%0 Journal Article 
%A Atienza Navarro, Isabel
%A Marco Delgado, Ángel José del
%A Alves Martinez, Pilar
%A García Pérez, María de los Ángeles
%A Raya Marín, Álvaro
%A Benavente Fernández, Isabel
%A Gil, Carmen
%A Martínez, Ana
%A Lubián López, Simón Pedro
%A García Alloza, Mónica
%T Glycogen Synthase Kinase‑3β Inhibitor VP3.15 Ameliorates Neurogenesis, Neuronal Loss and Cognitive Impairment in a Model of Germinal Matrix‑intraventricular Hemorrhage of the Preterm Newborn
%D 2024
%@ 1868-4483
%U http://hdl.handle.net/10498/31858
%X Advances in neonatology have significantly reduced mortality rates due to prematurity. However, complications of prema-
turity 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-3β (GSK-3β) inhibitor. VP3.15 reduces neuroinflammation and neuronal loss in other neuro-
degenerative 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
%K Preterm newborn
%K Germinal matrix-intraventricular hemorrhage
%K VP3.15
%K Neurodegeneration
%K Neurogenesis
%K Cognition
%~ Universidad de Cádiz