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Author Notes:
Correspondence: Manuel Yepes, Department of Neurology and Center for Neurodegenerative Disease, Emory University, Whitehead Biomedical Research Building, 615 Michael Street, Suite 505J, Atlanta, GA 30322, USA e-mail: myepes@emory.edu
Disclosures: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Subjects:
Research Funding:
This work was supported in part by National Institutes of Health Grant NS-079331 (to Manuel Yepes) and NS-062073 (to Manuel Yepes), and VA MERIT award BX000474 (to Manuel Yepes).
Keywords:
- cerebral ischemia
- neurovascular unit
- blood-brain barrier
- middle cerebral artery occlusion
- tumor necrosis factor-like weak inducer of apoptosis
- fibroblast growth factor-inducible 14
- cerebral edema
- nuclear factor kappa-light-chain-enhancer of activated B cells
TWEAK and Fn14 in the Neurovascular Unit
Abstract:
The neurovascular unit (NVU) is a dynamic structure assembled by endothelial cells (EC), a basement membrane (BM), perivascular astrocytes (PA), pericytes, and surrounding neurons. The NVU regulates the passage of substances and cellular elements from the intravascular space into the brain parenchyma. This function, also known as blood-brain barrier (BBB), is regulated by the integrity of tight junctions proteins between EC, and the interaction between PA and the basal lamina. The cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) are abundantly expressed in the NVU. Here we will review data indicating that the interaction between TWEAK and Fn14 in the endothelial cell-BM-astrocyte interface regulates the function of the BBB following an ischemic/hypoxic injury, and that pharmacological inhibition of TWEAK-Fn14 is a promising target for the treatment of patients with neurological diseases that have a direct impact on the structure and function of the NVU.
Keywords: cerebral ischemia, neurovascular unit, blood-brain barrier, middle cerebral artery occlusion, tumor necrosis factor-like weak inducer of apoptosis, fibroblast growth factor-inducible 14, cerebral edema, nuclear factor kappa-light-chain-enhancer of activated B cells
Copyright information:
© 2013 Yepes
This is an Open Access work distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/).
