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VEGF: A potential target for hydrocephalus

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Abstract

Growth factors are primarily responsible for the genesis, differentiation and proliferation of cells and maintenance of tissues. Given the central role of growth factors in signaling between cells in health and in disease, it is understandable that disruption of growth factor-mediated molecular signaling can cause diverse phenotypic consequences including cancer and neurological conditions. This review will focus on the specific questions of enlarged cerebral ventricles and hydrocephalus. It is also well known that angiogenic factors, such as vascular endothelial growth factor (VEGF), affect tissue permeability through activation of receptors and adhesion molecules; hence, recent studies showing elevations of this factor in pediatric hydrocephalus led to the demonstration that VEGF can induce ventriculomegaly and altered ependyma when infused in animals. In this review, we discuss recent findings implicating the involvement of biochemical and biophysical factors that can induce a VEGF-mimicking effect in communicating hydrocephalus and pay particular attention to the role of the VEGF system as a potential pharmacological target in the treatment of some cases of hydrocephalus. The source of VEGF secretion in the cerebral ventricles, in periventricular regions and during pathologic events including hydrocephalus following hypoxia and hemorrhage is sought. The review is concluded with a summary of potential non-surgical treatments in preclinical studies suggesting several molecular targets including VEGF for hydrocephalus and related neurological disorders.

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Abbreviations

AD:

Alzheimer’s disease

AQP-4:

Aquaporin-4

BBB:

Blood–brain barrier

CP:

Choroid plexus

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

E-, N-, P-cadherin:

Epithelial, neuronal, placental cadherin

GPCRs:

G protein-coupled receptors

Hyh:

Hy5-homolog, DNA binding/transcription factor

NPH:

Normal pressure hydrocephalus

VE-cadherin:

Vascular endothelial cadherin

VEGF:

Vascular endothelial growth factor

VEGFR2:

Vascular endothelial growth factor receptor 2

ZO-1:

Zonula occludin 1

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Acknowledgments

We thank Dr. Michael Klagsbrun and members of the Neurodynamics laboratory at Boston Children’s Hospital and Harvard Medical School for their comment and support. We appreciate comments by Dr. Roger D. Kamm at the Massachusetts Institute of Technology and support by Dr. Bonnie Blazer-Yost and Dr. Hiroki Yokota at the Indiana University Purdue University Indianapolis. We also thank Dr. Jenna Koschnitzky at The Hydrocephalus Association (HA) for critical reading of this manuscript. J.W.S. is a recipient of the HA mentored young investigator award. We also thank the Swedish Brain Foundation and Umeå University Hospital for their support to J.S. Numerous leading laboratories have contributed to the advancement of hydrocephalus research to understand the pathophysiology in pursuit of potential treatments. We apologize to those researchers whose work we are not citing here because of space limitation.

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Authors and Affiliations

  1. Department of Biology, Indiana University-Purdue University Indianapolis, 723 W. Michigan Street SL354, Indianapolis, IN, 46202, USA

    Joon W. Shim

  2. Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive L235, Stanford, CA, 94305, USA

    Johanna Sandlund

  3. Clinical Microbiology Laboratory, Stanford University Medical Center, 3375 Hillview Avenue Palo, Alto, CA, 94304, USA

    Johanna Sandlund

  4. Department of Neurosurgery, Department of Surgery, Boston Children’s Hospital and Harvard Medical School, 300 Longwood Ave, Boston, MA, 02115, USA

    Joseph R. Madsen

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  1. Joon W. Shim
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Correspondence to Joseph R. Madsen.

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Shim, J.W., Sandlund, J. & Madsen, J.R. VEGF: A potential target for hydrocephalus. Cell Tissue Res 358, 667–683 (2014). https://doi.org/10.1007/s00441-014-1978-6

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