Regulation of microglial activation by progranulin through the NF-κB pathway in subarachnoid hemorrhage and its effect on white matter injury

Subarachnoid hemorrhage (SAH) is a severe cerebrovascular condition commonly associated with white matter injury and subsequent cognitive dysfunction. Emerging evidence suggests that progranulin (PGRN) is involved in neuroinflammation regulation and myelin integrity maintenance. This study aimed to investigate the role of PGRN in SAH and to elucidate its potential neuroprotective mechanisms. Magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) samples from clinical patients were analyzed, with inflammatory factors measured by enzyme-linked immunosorbent assay (ELISA). In a rat SAH model, myelin basic protein (MBP) and ionized calcium-binding adapter molecule 1 (IBA-1) expression were assessed by Western blotting and immunofluorescence, and transcriptomic analysis was performed to identify gene expression changes. Cognitive function was evaluated using the Morris water maze. Transcriptomic results showed that genes altered after SAH were mainly enriched in pathways related to glial cell differentiation, myelin integrity, and immune regulation. Clinical MRI and CSF findings suggested an association between SAH, inflammation, and cognitive impairment. In animal experiments, increased PGRN expression was associated with reduced brain injury and improved myelin integrity. Behavioral testing indicated that treatment with the PGRN enhancer AL001 shortened escape latency and increased time spent in the target quadrant, suggesting improved cognitive performance. These findings suggest that PGRN may exert neuroprotective effects after SAH by modulating glial activity and maintaining myelin integrity, and that AL001 may represent a potential therapeutic approach for alleviating cognitive dysfunction following SAH.