M_PM_018: VP3.15 RESTORES GREY AND WHITE MATTER ALTERATIONS AND VASCULAR DAMAGE IN A MODEL OF GERMINAL MATRIX-INTRAVENTRICULAR HEMORRHAGE OF PRETERM NEWBORN
Monday, April 28, 2025 1:50 PM to 3:20 PM · 1 hr. 30 min. (Europe/London)
Poster Zone 2
Traditional poster
Germinal Matrix-Intraventricular HemorrhagePreterm NewbornVP3.15
Information
Introduction: Germinal matrix-intraventricular hemorrhage (GM-IVH) results in the worst neurocognitive outcomes of all infants born preterm. There are no successful treatments for GM-IVH. VP3.15 is a glycogen synthase kinase 3β and phosphodiesterase 7 dual inhibitor with neuroprotective activity in neurodegenerative diseases. Specifically, VP3.15 is effective in limiting neurodegeneration, promoting remyelination and maintaining axonal integrity, among others. Therefore, we have assessed the effects of VP3.15 on neuronal and myelination alterations as well as on vascular damage in a murine model of GM-IVH.
Methods & approach for statistical analysis: GM-IVH was induced to P7 CD1 mice by intraventricular infusion of collagenase. Animals were treated with VP3.15 (10 mg/kg/day) i.p., or vehicle for 7 consecutive days. In the short term (P14), ventricle size was measured as well as the presence of periventricular hemorrhages and hemosiderin deposits using a Bruker 9.7T MRI small-animal scanner with T2-weighted fast spin echo sequences. Images were quantified using ITK-SNAP software. Postmortem studies included analysis of neuronal density by NeuN-DAPI staining and the presence of hemorrhages with Prussian blue staining in the periventricular region. Myelin basic protein levels were measured by ELISA. One-way ANOVA was performed for independent samples, followed by Tukey´s b or Tamhane tests as required.
Results: Acute VP3.15 treatment reduced ventricular enlargement and periventricular hemorrhage. Likewise, neuronal compromise in the area surrounding the ventricles where the GM-IVH was induced was ameliorated. In addition, significantly lower white matter volumes and myelin basic protein levels that were found after GM-IVH were restored after treatment with VP3.15. Finally, VP3.15 also decreased the volume of hemosiderin deposits, as well as the presence of hemorrhages in the periventricular zone after GM-IVH.
Conclusions: Our data show that glycogen synthase kinase 3β and phosphodiesterase 7 dual inhibition by VP3.15 reduced not only grey and withe matter alterations, but also decreased GM-IVH induced vascular damage. In summary, our results support the neuroprotective role of VP3.15 in GM-IVH-related pathology.
Methods & approach for statistical analysis: GM-IVH was induced to P7 CD1 mice by intraventricular infusion of collagenase. Animals were treated with VP3.15 (10 mg/kg/day) i.p., or vehicle for 7 consecutive days. In the short term (P14), ventricle size was measured as well as the presence of periventricular hemorrhages and hemosiderin deposits using a Bruker 9.7T MRI small-animal scanner with T2-weighted fast spin echo sequences. Images were quantified using ITK-SNAP software. Postmortem studies included analysis of neuronal density by NeuN-DAPI staining and the presence of hemorrhages with Prussian blue staining in the periventricular region. Myelin basic protein levels were measured by ELISA. One-way ANOVA was performed for independent samples, followed by Tukey´s b or Tamhane tests as required.
Results: Acute VP3.15 treatment reduced ventricular enlargement and periventricular hemorrhage. Likewise, neuronal compromise in the area surrounding the ventricles where the GM-IVH was induced was ameliorated. In addition, significantly lower white matter volumes and myelin basic protein levels that were found after GM-IVH were restored after treatment with VP3.15. Finally, VP3.15 also decreased the volume of hemosiderin deposits, as well as the presence of hemorrhages in the periventricular zone after GM-IVH.
Conclusions: Our data show that glycogen synthase kinase 3β and phosphodiesterase 7 dual inhibition by VP3.15 reduced not only grey and withe matter alterations, but also decreased GM-IVH induced vascular damage. In summary, our results support the neuroprotective role of VP3.15 in GM-IVH-related pathology.
Theme
Ageing & neurodegeneration