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Title: MicroRNA-124-loaded nanoparticles increase survival and neuronal differentiation of neural stem cells in vitro but do not contribute to stroke outcome in vivo
Authors: Saraiva, Cláudia
Talhada, Daniela
Rai, Akhilesh 
Ferreira, Raquel
Ferreira, Lino 
Bernardino, Liliana 
Ruscher, Karsten 
Issue Date: 2018
Publisher: Public Library of Science
Project: POCI-01-0145-FEDER-007491 
UID/Multi /00709/2013) 
Swedish Brain Fund 
Crafoord Foundation 
Swedish Research Council, 
Sveriges Stroke RiksfoÈrbundet 
Hans-Christian and Alice Wachtmeister Foundation 
Stiftelsen Sven- Olof Jansons livsverk 
Serial title, monograph or event: PLoS ONE
Volume: 13
Issue: 3
Abstract: There is a high quest for novel therapeutic strategies to enhance recovery after stroke. MicroRNA-124 (miR-124) has been described as neuroprotective and anti-inflammatory molecule. Moreover, miR-124 is a well described enhancer of adult neurogenesis that could offer potentially beneficial effects. Herein, we used miR-124-loaded nanoparticles (miR-124 NPs) to evaluate their therapeutic potential in an in vitro and in vivo model of stroke. For that, neuroprotective and neurogenic responses were assessed in an in vitro model of stroke. Here, we found that miR-124 NPs decreased cell death and improved neuronal differentiation of subventricular zone (SVZ) neural stem cell cultures after oxygen and glucose deprivation. In contrast, intravenous injection of miR-124 NPs immediately after permanent focal ischemia induced by photothrombosis (PT) did not provide a better neurological outcome. In addition, treatment did not affect the number of 5-bromo-2'-deoxyuridine (BrdU)- and doublecortin/BrdU- positive cells in the SVZ at the study endpoint of 14 days after PT. Likewise, the ischemic insult did not affect the numbers of neuronal progenitors in the SVZ. However, in PT mice miR-124 NPs were able to specifically augment interleukin-6 levels at day 2 post-stroke. Furthermore, we also showed that NPs reached the brain parenchyma and were internalized by brain resident cells. Although, promising in vitro data could not be verified in vivo as miR-124 NPs treatment did not improve functional outcome nor presented beneficial actions on neurogenesis or post-stroke inflammation, we showed that our NP formulation can be a safe alternative for drug delivery into the brain.
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0193609
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

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