Cranial photo-immunologic regulation along the skull-meninges-brain axis for promoting recovery from ischemic brain injury
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ABSTRACT:
PROVIDER: PRJNA1062428 | ENA |
REPOSITORIES: ENA
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Project description:Stroke involves in the interaction between central and peripheral immune systems. Skull bone marrows serve as reservoirs for immune cells in brain borders, and can rapidly respond to perturbations in the brain environment. Hence, targeting the skull bone marrow to modulate neuroimmune communications along the calvaria-meninges-brain axis would potentially improve stroke prognosis. Here, we successfully achieved cranial immunomodulation via ultraviolet (UV) irradiation of the interparietal region, which was characterized by rich marrow cavities and channels connecting the skull and meninges. Utilizing the recently-developed long-term clearing cranial window that ensured the integrity of skull, we discovered that the cranial photo-immunologic regulation (CPR) could promote cerebrovascular regeneration and aid in neurovascular repair post ischemic stroke. Single-cell transcriptome analysis revealed that meninge could be a crucial neuroimmune interface for ischemic stroke-induced immune responses. And, CPR could restore the stroke-induced alterations in cellular gene expression, especially meningeal B cells. Further we demonstrated that CPR could effectively alleviate the excessive suppression of meningeal B cell activation caused by ischemic stroke. This work opens avenues for immunoregulation through the skull-meninges-brain axis and provides valuable insights for immunomodulatory therapies in brain diseases.
2024-04-18 | GSE252774 | GEO
Project description:Stroke involves in the interaction between central and peripheral immune systems. Skull bone marrows serve as reservoirs for immune cells in brain borders, and can rapidly respond to perturbations in the brain environment. Hence, targeting the skull bone marrow to modulate neuroimmune communications along the calvaria-meninges-brain axis would potentially improve stroke prognosis. Here, we successfully achieved cranial immunomodulation via ultraviolet (UV) irradiation of the interparietal region, which was characterized by rich marrow cavities and channels connecting the skull and meninges. Utilizing the recently-developed long-term clearing cranial window that ensured the integrity of skull, we discovered that the cranial photo-immunologic regulation (CPR) could promote cerebrovascular regeneration and aid in neurovascular repair post ischemic stroke. Single-cell transcriptome analysis revealed that meninge could be a crucial neuroimmune interface for ischemic stroke-induced immune responses. And, CPR could restore the stroke-induced alterations in cellular gene expression, especially meningeal B cells. Further we demonstrated that CPR could effectively alleviate the excessive suppression of meningeal B cell activation caused by ischemic stroke. This work opens avenues for immunoregulation through the skull-meninges-brain axis and provides valuable insights for immunomodulatory therapies in brain diseases.
2024-04-18 | GSE254550 | GEO
Project description:Cranial photo-immunologic regulation along the skull-meninges-brain axis for promoting recovery from ischemic brain injury
| PRJNA1071029 | ENA
Project description:Skull and vertebral bone marrow are myeloid reservoirs for meninges and CNS parenchyma
| PRJNA675284 | ENA
Project description:The meninges are densely innervated by nociceptive sensory neurons that mediate pain and headache. How pain and neuro-immune interactions impact meningeal host defenses is unclear. Bacterial meningitis causes life-threatening infections of the meninges and central nervous system (CNS), affecting over one million people a year. Here we find that Nav1.8+ neuron signaling to immune cells in the meninges via the neuropeptide calcitonin gene-related peptide (CGRP) exacerbates bacterial meningitis. Nociceptor ablation reduced meningeal and brain invasion by two bacterial pathogens: Streptococcus pneumoniae and Streptococcus agalactiae. S. pneumoniae activated nociceptors via Pneumolysin to release CGRP, which acts through its receptor RAMP1 on meningeal macrophages to inhibit chemokine expression, neutrophil recruitment and antimicrobial defenses. Macrophage-specific RAMP1 deficiency or blockade of RAMP1 signaling enhanced immune responses and bacterial clearance in meninges and brain. Therefore, targeting a neuro-immune axis in the meninges can enhance host defenses and may be a potential treatment for bacterial meningitis.
2022-12-23 | GSE221681 | GEO
Project description:The bone marrow in the skull is important for shaping immune responses in the brain and meninges, but its molecular makeup in comparison to other bones in mice and humans remains unclear. Here, we show that the skull has the most distinct transcriptomic profile compared to other bones in states of health and injury, characterized by a late-stage neutrophil phenotype. In humans, proteome analysis reveal that the skull marrow is the most distinct, with differentially expressed neutrophil-related pathways and a unique synaptic protein signature. 3D imaging demonstrates the structural and cellular details of human skull-meninges connections compared to veins. Lastly, using TSPO-PET imaging, we show that the skull bone marrow reflects inflammatory brain responses with a disease-specific spatial distribution in patients with various neurological disorders. The unique molecular profile, anatomical, and functional connections of the skull show its potential as a new site for diagnosing, monitoring, and treating brain diseases.
2023-07-15 | GSE192616 | GEO
Project description:Background: Previous study showed that stroke may be a potential first sign of neoplasia. But the relationship between them remains unclear. Besides, ischemic stroke is a complex brain disease, which involves cell death or complex immune regulation. Thus, it is necessary to reveal the association of tumor immune microenvironment and cell death with ischemic stroke. Methods: Here, a photothrombosis-induced ischemic injury models of brain and skull was established. We compared and analyzed the pattern of gene expression profile between brain and skull after ischemic injury by transcriptome analysis. Further, we investigated the enrichment of relevant differential genes in cancer pathways and cell death pathways, and analyzed changes in the immune microenvironment after ischemic injury. Moreover, the pan-cancer genomic and prognosis analysis of ischemic injury related gene set were performed. Results: The results showed that the gene expression patterns were different in temporal and spatial locations after ischemic injury. We found that the effect on the transcriptome of the brain after skull ischemic injury was particularly large, but it could be recovered in a short period, while the effect on the skull after brain ischemic injury was long-lasting. The expression of genes related to ischemic injury is also associated with cell death and cancer hallmark pathways. In addition, changes in the abundance of immune cells indicate that brain ischemic injury may disrupt its immune microenvironment for a longer time, while skull can better balance the stability of immune microenvironment. Moreover, the brain ischemic injury-related gene sets are highly correlated with a variety of tumors, especially GBM, KIRC, LGG and UVM after stroke have a greater risk of death. Conclusion: This study gives us a new understanding of the role of the skull in brain ischemic injury, and reveals the association of tumor immune microenvironment and cell death with ischemic stroke.
2022-09-25 | GSE213429 | GEO
Project description:The central nervous system (CNS) is ensheathed by the meninges and cerebrospinal fluid. Recent findings suggest complex immunological functions of these CNS-associated border tissues. Unlike myeloid lineage cells, lymphocytes in border compartments have been largely disregarded in previous studies. Based on single cell transcriptomics, we here identified a highly location-specific composition and expression profile of tissue-resident leukocytes in every border compartment. Only the dura layer of the meninges contained a large population of B cells under homeostatic conditions in multiple species. Murine dura B cells exhibited slow turnover, long-term tissue residency and matured in experimental neuroinflammation. The dura also contained B lineage progenitors at the pro-B cell stage unexpected outside of bone marrow, without direct influx from the periphery or the skull bone marrow. This identifies the dura as an unexpected site of B cell residence and potentially development in homeostasis and neuroinflammation.
2021-05-01 | GSE165153 | GEO
Project description:The meninges of the brain are an important component of neuroinflammatory response. Diverse immune cells move from the calvaria marrow into the dura mater via recently discovered skull-meninges connections (SMCs). However, how the calvaria bone marrow is different from the other bones and whether and how it contributes to human diseases remain unknown. Using multi-omics approaches and whole mouse transparency we reveal that bone marrow cells are highly heterogeneous across the mouse body. The mouse calvaria and the human skull harbors the most distinct molecular signature with hundreds of differentially expressed genes and proteins when compared to other bones. Our study indicates that the calvaria is more than a physical barrier, and its immune cells may present new ways to control brain pathologies.
2023-07-29 | PXD041665 | Pride
Project description:Diverse immune cells move from the calvaria marrow into the dura mater via recently discovered skull-meninges connections (SMCs). Yet, how the calvaria bone marrow is different from the other bones and whether it plays a special role in human diseases remain unknown. Using multi-omics approaches and whole mouse transparency we reveal that bone marrow cells are highly heterogeneous across the mouse body. The calvaria harbors the most distinct molecular signature with hundreds of differentially expressed genes and proteins. Acute brain injury induces skull-specific outcomes including increased calvaria cell numbers. Moreover, TSPO-PET imaging of stroke, dementia and multiple sclerosis patients demonstrate increased inflammation in the human skull, mirroring the underlying brain inflammation.
2024-01-17 | PXD030250 | Pride