Immunomodulation With Local, Sustained Delivery of Pituitary Adenylate Cyclase Activating Polypeptide Results in Improved Functional Recovery in Stroke-Injured Mice.

ABSTRACT: Following ischemic stroke, astrocytes and microglia become activated and create a hostile microenvironment that can exacerbate brain damage, yet these cells also contribute to tissue regeneration. Pituitary adenylate cyclase activating polypeptide (PACAP) is a promising neuroprotective peptide that modulates microglia toward a pro-reparative phenotype, however, its short half-life in vivo and dose-limited off-target effects have made systemic delivery untenable. Local delivery presents a promising alternative. To this end, we developed a hydrogel-nanoparticle composite for the minimally invasive, local delivery of PACAP to the brain and tested this strategy in chemically-induced, endothelin-1 stroke-injured mice. We demonstrate that prolonged delivery of PACAP improved the physical strengt

SUBMITTER: Ho E 

PROVIDER: S-EPMC12447048 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature