DENDRITIC NANOSTRUCTURES SUPPRESS INFLAMMATION IN A MODEL OF ISCHEMIC STROKE

Stroke is the second leading cause of death globally, with ischemic events comprising ~60%. They occur when arterial occlusion deprives the brain of oxygen and glucose, causing extensive cell damage and death. The only approved treatment, tissue plasminogen activator, dissolves blood clots but does not address the neuroinflammation that worsens the injury. To address this, we investigated a nanostructure with demonstrated potent anti-inflammatory properties named dendritic polyglycerol sulfate (dPGS). We hypothesize that dPGS promotes an anti-inflammatory environment in a stroke model in our mouse organotypic hippocampal slices, a brain region crucial for cognition and highly vulnerable to ischemic injury. These slices were first treated with dPGS, then ischemia-like conditions were induced through an oxygen-glucose deprivation (OGD) treatment. Microglial uptake, morphology, and the dendritic spine structure of pyramidal cells were assessed by immunohistochemistry, while cytokine release was quantified using ELISA. We find that microglia internalized dPGS and that both OGD treatment and dPGS altered microglial morphology. Additionally, dPGS increased the levels of cytokines linked with anti-inflammatory signaling (IL-10 and IL-33) and mitigated the dematuration of dendritic spines observed in OGD-treated slices. Together, these findings suggest that dPGS modulates microglial responses, promotes a protective anti-inflammatory environment, and preserves dendritic spine integrity under OGD, highlighting its potential as a complementary ischemic stroke therapy.