Peripheral thermal injury causes blood-brain barrier dysfunction and matrix metalloproteinase (MMP) expression in rat.
Mortality after serious systemic thermal injury may be linked to significant increases in cerebral vascular permeability and edema due to blood-brain barrier (BBB) breakdown. This BBB disruption is thought to be mediated by a family of proteolytic enzymes known as matrix metalloproteinases (MMPs). The gelatinases, MMP-2 and MMP-9, digest the endothelial basal lamina of the BBB, which is essential for maintaining BBB integrity. The current study investigated whether disruption of microvascular integrity in a rat thermal injury model is associated with gelatinase expression and activity. Seventy-two adult Sprague-Dawley rats were anesthetized and submerged horizontally, in the supine position, in 100 degrees C (37 degrees C for controls) water for 6 s producing a third-degree burn affecting 60-70% of the total body surface area. Brain edema was detected by calculating water content. Real time PCR, Western blot, and zymography were used to quantify MMP mRNA, protein, and enzyme activity levels. Each group was quantified at 3, 7, 24, and 72 h post thermal injury. Brain water content was significantly increased 7 through 72 h after burn. Expression of brain MMP-9 mRNA was significantly increased as early as 3 h after thermal injury compared to controls, remained at 7 h (p<0.01), and returned to control levels by 24 h. MMP-9 protein levels and enzyme activity began to increase at 7 h and reached significant levels between 7 and 24 h after thermal injury. While MMP-9 protein levels continued to increase significantly through 72 h, enzyme activity returned to control level. The increase in MMP-9 expression and activity, associated with increased BBB permeability following thermal injury, indicates that MMP-9 may contribute to observed cerebral edema in peripheral thermal injury.
Swann
Kathryn
K
Plastic and Reconstructive Surgery, USA.
Berger
Jamie
J
Sprague
Shane M
SM
Wu
Yimin
Y
Lai
Qin
Q
Jimenez
David F
DF
Barone
Constance M
CM
Ding
Yuchuan
Y
D000818:Animals; D001485:Basement Membrane / Q000201:enzymology / Q000648:ultrastructure; D001812:Blood-Brain Barrier / Q000201:enzymology / Q000503:physiopathology*; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D001929:Brain Edema / Q000201:enzymology / Q000209:etiology* / Q000503:physiopathology*; D002056:Burns / Q000150:complications* / Q000503:physiopathology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000201:enzymology / Q000648:ultrastructure; D004789:Enzyme Activation / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000502:physiology
D012333:RNA, Messenger; D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9