NAD-Dependent Protein Deacetylase Sirtuin-1 Mediated Mitophagy Regulates Early Brain Injury After Subarachnoid Hemorrhage

Background: This study focuses on the role of SIRT1 in neuroinflammation caused by early brain injury (EBI) after subarachnoid hemorrhage (SAH), and explores its mechanism in Mitophagy after SAH.

Methods: C57BL/6J mice and primary microglia SAH in vivo and in vitro models were constructed to explore the expression level of SIRT1 in neuroinflammation after SAH. Subsequently, the brain edema content, blood-brain barrier (BBB) damage and neurological function scores of the mice were observed after using the SIRT1 Inhibitor EX-527. q-PCR and Western blot were used to detect relevant genes and proteins, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of IL-6, IL-1β, and TNF-α inflammatory factors. Immunofluorescence staining was used to observe the positive level of SIRT1 and the degree of mitochondria-lysosome fusion, and transmission electron microscopy was used to observe mitochondrial damage and autophagosome levels.

Results: In in vivo and in vitro experiments, we found that SIRT1 expression increased after SAH, and neurological deficits, brain edema, and blood-brain barrier damage after SAH were aggravated. Inhibiting SIRT1 further aggravates the aforementioned damage. In addition, EX-527 can also inhibit the level of Mitophagy and aggravate neuroinflammation after SAH.

Conclusion: Our results indicated that SIRT1 promotes Mitophagy and alleviates neuroinflammation after SAH.

SIRT1; early brain injury; mitophagy; subarachnoid hemorrhage.