Abstract
Background
Subarachnoid hemorrhage is associated with high mortality and morbidity rates. In its early stages, the substantial influx of blood into the subarachnoid space triggers excessive activation of microglial cells, which markedly contributes to early brain injury, a pivotal determinant of poor prognosis. Tremella fuciformis polysaccharides, as acidic heteropolysaccharides from the fruiting bodies of Tremella, exhibit robust anti-inflammatory characteristics and a plethora of biological properties. Nonetheless, the impact of TFPS on EBI subsequent to SAH has yet to be documented, and the elucidation of its underlying molecular mechanisms remains elusive. The objective of this study is to elucidate the effects and potential mechanisms of TFPS on EBI in SAH.
Methods
We used in vivo and in vitro models to study TFPS effects on microglia post-SAH. Network pharmacology analysis predicted TFPS targets and intervention pathways. These predictions were subsequently corroborated through flow cytometry, Western blotting, Immunofluorescent, Enzyme-Linked Immunosorbent Assay, and Quantitative real‑time polymerase chain reaction, both in vivo and in vitro.
Results
After 24 hours, TFPS-treated mice showed improved neurological function and reduced cerebral edema post-SAH. TFPS reversed microglial activation, enhanced phagocytic capability, and reduced neuronal apoptosis. Network pharmacology identified KDR as a potential target, with the P38 MAPK pathway as the downstream pathway. TFPS attenuated KDR expression, inhibited the P38 MAPK/NF-κB pathway, reduced inflammatory cytokine expression, and improved microglial phagocytic capacity post-SAH.
Conclusion
This investigation posits that TFPS may ameliorate EBI in SAH, potentially via the regulation of the KDR-mediated P38 MAPK/NF-κB pathway and phagocytic function.