VEGF: once regarded as a specific angiogenic factor, now implicated in neuroprotection

Abstract

Both blood vessels and nerves are guided to their target. Vascular endothelial growth factor (VEGF)A is a key signal in the induction of vessel growth (a process termed angiogenesis). Though initial studies, now a decade ago, indicated that VEGF is an endothelial cell-specific factor, more recent findings revealed that VEGF also has direct effects on neural cells. Genetic studies showed that mice with reduced VEGF levels develop adult-onset motor neuron degeneration, reminiscent of the human neurodegenerative disorder amyotrophic lateral sclerosis (ALS). Additional genetic studies confirmed that VEGF is a modifier of motor neuron degeneration in humans and in SOD1(G93A) mice--a model of ALS. Reduced VEGF levels may promote motor neuron degeneration by limiting neural tissue perfusion and VEGF-dependent neuroprotection. VEGF also affects neuron death after acute spinal cord or cerebral ischemia, and has also been implicated in other neurological disorders such as diabetic and ischemic neuropathy, nerve regeneration, Parkinson's disease, Alzheimer's disease and multiple sclerosis. These findings have raised growing interest in assessing the therapeutic potential of VEGF for neurodegenerative disorders.

NF-κB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1α

“…This may have been due to defective production of VEGF, a cytokine with anti-inflammatory properties that has been shown to promote tissue repair 23 . VEGF is also a potent neuroprotective factor 24 whose decreased production may potentiate hypoxia-induced neuronal damage and thereby augment astrocyte activation. This situation may be akin to a loss of IKK-b in intestinal epithelial cells, which has previously been found to exacerbate ischaemic damage to the intestinal mucosa 25 .…”

Interactions of primary neuroepithelial progenitor and brain endothelial cells: distinct effect on neural progenitor maintenance and differentiation by soluble factors and direct contact

“…[5][6][7][8][9][10][11][12][13][14][15][16]. This method utilizes a mild trypsinization of embryonic brain that permits the sieve separation of neural cells and the subsequent liberation of EC from cerebral vessels with a gentle collagenase/dispase treatment.…”

“…Recently there has been much interest in the similarities between development of the vascular system and nervous system and particularly in the influences of neuroepithelial cells on vascular EC and vice versa [2][3][4][5][6][7]. For example in the developing brain, neuroepithelial cells in the ventricular zone produce vascular endothelial growth factor (VEGF), which attracts vessel growth into the brain [8].…”

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

“…In pathological conditions, VEGFR mediates an antiapoptotic effect through Phosphoinositide 3-kinase (PI3K)-dependent signaling pathways that promote the survival of endothelial cells induced by VEGF (Jin et al, 2000(Jin et al, , 2001Geretti et al, 2008) and is related to the blood-brain barrier (BBB) opening in brain injury Lafuente et al, 2006;Ortuzar et al, 2010). A neuroprotective role for VEGF via VEGFR-2 has also been described (Oosthuyse et al, 2001;Storkebaum et al, 2004;Moser and Humpel, 2005;Ortuzar et al, 2011), which occurs via the PI3k/Akt and the mitogen-activated protein kinase/ERK kinase/extracellular signal-regulated protein kinase (MEK/ERK) pathways (Wick et al, 2002;Kaya et al, 2005).…”