Early activation of matrix metalloproteinase-9 is associated with blood-brain barrier disruption after photothrombotic cerebral ischemia in rats.
BACKGROUND
The activation of matrix metalloproteinases (MMPs) is a critical event for disruption of the blood-brain barrier (BBB) during cerebral ischemia. Among the MMPs, MMP-2, and MMP-9 expression were reported to be significantly elevated after the onset of ischemia. The aim of this study was to investigate which one is more significant for BBB disruption in the photothrombotic cerebral ischemia.


METHODS
Male Sprague-Dawley rats weighing 250-300 g received focal cerebral ischemia by photothrombosis. MMP-2 and MMP-9 activities were assessed by gelatin zymography at various times from 2 h to 7 days. The BBB integrity was assessed using Evans blue dye with a spectrophotometric assay.


RESULTS
The Evans blue extravasation was increased within 2 h after cerebral ischemia, and was maximal at 12 and 24 h after the injury, and then gradually decreased. MMP-9 protein activity was detected as early as 2 h after the focal ischemic event; it rapidly increased at 6 h after ischemia, and reached a maximum level 48 h after the ischemic event. Thereafter, the MMP-9 level abruptly decreased and returned to the baseline at 72 h after the insult. By contrast, the MMP-2 protein activity was up-regulated at 6 h after the focal ischemic insult, and reached a maximum level at 72 h after the event. The elevated MMP-2 levels persisted for 7 days after the injury.


CONCLUSIONS
The early activation of MMP-9 was correlated with the increase in the permeability of the BBB. Our findings suggest that MMP-9 is the key factor involved in BBB disruption and subsequent brain injury after photothrombotic cerebral ischemia in rats.
Piao
Min-Sheng
MS
Department of Neurosurgery, Chonnam National University Medical School, Gwangju, Republic of Korea.
Lee
Jung-Kil
JK
Park
Chun-Soon
CS
Ryu
Han-Seung
HS
Kim
Soo-Han
SH
Kim
Hyung-Seok
HS
D000818:Animals; D001812:Blood-Brain Barrier / Q000201:enzymology* / Q000503:physiopathology*; D002545:Brain Ischemia / Q000201:enzymology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000502:physiology; D020767:Intracranial Thrombosis / Q000209:etiology / Q000503:physiopathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D010775:Photic Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley
D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9