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Enhanced hippocampal neurogenesis in APP/PS1 mouse model of Alzheimer's disease after implantation of VEGF-loaded PLGA nanospheres


Year of Publication:
Contact PI Name:
Rosa M. Hernandez
Contact PI Affiliation:
Neuroscience Laboratory, Research Center, Hospital Universitario, Spain
E. Herran, R. Pérez-González, M. Igartua, J.L. Pedraz, E. Carro
Primary Reference (PubMED ID):
Funding Source:
Spanish Ministry of Science and Innovation
University of Basque Country
FEDER Funds/European Regional Development Fund (ERDF)
Study Goal and Principal Findings:

During adult life, hippocampus is an important brain region involved in neurogenesis. The generation and cell death of newly generated neuronal cells in this region have critical roles in brain maintenance and alterations in these processes are seen in Alzheimer’s disease (AD). For the purpose of carrying out a neuroregenerative strategy, we propose a novel approach based on the encapsulation of vascular endothelial growth factor (VEGF) in poly (lactic co-glycolic acid) (PLGA) biodegradable nanospheres (NS) administered by craniotomy to stimulate the proliferation of neuronal precursors in a transgenic mouse model of AD. VEGF loaded nanospheres were prepared by double emulsion solvent evaporation technique, obtaining 200 nm nanospheres with a biphasic release profile. After demonstrating their efficacy in the proliferation and differentiation of neuronal cell cultures, in vivo studies were carried out. 3 months after VEGF-NS were implanted directly into the cerebral cortex of APP/Ps1 mice, the determination of BrdU+ cells in the whole hippocampal region and specifically in the dentate gyrus, demonstrated a significantly enhanced cellular proliferation in VEGF-NS treated group. These results were also confirmed showing an increased number of DCX+ and NeuN+ cells. Hence, PLGA-VEGF nanospheres may be a potential strategy to modulate proliferative neuronal progenitors in the hippocampal region, and therefore, provide new insight for future therapeutic approaches in AD.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Protein
Therapeutic Agent:
VEGF-Loaded PLGA Nanospheres
Therapeutic Target:
Vascular Endothelial Growth Factor Receptor (VEGFR)

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Not Reported

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest


Outcome Measured
Outcome Parameters
Cell Proliferation
Neuronal Progenitors
Electron Microscopy
Nanosphere Morphology
Cell Biology
Cell Viability
Cell Proliferation
Neuronal Differentiation