Aging, the metabolic syndrome, and ischemic stroke: redefining the approach for studying the blood-brain barrier in a complex neurological disease

Adv Pharmacol. 2014:71:411-49. doi: 10.1016/bs.apha.2014.07.001. Epub 2014 Sep 12.


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.

Keywords: Comorbidity; Diabetes; Hypertension; Middle cerebral artery occlusion; Neurovascular unit.

Publication types

  • Review

MeSH terms

  • Aging / physiology*
  • Animals
  • Brain / cytology*
  • Brain / metabolism
  • Cellular Senescence
  • Humans
  • Metabolic Syndrome* / epidemiology
  • Metabolic Syndrome* / metabolism
  • Stroke* / epidemiology
  • Stroke* / metabolism