Vascular Endothelial Growth Factor: Adaptive Changes in the Neuroglialvascular Unit

Abstract

Brain postnatal development is modulated by adaptation and experience. Experience-mediated changes increase neuronal activity leading to increased metabolic demands that involve adaptive changes including ones at the microvascular network. Therefore, vascular environment plays a key role in central nervous system (CNS) development and function in health and disease. Trophic factors are crucial in CNS development and cell survival in adults. They participate in protection and proliferation of neuronal, glial and endothelial cells. Among the most important molecules are: the proangiogenic vascular endothelial growth factor (VEGF), the neurotrophin brain derived neurotrophic factor (BDNF), insulin growth factor (IGF-I) and the glycoprotein erythropoietin (EPO). We propose the term angioglioneurins to define molecules acting on the three components of the neurogliovascular unit. We have previously reported the effects of environmental modifications on the three components of the neurogliovascular unit during the postnatal development. We have also described the main role played by VEGF in the experience-induced postnatal changes. 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.

VEGFR1 and VEGFR2 in Alzheimer’s Disease

“…The expression of VEGFR1 and VEGFR2 by neurons is in keeping with previous evidence of the involvement of VEGF in neurogenesis, neuronal migration and synaptic plasticity [22][23][24][25][26]40]. VEGFR2 was previously identified in astrocytes under hypoxic conditions [63,64], and in a subset of astrocytes in AD [29] and in human post-mortem brain tissue from patients with small vessel disease and controls [65].…”

“…VEGF-A (VEGF) is a pro-angiogenic factor [20,21] that is also involved in neuroprotection, neurogenesis, synaptic plasticity, and modulation of inflammation and astrocyte proliferation [22][23][24][25][26]. It is upregulated in response to hypoxia [27,28] and elevated within hypoperfused cortex and white matter in small vessel disease, vascular dementia and AD [3,[29][30][31][32].…”

VEGF reverts the cognitive impairment induced by a focal traumatic brain injury during the development of rats raised under environmental enrichment

“…These molecules exert effects over all components of the neurogliovascular unit (NVU), such as vessels, neurons and glia, and some authors refer to these molecules as angioglioneurins [1,2]. Vascular Endothelial Growth Factor (VEGF) is the archetypal angioglioneurin and acts on both vascular and neural development.…”

Effect of intracortical vascular endothelial growth factor infusion and blockade during the critical period in the rat visual cortex

“…Our results show that the infusion of VEGF as a neuroprotective strategy produces effects in most of the NVU components: neurons, astrocytes and the vascular network. In this line, molecules like VEGF, that affect both the neural and the vascular cell processes have recently been termed angioneurins (Zacchigna et al, 2008;Lafuente et al, 2012;Argandoñ a et al, 2012).…”