The Temporal Changes of Matrix Metalloproteinases in Experimental Middle Cerebral Artery Occlusion and Reperfusion

Lee, Kyung Yul; Yang, Won Seok; Kim, Eun Hee; Heo, Ji Hoe; Kim, Dong Goo

Abstract

BACKGROUND: Matrix metalloproteinases (MMPs) can degrade a wide range of extracellular matrix components. The degradation of microvascular basal lamina by MMPs may be, in part, responsible for the hemorrhagic transformation, brain edema, and accentuation of ischemic injury in cerebral ischemia. Although MMP-2 and MMP-9 were reported to increase in cerebral ischemia, the temporal patterns of their increase are uncertain.
METHODS
By using gelatin zymography, we investigated the activity of MMP-2 and MMP-9 in 10 micrometer frozen sections of ischemic and non-ischemic hemispheres in spontaneous hypertensive rats (SHRs) after variable time of reperfusion following 2 hours of middle cerebral artery occlusion (MCA:O). Adjacent 2mm-thick slices were stained with 2,3,5-triphenyltetrazolium chloride (TTC) solution to define the area of ischemic damage.
RESULTS
The infarcted zone could be visualized well by TTC staining after 3 hours of reperfusion. MMP-2 was observed in all samples examined, while MMP-9 was observed only in the ischemic hemispheres. In the ischemic hemispheres when comparing with non-ischemic sides, MMP-9 was increased in all groups undergoing MCA:O, as early as in 2 hours of MCA:O group, while MMP-2 was increased only after 6 days in the reperfusion group. MMP-2 and MMP-9 activities per unit volume of infarction increased during the reperfusion period and were highest after 6 days.
CONCLUSIONS
MMP-9 increased early after MCA:O in the SHR and both MMP-2 and MMP-9 increased during the reperfusion period. These findings highlight the early potential role of MMP-9 in cerebral ischemia. (J Korean Neurol Assoc 19(3):278~284, 2001)