Injection of SDF-1 loaded nanoparticles following traumatic brain injury stimulates neural stem cell recruitment

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Zamproni, Laura N. [UNIFESP]
Mundim, Mayara V. [UNIFESP]
Porcionatto, Marimelia A. [UNIFESP]
des Rieux, Anne
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Recruiting neural stem cell (NSC) at the lesion site is essential for central nervous system repair. This process could be triggered by the local delivery of the chemokine SDF-1. We compared two PLGA formulations for local brain SDF-1 delivery: SDF-1 loaded microspheres (MS) and SDF-1 loaded nanoparticles (NP). Both formulations were able to encapsulate more than 80% of SDF-1 but presented different release profiles, with 100% of SDF-1 released after 6 days for the MS and with 25% of SDF-1 released after 2 weeks for NP. SDF-1 bioactivity was demonstrated by a chemotactic assay. When injected in mouse brain after traumatic brain injury, only SDF-1 nanoparticles induced NSC migration to the damage area. More neuroblasts (DCX+ cells) could be visualized around the lesions treated with NP SDF-1 compared to the other conditions. Rostral migratory stream destabilization with massive migration of DCX+ cell toward the perilesional area was observed 2 weeks after NP SDF-1 injection. Local injection of SDF-1-loaded nanoparticles induces recruitment of NSC and could be promising for brain injury lesion. (C) 2017 Elsevier B.V. All rights reserved.
International Journal Of Pharmaceutics. Amsterdam, v. 519, p. 323-331, 2017.