaosu Zhao, Jiawen Cheng

и другие.

Pharmacology & Therapeutics, Год журнала: 2023, Номер 251, С. 108541 - 108541

Опубликована: Окт. 1, 2023

Язык: Английский

Процитировано

23