Article (Scientific journals)
Use of liposome-encapsulated estetrol for treatment of neonatal hypoxic-ischemic encephalopathy.
Tskitishvili, Ekaterine; Palazzo, Claudio; Foidart, Jean-Michel et al.
2023In Brain Research, 1809, p. 148369
Peer Reviewed verified by ORBi


Full Text
Tskitishvili-Brain Res 2023.pdf
Publisher postprint (8.32 MB)
Request a copy

All documents in ORBi are protected by a user license.

Send to


Keywords :
Brain; Drug-in cyclodextrin in liposome (DCL) system with E4; Estetrol; Liposome-encapsulated E4; Neonatal HIE; Liposomes; Estrogens; Rats; Animals; Liposomes/metabolism; Liposomes/pharmacology; Estrogens/metabolism; Neurons/metabolism; Estetrol/metabolism; Estetrol/pharmacology; Estetrol/therapeutic use; Hypoxia-Ischemia, Brain/drug therapy; Hypoxia-Ischemia, Brain/metabolism; Hypoxia-Ischemia, Brain; Neurons; Neuroscience (all); Molecular Biology; Neurology (clinical); Developmental Biology; General Neuroscience
Abstract :
[en] Estetrol (E4) is a natural estrogen synthesized only during pregnancy. It has strong neuroprotective and antioxidative activities. The aim of the present study was to define the neuroprotective potency of E4 encapsulated either in liposome (Lipo-E4) or in drug-in cyclodextrin (HP-β-CD) in liposome (DCL) system, and compare them with a single use of E4. In vitro studies were performed in an oxidative stress model of primary hippocampal neuronal cell cultures, followed by the lactate dehydrogenase activity and cell proliferation assays. In vivo studies were conducted by using a model of neonatal hypoxic-ischemic encephalopathy in immature rat pups. Brain samples were studied by (immuno)histochemistry for the detection of survived cells, expression of microtubule-associated protein-2, myelin basic protein, doublecortin and vascular-endothelial growth factor. Concentrations of glial fibrillary acidic protein in blood serum were studied by ELISA. In vitro, cell proliferation was significantly up-regulated in cultures treated either by DCL-E4 or E4 compared to the control cells, whereas DCL-E4 treated cells had significantly higher survival rate than the cells treated by E4 alone. Evaluation of brain samples showed that DCL-E4 and a high dose of E4 alone significantly preserve the grey and the white matter loses, and diminish GFAP expression in blood. Although DCL-E4 and E4 have similar effect on neurogenesis in the hippocampus and the cortex, DCL-E4 treatment significantly up-regulates angiogenesis in the hippocampus compared to a single use of E4. Present work reveals for the first time that liposome-encapsulated E4 might be a better alternative to a single use of E4.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Tskitishvili, Ekaterine  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire
Palazzo, Claudio ;  Université de Liège - ULiège > Département de pharmacie
Foidart, Jean-Michel ;  Université de Liège - ULiège > Département des sciences cliniques
Piel, Géraldine ;  Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Pequeux, Christel  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Language :
Title :
Use of liposome-encapsulated estetrol for treatment of neonatal hypoxic-ischemic encephalopathy.
Publication date :
15 June 2023
Journal title :
Brain Research
Publisher :
Elsevier B.V., Netherlands
Volume :
Pages :
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
Région wallonne [BE]
ULiège - University of Liège [BE]
Fonds Léon Fredericq [BE]
Funding text :
We would like to thank the SPW Economie, Emploi, Recherche of the Walloon Region (DG06-WBHealth project Convention n° 1318039) and the Fondation Léon Frédéricq for financial support.
Available on ORBi :
since 26 June 2023


Number of views
32 (4 by ULiège)
Number of downloads
0 (0 by ULiège)

Scopus citations®
Scopus citations®
without self-citations


Similar publications

Contact ORBi