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Glycogen Synthase Kinase-3ß Inhibitor VP3.15 Ameliorates Neurogenesis, Neuronal Loss and Cognitive Impairment in a Model of Germinal Matrix-intraventricular Hemorrhage of the Preterm Newborn.
Atienza-Navarro, Isabel; Del Marco, Angel; Alves-Martinez, Pilar; Garcia-Perez, Maria de Los Angeles; Raya-Marin, Alvaro; Benavente-Fernandez, Isabel; Gil, Carmen; Martinez, Ana; Lubian-Lopez, Simon; Garcia-Alloza, Monica.
Afiliação
  • Atienza-Navarro I; Division of Physiology, School of Medicine, University of Cadiz, C/Dr. Marañon 3, 3rd Floor, 11002, Cadiz, Spain.
  • Del Marco A; Biomedical Research and Innovation Institute of Cadiz (INiBICA) Research Unit, Puerta del Mar University Hospital, Cadiz, Spain.
  • Alves-Martinez P; Division of Physiology, School of Medicine, University of Cadiz, C/Dr. Marañon 3, 3rd Floor, 11002, Cadiz, Spain.
  • Garcia-Perez MLA; Biomedical Research and Innovation Institute of Cadiz (INiBICA) Research Unit, Puerta del Mar University Hospital, Cadiz, Spain.
  • Raya-Marin A; Division of Physiology, School of Medicine, University of Cadiz, C/Dr. Marañon 3, 3rd Floor, 11002, Cadiz, Spain.
  • Benavente-Fernandez I; Biomedical Research and Innovation Institute of Cadiz (INiBICA) Research Unit, Puerta del Mar University Hospital, Cadiz, Spain.
  • Gil C; Division of Physiology, School of Medicine, University of Cadiz, C/Dr. Marañon 3, 3rd Floor, 11002, Cadiz, Spain.
  • Martinez A; Biomedical Research and Innovation Institute of Cadiz (INiBICA) Research Unit, Puerta del Mar University Hospital, Cadiz, Spain.
  • Lubian-Lopez S; Area of Pediatrics, Department of Child and Mother Health and Radiology, School of Medicine, University of Cadiz, Cadiz, Spain.
  • Garcia-Alloza M; Section of Neonatology, Division of Pediatrics, Puerta del Mar University Hospital, Avda. Ana de Viya sn, 11007, Cadiz, Spain.
Transl Stroke Res ; 2024 Jan 17.
Article em En | MEDLINE | ID: mdl-38231413
ABSTRACT
Advances in neonatology have significantly reduced mortality rates due to prematurity. However, complications of prematurity have barely changed in recent decades. Germinal matrix-intraventricular hemorrhage (GM-IVH) is one of the most severe complications of prematurity, and these children are prone to suffer short- and long-term sequelae, including cerebral palsy, cognitive and motor impairments, or neuropsychiatric disorders. Nevertheless, GM-IVH has no successful treatment. VP3.15 is a small, heterocyclic molecule of the 5-imino-1,2,4-thiadiazole family with a dual action as a phosphodiesterase 7 and glycogen synthase kinase-3ß (GSK-3ß) inhibitor. VP3.15 reduces neuroinflammation and neuronal loss in other neurodegenerative disorders and might ameliorate complications associated with GM-IVH. We administered VP3.15 to a mouse model of GM-IVH. VP3.15 reduces the presence of hemorrhages and microglia in the short (P14) and long (P110) term. It ameliorates brain atrophy and ventricle enlargement while limiting tau hyperphosphorylation and neuronal and myelin basic protein loss. VP3.15 also improves proliferation and neurogenesis as well as cognition after the insult. Interestingly, plasma gelsolin levels, a feasible biomarker of brain damage, improved after VP3.15 treatment. Altogether, our data support the beneficial effects of VP3.15 in GM-IVH by ameliorating brain neuroinflammatory, vascular and white matter damage, ultimately improving cognitive impairment associated with GM-IVH.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article