Brain endothelial cell specific integrins and ischemic stroke

Abstract

Ischemic stroke, a devastating event caused by the blockage of a blood vessel(s) supplying the brain, continues to affect thousands of people in the USA every year. While no true advances in stroke therapy have arisen to further improve patient outcomes since the introduction of the blood clot buster tissue plasminogen activator and mechanical clot removal, fewer people are dying from the immediate stroke insult. Instead, patients often suffer significant morbidity due to post-recanalization secondary damage. Central to this damage is the breakdown of the blood–brain barrier, which, in addition to contributing to edema and inflammation, triggers an upregulation in angiogenic growth factors in the brain’s attempt to salvage and repair itself. Recent studies have begun to improve our understanding of the post-stroke angiogenic response of brain endothelial cells in the ischemic penumbra, which has long been held to be an important site for medical intervention. These studies suggest that endothelial cell integrin matrix receptors play an important and therapeutically significant role in moderating cellular responses to ischemic brain injury.

Keywords::

• blood–brain barrier
• endothelial
• extracellular matrix
• integrins
• stroke

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Stroke is a leading cause of death and significant morbidity worldwide.

• Therapeutic options for stroke patients are limited to tissue plasminogen activator administration and intra-arterial thrombectomy.

• Both of these current treatment options carry heavy risk and are often highly exclusive.

• Brain endothelial cell integrins are transmembrane dimeric proteins, which are involved in cell adhesion as well as signal transduction.

• Certain integrins are up-/downregulated rapidly after stroke onset, while others are expressed chronically.

• α₅β₁ integrin could stabilize the blood–brain barrier after the onset of cerebral ischemia.

• Integrins represent an attractive therapeutic target for modulating post-stroke recovery.

Notes