EXPRESS: Activation of GPR17 ameliorates neuroinflammation and improves neurological function via NF-κB pathway in an experimental germinal matrix hemorrhage rat model

Germinal matrix hemorrhage (GMH), a major complication of prematurity, involves severe neuroinflammation leading to neurological deficits. While G protein-coupled receptor 17 (GPR17) is known to modulate neuroinflammation, its therapeutic potential in GMH remains unexplored. This study investigated the anti-inflammatory effects and mechanisms of GPR17 activation in a neonatal rat GMH model induced by collagenase injection. Pre-treatment with the GPR17 agonist MDL-29951 was found to upregulate GPR17, downregulate cleaved Caspase-3, IL-1β, and TNF-α, and reduce apoptosis and glial infiltration at 1 day post-GMH. The treatment also improved neurological function, inhibited IκBα degradation and p65 nuclear translocation, and preserved white matter (WM) integrity. In vitro, GPR17 functioned as a negative regulator of the NF-κB pathway in primary microglia. These results suggest that GPR17 activation alleviates neuroinflammation and improves neurological outcomes after GMH, at least in part through attenuation of the NF‑κB pathway.