title: Aging, the metabolic syndrome, and ischemic stroke: redefining the approach for studying the blood-brain barrier in a complex neurological disease.
abstract: The blood-brain barrier (BBB) has many important functions in maintaining the brain's immune-privileged status. Endothelial cells, astrocytes, and pericytes have important roles in preserving vasculature integrity. As we age, cell senescence can contribute to BBB compromise. The compromised BBB allows an influx of inflammatory cytokines to enter the brain. These cytokines lead to neuronal and glial damage. Ultimately, the functional changes within the brain can cause age-related disease. One of the most prominent age-related diseases is ischemic stroke. Stroke is the largest cause of disability and is third largest cause of mortality in the United States. The biggest risk factors for stroke, besides age, are results of the metabolic syndrome. The metabolic syndrome, if unchecked, quickly advances to outcomes that include diabetes, hypertension, cardiovascular disease, and obesity. The contribution from these comorbidities to BBB compromise is great. Some of the common molecular pathways activated include: endoplasmic reticulum stress, reactive oxygen species formation, and glutamate excitotoxicity. In this chapter, we examine how age-related changes to cells within the central nervous system interact with comorbidities. We then look at how comorbidities lead to increased risk for stroke through BBB disruption. Finally, we discuss key molecular pathways of interest with a focus on therapeutic targets that warrant further investigation.
authors.affiliation: Department of Neurosurgery, West Virginia University, School of Medicine, Morgantown, West Virginia, USA; The Center for Neuroscience, West Virginia University, School of Medicine, Morgantown, West Virginia, USA.
authors.forename: Brandon P
authors.initials: BP
authors.lastname: Lucke-Wold
authors.affiliation: The Center for Neuroscience, West Virginia University, School of Medicine, Morgantown, West Virginia, USA; Department of Basic Pharmaceutical Sciences, West Virginia University, School of Pharmacy, Morgantown, West Virginia, USA.
authors.forename: Aric F
authors.initials: AF
authors.lastname: Logsdon
authors.affiliation: Department of Neurosurgery, West Virginia University, School of Medicine, Morgantown, West Virginia, USA; The Center for Neuroscience, West Virginia University, School of Medicine, Morgantown, West Virginia, USA.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Turner
authors.affiliation: Department of Neurosurgery, West Virginia University, School of Medicine, Morgantown, West Virginia, USA; The Center for Neuroscience, West Virginia University, School of Medicine, Morgantown, West Virginia, USA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Rosen
authors.affiliation: The Center for Neuroscience, West Virginia University, School of Medicine, Morgantown, West Virginia, USA; Department of Basic Pharmaceutical Sciences, West Virginia University, School of Pharmacy, Morgantown, West Virginia, USA. Electronic address: jhuber@hsc.wvu.edu.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Huber
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D016922:Cellular Senescence; D006801:Humans; D024821:Metabolic Syndrome / Q000453:epidemiology / Q000378:metabolism; D020521:Stroke / Q000453:epidemiology / Q000378:metabolism
keywords: Comorbidity; Diabetes; Hypertension; Middle cerebral artery occlusion; Neurovascular unit