Neural repair by NT3-chitosan via enhancement of endogenous neurogenesis after adult focal aspiration brain injury.

ABSTRACT

The latent regenerative potential of endogenous neural stem/progenitor cells (NSCs) in the adult mammalian brain has been postulated as a likely source for neural repair. However, the inflammatory and inhibitory microenvironment after traumatic brain injury (TBI) prohibits NSCs from generating new functional neurons to restore brain function. Here we report a biodegradable material, chitosan, which, when loaded with neurotrophin-3 (NT3) and injected into the lesion site after TBI, effectively engaged endogenous NSCs to proliferate and migrate to the injury area. NSCs differentiate and mature into functional neurons, forming nascent neural networks that further integrate into existing neural circuits to restore brain function. Three main actions of NT3-chitosan, i.e., pro-neurogenesis, anti-inflammation, and pro-revascularization, elicit significant regeneration after TBI. Our study suggests that through creating an optimal microenvironment, endogenous NSCs are capable of executing neural repair, thus widening the therapeutic strategies to treat TBI and perhaps stroke or other neurological conditions.