VEGF Signaling in Neurological Disorders.

Joon Shim,Joseph Madsen

doi:10.3390/ijms19010275

Abstract

Vascular endothelial growth factor (VEGF) is a potent growth factor playing diverse roles in vasculogenesis and angiogenesis. In the brain, VEGF mediates angiogenesis, neural migration and neuroprotection. As a permeability factor, excessive VEGF disrupts intracellular barriers, increases leakage of the choroid plexus endothelia, evokes edema, and activates the inflammatory pathway. Recently, we discovered that a heparin binding epidermal growth factor like growth factor (HB-EGF)—a class of EGF receptor (EGFR) family ligands—contributes to the development of hydrocephalus with subarachnoid hemorrhage through activation of VEGF signaling. The objective of this review is to entail a recent update on causes of death due to neurological disorders involving cerebrovascular and age-related neurological conditions and to understand the mechanism by which angiogenesis-dependent pathological events can be treated with VEGF antagonisms. The Global Burden of Disease study indicates that cancer and cardiovascular disease including ischemic and hemorrhagic stroke are two leading causes of death worldwide. The literature suggests that VEGF signaling in ischemic brains highlights the importance of concentration, timing, and alternate route of modulating VEGF signaling pathway. Molecular targets distinguishing two distinct pathways of VEGF signaling may provide novel therapies for the treatment of neurological disorders and for maintaining lower mortality due to these conditions.

Highlights

Vascular endothelial growth factor (VEGF) is a potent growth factor playing diverse roles in vasculogenesis and angiogenesis
The goal of this review is to provide a brief overview of VEGF signaling in cerebrovascular disease such as stroke with subarachnoid hemorrhage (SAH), post-stroke hydrocephalus and age-related neurological disorders
Because the leading cause of mortality in the world and in the USA besides cancer is cardiovascular disease, we review status of VEGF and ErbB/EGF receptor (EGFR) inhibition therapy used in non-neoplastic conditions through a well-established cardiovascular risk factor and consider how the relevant approaches can be translated to the particular neuropathological conditions

Summary

Introduction

Vascular endothelial growth factor (VEGF) is a potent growth factor playing diverse roles in vasculogenesis and angiogenesis. One of the fascinating aspects of VEGF among others would be its regulatory role for growth of blood vessels in accordance with outgrowth of nervous network in an orientation opposite to the neural migration in the developing brain. This crosstalk between neurons and vascular niche (microenvironment) is shown to continue after birth and low levels of VEGF contributes to the trophic function or neuroprotection in the central nervous system [3,4]. Its cost effectiveness has been argued [5], VEGF inhibition therapy using bevacizumab or a similar class of angiogenesis inhibitors is considered an acceptable approach in cancer. Inhibiting downstream pathway of VEGF signaling through angiogenesis inhibitor and/or glucocorticoids has shown a protective effect against germinal matrix hemorrhage [8,9]

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