UNASSIGNED: Drug delivery to the central nervous system is limited by the blood-brain barrier, which can be circumvented by local delivery. In applications of @entity64 therapy, for example, stimulation of endogenous neural stem/progenitor cells (NSPCs) by @entity205 ( @entity9472 ) is promising. However, current strategies rely on high systemic drug doses to achieve small amounts of @entity9472 in the brain tissue, resulting in systemic @entity137 and undesirable global immunosuppression. Herein we describe the efficacy of local @entity9472 delivery to the @entity64 -injured @entity35 brain using an epi-cortically injected hydrogel composed of hyaluronan and methylcellulose (HAMC). @entity9472 was encapsulated in @entity7050 microparticles dispersed in HAMC, allowing for its sustained release over 14days in vivo. Tissue penetration was sufficient to provide sustained @entity9472 delivery to the sub-cortical NSPC niche. In comparison to systemic delivery using an osmotic minipump, HAMC achieved higher @entity9472 concentrations in the brain while significantly reducing drug exposure in other organs. HAMC alone was beneficial in the @entity64 -injured @entity35 brain, significantly reducing the @entity64 volume relative to untreated @entity64 -injured controls. The combination of HAMC and local @entity9472 release increased the number of proliferating cells in the lateral ventricles - the NSPC niche in the adult brain. Thus, we demonstrate a superior method of drug delivery to the @entity35 brain that provides dual benefits of tissue protection and endogenous NSPC stimulation after @entity64 .

Circumventing the blood-brain barrier: Local delivery of @entity205 stimulates stem cells in XXXX -injured @entity35 brain.

@entity9472 :: ('D016572', 'Chemical') :: ['CsA'] @entity64 :: ('MESH:D020521', 'Disease') :: ['stroke infarct', 'stroke'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity205 :: ('MESH:D016572', 'Chemical') :: ['cyclosporin A'] @entity7050 :: ('MESH:C043435', 'Chemical') :: ['poly(lactic-co-glycolic acid)'] @entity35 :: ('10116', 'Species') :: ['rat']
@entity64 :: (MESH:D020521,Disease) :: ['stroke']
