Abstract
Microglia-mediated neuroinflammatory response in the early brain injury after subarachnoid hemorrhage (SAH) has been reported to have an impact on progress, and the mechanism is not completely understood. Here, we performed genome-wide transcriptome analysis of microglia purified from damaged hemisphere of adult mice at 3 days after SAH or sham operation. Robust transcriptional changes were observed between SAH-induced and healthy microglia, indicating rapid activation of microglia after suffering from SAH. We identified 1576 differentially expressed genes (DEGs; 928 upregulated and 648 downregulated) in SAH-induced microglia compared with sham microglia, representing a strong alteration of the genome (6.85% of total ∼23,000 genes). Functional enrichment of these DEGs indicated that cell division, inflammatory response, cytokine production, and leukocyte chemotaxis were strongly activated in SAH-induced microglia. Moreover, we identified and proved that the TLR2/IRF7 signaling axis was involved in the regulation of this microglia-mediated inflammation in SAH mice by performing flow cytometry and immunofluorescence. Together, these results provided a perspective of microglia-mediated neuroinflammatory response in the early stage of SAH and might give a new therapeutic target for SAH.
Highlights
Subarachnoid hemorrhage (SAH), which is mainly caused by intracranial aneurysm rupture, is a severe subtype of stroke with high mortality, disability, and poor outcomes (Macdonald and Schweizer, 2017)
We explored the functional implications of microglia in response to subarachnoid hemorrhage (SAH) and found that the microglia involved in neuroinflammation may be regulated by the Toll-like receptor 2 (TLR2)/Interferon regulatory factor 7 (IRF7) signaling pathway
We examined the GO terms related to “cellular response” and found that response to stimulus and response to cytokines were enriched in post-SAH microglia (Figure 5A)
Summary
Subarachnoid hemorrhage (SAH), which is mainly caused by intracranial aneurysm rupture, is a severe subtype of stroke with high mortality, disability, and poor outcomes (Macdonald and Schweizer, 2017). It accounts for 5% of strokes and has an annual incidence of 6–10 cases per 100,000 persons (Amodio et al, 2020; Macdonald and Schweizer, 2017). The main resident immune cells in the central nervous system (CNS), is the most significant mediator in neuroinflammation. They constantly surveil the microenvironment and respond to damage and pathogens, acting as double-edged swords in different pathological states (Soulet and Rivest, 2008; Liu et al, 2019)
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