Blood-brain barrier dysfunction in ischemic stroke: targeting tight junctions and transporters for vascular protection.

TitleBlood-brain barrier dysfunction in ischemic stroke: targeting tight junctions and transporters for vascular protection.
Publication TypeJournal Article
Year of Publication2018
AuthorsAbdullahi W, Tripathi D, Ronaldson PT
JournalAm J Physiol Cell Physiol
Date Published2018 Sep 01
KeywordsAnimals, Biological Transport, Blood-Brain Barrier, Brain Ischemia, Endothelial Cells, Humans, Membrane Transport Proteins, Stroke, Tight Junction Proteins, Tight Junctions

The blood-brain barrier (BBB) is a physical and biochemical barrier that precisely controls cerebral homeostasis. It also plays a central role in the regulation of blood-to-brain flux of endogenous and exogenous xenobiotics and associated metabolites. This is accomplished by molecular characteristics of brain microvessel endothelial cells such as tight junction protein complexes and functional expression of influx and efflux transporters. One of the pathophysiological features of ischemic stroke is disruption of the BBB, which significantly contributes to development of brain injury and subsequent neurological impairment. Biochemical characteristics of BBB damage include decreased expression and altered organization of tight junction constituent proteins as well as modulation of functional expression of endogenous BBB transporters. Therefore, there is a critical need for development of novel therapeutic strategies that can protect against BBB dysfunction (i.e., vascular protection) in the setting of ischemic stroke. Such strategies include targeting tight junctions to ensure that they maintain their correct structure or targeting transporters to control flux of physiological substrates for protection of endothelial homeostasis. In this review, we will describe the pathophysiological mechanisms in cerebral microvascular endothelial cells that lead to BBB dysfunction following onset of stroke. Additionally, we will utilize this state-of-the-art knowledge to provide insights on novel pharmacological strategies that can be developed to confer BBB protection in the setting of ischemic stroke.

Alternate JournalAm J Physiol Cell Physiol
PubMed ID29949404
PubMed Central IDPMC6171039
Grant ListR01 NS084941 / NS / NINDS NIH HHS / United States
Faculty Member Reference: 
Patrick T Ronaldson, PhD, FAAPS