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Cranial Photomodulation Reshapes Brain Border Immunity and Promotes Recovery After Stroke

ABSTRACT: The skull bone marrow represents a targetable neuroimmune interface adjacent to the brain borders with the potential to improve stroke outcomes. Here, we identified the skull as a highly responsive immune niche and developed a cranial photo-immunologic regulation (CPR) strategy using low-dose, narrow-band medical UVB. Targeted irradiation of the interparietal region reshapes brain border immune crosstalk, effectively promoting repair and functional recovery after ischemic injury. Mechanistically, UVB-based CPR reverses stroke-induced suppression of meningeal B cell activation, contributing to restoring brain border immune homeostasis. Depletion of meningeal B cells further demonstrates that these cells are required for the therapeutic effects of CPR. These findings establish the skull as an actionable target for neuroimmune modulation along the skull–meninges–brain axis and provide a potentially transformative strategy for treating neurological disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE254550 | GEO | 2024/04/18

REPOSITORIES: GEO

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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.

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Cranial Photomodulation Reshapes Brain Border Immunity and Promotes Recovery After Stroke

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