http://www.tandfonline.com/doi/abs/10.1080/10717544.2016.1199609
- DOI:
- 10.1080/10717544.2016.1199609
- Received: 15 May 2016
- Accepted: 7 Jun 2016
- Accepted author version posted online: 08 Jun 2016
Published online: 08 Jun 2016
Abstract
Currently,
traumatic brain injury (TBI) is the leading cause of death or of
disabilities in young individuals worldwide. The multi-complexity of its
pathogenesis as well as impermeability of the blood-brain barrier (BBB)
make the drug choice and delivery very challenging. The brain-derived
neurotrophic factor (BDNF) regulates neuronal plasticity, neuronal cell
growth, proliferation, cell survival, and long term memory. However, its
short half-life and low BBB permeability are the main hurdles to be an
effective therapeutic for TBI. Poly(lactic-co-glycolic acid) (PLGA)
nanoparticles coated by surfactant can enable the delivery of a variety
of molecules across the BBB by receptor-mediated transcytosis. This
study examines the ability of PLGA nanoparticles coated with poloxamer
188 (PX) to deliver BDNF into the brain and neuroprotective effects of
BNDF in mice with TBI. C57bl/6 mice were subjected to weight-drop closed
head injuries under anesthesia. Using enzyme-linked immunosorbent
assay, we demonstrated that the intravenous (IV) injection of
nanoparticle-bound BDNF coated by PX (NP-BDNF-PX) significantly
increased BDNF levels in the brain of sham-operated mice (p < 0.001)
and in both ipsi- (p < 0.001) and contralateral (p < 0.001) parts
of brain in TBI mice compared to controls. The present study also showed
using the passive avoidance (PA) test, that IV injection of NP-BDNF-PX
3 hours post-injury prolonged the latent time in mice with TBI thereby
reversing cognitive deficits caused by brain trauma. Finally,
neurological severity score test demonstrated that our compound
efficiently reduced the scores at day 7 after the injury indicating the
improvement of neurological deficit in animals with TBI. This study
shows that PLGA nanoparticles coated with PX effectively deliver BDNF
into the brain, and improve neurological and cognitive deficits in TBI
mice, thereby providing a neuroprotective effect.
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