Brain postnatal development is modulated by experience. Experience-mediated changes increase neuronal activity leading to increased metabolic demands that involve adaptive changes including ones at the microvascular network. Trophic factors are crucial in CNS development and cell survival in adults. We have proposed the term
angioglioneurins to define molecules acting on the three components of the neurogliovascular unit. VEGF is the major angiogenic and vascular permeability factor in health and disease. Our aim was to investigate the effects of intracorticalinfusion of VEGF administration, alone or in combination with other neuroprotective strategies such as environmental enrichment, during the critical visual period.
VEGF was intracortically delivered into middle cortical layers of P18 Long Evans rats. PBS-infused and non-operated animals were used as controls. Various immunopathological analyses were performed to test the effects of the lesion induced by the cannula implantation: Endothelial Barrier Antigen (EBA) for the BBB integrity and GFAP for astroglial response. The effects of environmental enrichment alone or combined with VEGF infusion on spatial memory were tested by the Morris Water Maze at P46.
Decreased vascular permeability was evoked in VEGF-infused rats whilst EBA expression remained constant, suggesting a preserved BBB function. If VEGF was blocked, tissue showed a higher degree of extravasation surrounding the injury.
Environmental enrichment produced a significant cognitive improvement in controls that was paralleled infusing VEGF in standard reared animals. On other hand, PBS infusion did not have any detrimental effect. In contrast, lesion induced by cannula implantation annulled the cognitive improvement by environmental enrichment. Environmental enrichment in VEGF-infused rats did not produce further improvements.
Our results support the role of VEGF as extending beyond vascularization. We conclude that VEGF administration leads to a protective effect in brain structure and cognitive function. Angioglioneurin administration, alone or in combination with other neuroprotective strategies such as environmental enrichment, has been proposed as a non-invasive therapeutic strategy against several CNS diseases.
This work will be presented at the Swiss Society for Neuroscience Annual Meeting, in Zurich on February 3, 2012 and can be reviewed HERE.
