Vasogenic edema due to tight junction disruption by matrix metalloproteinases in cerebral ischemia

Gary A Rosenberg, Yi Yang
Neurosurgical Focus 2007 May 15, 22 (5): E4
Cerebral ischemia causes cell swelling and breakdown of the blood-brain barrier (BBB). Cytotoxic edema results from energy failure, and vasogenic edema occurs when the blood vessels are damaged. Proteases and free radicals are the end result of a molecular injury cascade. Matrix metalloproteinases (MMPs) are a gene family of extracellular matrix-degrading enzymes that disrupt the BBB. Tight junction proteins (TJPs), occludin and claudin-5, which form the endothelial barrier, are vulnerable to attack by MMPs. Basal lamina proteins, such as fibronectin, laminin, and heparan sulfate, are also degraded by MMPs. Reperfusion injury leads to a biphasic opening of the BBB, with the early opening occurring several hours after the onset of reperfusion due to activation of the constitutive enzyme gelatinase A (MMP-2). This initial opening is transient and followed 24 to 48 hours later by more intense damage to the blood vessel, which is associated with the expression and activation of gelatinase B (MMP-9) and stromelysin-1 (MMP-3). Synthetic MMP inhibitors restore the early integrity of the BBB but are ineffective in the later opening. Because these inhibitors block MMPs involved in angiogenesis and neurogenesis, they also slow recovery. The challenge is to identify agents that will protect the BBB, blocking vasogenic edema without interfering with recovery.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"