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Combination of intracortically administered VEGF and environmental enrichment enhances brain protection in developing rats

  • Basic Neurosciences, Genetics and Immunology - Original Article
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Abstract

Postnatal development of the visual cortex is modulated by experience, especially during the critical period. In rats, a stable neuronal population is only acquired after this relatively prolonged period. Vascular endothelial growth factor (VEGF) is the most important angiogenic factor and also has strong neuroprotective, neurotrophic and neurogenic properties. Similar effects have been described for rearing in enriched environments. Our aim is to investigate the vascular and neuronal effects of combining VEGF infusion and environmental enrichment on the visual cortex during the initial days of the critical period. Results showed that a small percentage of Cleaved Caspase-3 positive cells colocalized with neuronal markers. The lesion produced by the cannula implantation resulted in decreased vascular, neuronal and Caspase-3 positive cell densities. Rearing under enriched environment was unable to reverse these effects in any group, whereas VEGF infusion alone partially corrected those effects. A higher effectiveness was reached by combining both the procedures, the most effective combination being when enriched-environment rearing was introduced only after minipump implantation. In addition to the angiogenic effect of VEGF, applied strategies also had synergic neuroprotective effects, and the combination of the two strategies had more remarkable effects than those achieved by each strategy applied individually.

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Acknowledgments

This study has been supported by the Gangoiti Foundation, SAIOTEK (Dpt. Industry, Government of the Basque Country) and IT/491/10 (Basque Government). N. Ortuzar is supported by a predoctoral grant (FPU) from the Spanish Ministry of Education. Confocal microscopy analysis was performed at the “Servicio de Microscopia Analítica y de Alta Resolución en Biomedicina” (High Resolution Analytical Microscopy Services for Biomedicine) at the University of the Basque Country.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Neuroscience, Laboratory of Clinical and Experimental Neuroscience (LaNCE), Faculty of Medicine and Odontology, University of the Basque Country UPV/EHU, Barrio Sarriena s/n, E48940, Leioa, Spain

    Naiara Ortuzar, Enrike G. Argandoña, Harkaitz Bengoetxea & José V. Lafuente

  2. Department of Nursing I, University of the Basque Country UPV/EHU, Barrio Sarriena, E48940, Leioa, Spain

    Enrike G. Argandoña

Authors
  1. Naiara Ortuzar
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  2. Enrike G. Argandoña
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  3. Harkaitz Bengoetxea
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  4. José V. Lafuente
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Correspondence to Naiara Ortuzar.

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Ortuzar, N., Argandoña, E.G., Bengoetxea, H. et al. Combination of intracortically administered VEGF and environmental enrichment enhances brain protection in developing rats. J Neural Transm 118, 135–144 (2011). https://doi.org/10.1007/s00702-010-0496-2

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  • DOI: https://doi.org/10.1007/s00702-010-0496-2

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