Multiscale analysis of resolvin D1 biosynthesis and its neuroprotective role in intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is a destructive cerebrovascular disease, whose secondary injury can trigger severe neuroinflammatory responses. Resolvin D1 (RvD1), as an endogenous specific pro-resolving mediator, has been demonstrated to possess significant anti-inflammatory effects. However, how brain networks relate to RvD1 biosynthesis and the therapeutic potential of RvD1 in post-hemorrhagic repair processes within the brain remain unclear.

Serum RvD1 levels were measured at admission and discharge in 40 ICH patients, and their correlation with neurological functional outcomes was analyzed. Combining neuroimaging and Mendelian randomization, we investigated the association between brain network integrity and genetically predicted plasma RvD1 levels. Network pharmacology identified key targets, and an oxyhemoglobin-induced BV2 microglial model validated RvD1's BDNF-dependent anti-inflammatory and anti-apoptotic effects.

Serum RvD1 levels decreased from admission to discharge during recovery, with significant correlation between its changes and neurological improvement. Neuroimaging and MR analysis revealed that brain network integrity is significantly associated with genetically predicted plasma RvD1 levels, partially explaining interindividual prognostic variation. Mechanistically, RvD1 modulates microglial metabolism, alleviates oxidative stress, and promotes anti-inflammatory polarization involving the BDNF/AKT signaling network.

Genetically predicted plasma RvD1 levels correlate with macro-level brain network integrity while simultaneously promoting micro-level neural repair. This approach overcomes limitations of previous single-pathway or static indicator studies, offering novel biomarkers and intervention strategies with predictive and therapeutic potential for ICH.