A Drug Delivery to Improve Prognosis of Traumatic Brain Injury Mice Through Mouse‐Derived Nerve Growth Factor Coated by a Nanoparticle

Nanoparticle encapsulation markedly increased the amount of mNGF that reached the brain parenchyma relative to conventional administration. Enhanced delivery enabled substantially more exogenous mNGF to traverse the BBB in TBI mice than did uncoated mNGF. The treatment attenuated TBI-induced neuronal apoptosis, up-regulated genes involved in neurogenesis and myelinogenesis, restored glymphatic inflow and outflow, repaired BBB structure and function, and mitigated cognitive deficits. These benefits were abolished by the aquaporin-4 inhibitor TGN-020, indicating that mNGF improves TBI outcome by correcting AQP4 dysfunction. To our knowledge, this is the first demonstration that nanocrystallized mNGF can cross the BBB efficiently after TBI and thereby foster neural repair and functional recovery.