Local Delivery of BDNF Enables Behavioural Recovery and Tissue Repair in Stroke-Injured Rats

We induced tissue repair following ischemic stroke in rats by delivering brain-derived neurotropic factor (BDNF) directly to the brain. This protein is a potent modulator of plasticity and neuroprotection in the developing and adult central nervous system; however, the therapeutic potential of BDNF has been largely thwarted by its inability to cross the blood brain barrier at an effective concentration. Herein, we demonstrate enhanced acute recovery of forepaw dexterity and enhanced hindlimb function at 7 weeks post-injury by delivering BDNF locally, with sustained release in vivo for up to 21 days. Using an encapsulation-free methodology, BDNF was dispersed in a hydrogel composed of hyaluronan and methyl cellulose (HAMC) with poly(lactic-co-glycolic acid) (PLGA) nanoparticles and this composite was deposited epi-cortically, directly above the stroke lesion. BDNF delivery augmented plasticity, as evidenced by synaptophysin staining in the contralesional hemisphere of BDNF-treated rats, and presence of the...