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MicroRNA-124-loaded nanoparticles increase survival and neuronal differentiation of neural stem cells in vitro but do not contribute to stroke outcome in vivo

Saraiva, Cláudia LU ; Talhada, Daniela LU ; Rai, Akhilesh ; Ferreira, Raquel ; Ferreira, Lino ; Bernardino, Liliana and Ruscher, Karsten LU (2018) In PLoS ONE 13(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,... (More)

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.

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Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
13
issue
3
article number
e0193609
publisher
Public Library of Science
external identifiers
  • pmid:29494665
  • scopus:85042940584
ISSN
1932-6203
DOI
10.1371/journal.pone.0193609
language
English
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yes
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ac24aad5-d8c7-4426-b83a-36b589dcba38
date added to LUP
2018-03-19 10:40:49
date last changed
2020-10-20 03:12:03
@article{ac24aad5-d8c7-4426-b83a-36b589dcba38,
  abstract     = {<p>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.</p>},
  author       = {Saraiva, Cláudia and Talhada, Daniela and Rai, Akhilesh and Ferreira, Raquel and Ferreira, Lino and Bernardino, Liliana and Ruscher, Karsten},
  issn         = {1932-6203},
  language     = {eng},
  month        = {03},
  number       = {3},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  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},
  url          = {http://dx.doi.org/10.1371/journal.pone.0193609},
  doi          = {10.1371/journal.pone.0193609},
  volume       = {13},
  year         = {2018},
}