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© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Exogenous neuroprotective protein neuroglobin (Ngb) cannot cross the blood–brain barrier. To overcome this difficulty, we synthesized hyaluronate nanoparticles (NPs), able to deliver Ngb into the brain in an animal model of stroke (MCAO). These NPs effectively reached neurons, and were microscopically identified after 24 h of reperfusion. Compared to MCAO non-treated animals, those treated with Ngb-NPs showed survival rates up to 50% higher, and better neurological scores. Tissue damage improved with the treatment, but no changes in the infarct volume or in the oxidative/nitrosative values were detected. A proteomics approach (p-value < 0.02; fold change = 0.05) in the infarcted areas showed a total of 219 proteins that significantly changed their expression after stroke and treatment with Ngb-NPs. Of special interest, are proteins such as FBXO7 and NTRK2, which were downexpressed in stroke, but overexpressed after treatment with Ngb-NPs; and ATX2L, which was overexpressed only under the effect of Ngb. Interestingly, the proteins affected by the treatment with Ngb were involved in mitochondrial function and cell death, endocytosis, protein metabolism, cytoskeletal remodeling, or synaptic function, and in regenerative processes, such as dendritogenesis, neuritogenesis, or sinaptogenesis. Consequently, our pharmaceutical preparation may open new therapeutic scopes for stroke and possibly for other neurodegenerative pathologies.

Details

Title
Biological Implications of a Stroke Therapy Based in Neuroglobin Hyaluronate Nanoparticles. Neuroprotective Role and Molecular Bases
Author
María Ángeles Peinado 1   VIAFID ORCID Logo  ; Ovelleiro, David 1   VIAFID ORCID Logo  ; del Moral, María Luisa 1 ; Hernández, Raquel 1 ; Martínez-Lara, Esther 1 ; Siles, Eva 1   VIAFID ORCID Logo  ; Pedrajas, José Rafael 1   VIAFID ORCID Logo  ; García-Martín, María Luisa 2   VIAFID ORCID Logo  ; Caro, Carlos 2   VIAFID ORCID Logo  ; Peralta, Sebastián 3 ; Morales, María Encarnación 3 ; Ruiz, María Adolfina 3 ; Blanco, Santos 1   VIAFID ORCID Logo 

 Department of Experimental Biology, Campus de Las Lagunillas s/n, University of Jaén, Building B3, 23071 Jaen, Spain; [email protected] (D.O.); [email protected] (M.L.d.M.); [email protected] (R.H.); [email protected] (E.M.-L.); [email protected] (E.S.); [email protected] (J.R.P.) 
 BIONAND-Centro Andaluz de Nanomedicina y Biotecnología, Junta de Andalucía, Universidad de Málaga, Parque Tecnológico de Andalucía, 29590 Malaga, Spain; [email protected] (M.L.G.-M.); [email protected] (C.C.) 
 Department of Pharmacy and Pharmaceutical Technology, Campus de Cartuja s/n, School of Pharmacy, University of Granada, 18071 Granada, Spain; [email protected] (S.P.); [email protected] (M.E.M.); [email protected] (M.A.R.) 
First page
247
Publication year
2022
Publication date
2022
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2618239068
Copyright
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.