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

  title={VEGF: once regarded as a specific angiogenic factor, now implicated in neuroprotection},
  author={Erik Storkebaum and Diether Lambrechts and Peter Carmeliet},
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… 

Insights into the Mechanisms Involved in Protective Effects of VEGF-B in Dopaminergic Neurons

VEGF-B is explored as a homeostatic protective factor that improves mitochondrial function in the setting of cardiovascular and neurological disease, with a specific focus on dopaminergic neurons in Parkinson's disease.

Vascular endothelial growth factor-A is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury.

It is found that VEGF-A exposure resulted in a dose-dependent reduction in retinal neuron apoptosis and this finding has implications for both neural pathologies and ocular vascular diseases, such as diabetic retinopathy and age-related macular degeneration.

Debate on the various anti-vascular endothelial growth factor drugs

The use of selective anti-VEGF agents such as pegaptanib, which inhibits pathologic V EGF164 and spares all other VEGF isomers, is strongly recommended to preserve retinal neurons in the long term, especially in the context of ischemic retinal diseases.

Vascular and neuronal effects of VEGF in the nervous system: implications for neurological disorders.

A challenge for the future is to unravel to what extent the effect of VEGF in these disorders relates to its angiogenic activity or direct neurotrophic effect.

Vascular endothelial growth factor protects spinal cord motoneurons against glutamate‐induced excitotoxicity via phosphatidylinositol 3‐kinase

It is indicated that VEGF has neuroprotective effects in rat spinal cord against chronic glutamate excitotoxicity by activating the PI3‐K/Akt signal transduction pathway and the hypothesis of the potential therapeutic effects of VEGf in the prevention of motoneuron degeneration in human ALS is reinforced.

Roles of Vascular Endothelial Growth Factor in Amyotrophic Lateral Sclerosis

VEGF-B, presenting a single safety profile, protects motor neurons from degeneration in ALS animal models and, therefore, it will be particularly interesting to test its effects in ALS patients.

VEGF 165 b is an endogenous neuroprotective splice isoform of VEGF-A in vivo and in vitro .

Recombinant human and rat VEGF 165 b exerted neuroprotective effects on several different neuronal types exposed to different insults, including glutamatergic excitotoxicity in hippocampal neurons, chemotherapy induced cytotoxicity of dorsal root ganglion cells and retinal ganglions in rat retinal ischemia-reperfusion injury in vivo.

Neurovascular unit and the effects of dosage in VEGF toxicity: role for oxidative stress and thrombin.

The data show that microvessels isolated from AD patients secrete significantly higher levels of VEGF compared to control-derived vessels, and caution is warranted prior to implementation of V EGF as a therapeutic in the brain.



Neuroprotective effects of vascular endothelial growth factor (VEGF) upon dopaminergic neurons in a rat model of Parkinson's disease

VEGF was found to be neuroprotective against cell death of primary E14 murine ventral mesencephalic neurons induced by 6‐hydroxydopamine (6‐OHDA) treatment in vitro and this results support a potential neuroProtective role for VEGF in the treatment of Parkinson's disease.

Vascular endothelial growth factor: direct neuroprotective effect in in vitro ischemia.

In HN33, an immortalized hippocampal neuronal cell line, VEGF reduced cell death associated with an in vitro model of cerebral ischemia: at a maximally effective concentration of 50 ng/ml, V EGF approximately doubled the number of cells surviving after 24 h of hypoxia and glucose deprivation.

VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia.

In the ischemic brain VEGF exerts an acute neuroprotective effect, as well as longer latency effects on survival of new neurons and on angiogenesis, and that these effects appear to operate independently.

Vascular endothelial growth factor rescues hippocampal neurons from glutamate‐induced toxicity: signal transduction cascades

  • H. MatsuzakiM. Tamatani M. Tohyama
  • Biology, Chemistry
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2001
It is suggested that VEGF has a protective effect on hippocampal neurons against glutamate‐induced toxicity and that this effect is dependent on PI3‐ K/Akt and MEK/ERK signaling pathways mediated primarily through Flk‐1 receptor.

Cell type specific upregulation of vascular endothelial growth factor in an MCA-occlusion model of cerebral infarct.

The spatial and temporal correlation between the induction of angiogenesis with V EGF and VEGFR-1 expression suggests that the ischemic upregulation of VEGF represents a physiological response of the brain to counterbalance hypoxia/ischemia in order to protect neuroectodermal tissue.