Experimental Study Of The Time-Phase On The Variation Of Blood-Brain Barrier Permeability And MMPs Expression After Cerebral Ischemia Reperfusion In Rats

Objective To investigate the variation of blood-brain barrier (BBB ) permeability and matrix metalloproteinase-2 (MMP-2) expression of the injured side of brain at different time points of reperfusion after focal cerebral ischemical, in order to research the mechanisms of BBB injury further and provid the experiment evidence for the treatment ofischemic cerebrovascular disease (ICVD) .Methods In this paper, the models of focal cerebral ischemia reperfusion in rats were established with suture-occluded method. The BBB permeability was assessed by evans blue (EB) content of brain tissue, and the water content of brain reflected the degree of brain edema. We observated MMP-2 expression of brain with immunohistochemical method and determined superoxide dismutase (SOD) activity and malondialdehyde (MDA) content of the blood serum.Results1. The EB content of brain obviously increased in the injured side compared with normal control group after middle cerebral artery occlusion (MCAO) reperfusion 3h, subsequently it continued increasing and reached the first crest on reperfusion 24h. The EB content of brain decreased on reperfusion 48h compared with reperfusion 24h, and it increased again on reperfusion 72h. The EB content of brain recovered after reperfusion 5 day.2. The water content of brain obviously increased in the injured side compared withnormal control group after MCAO reperfusion 3h, subsequently it increased further and reached the two peaks on reperfusion 24h and 72h. The water content of brain recovered after reperfusion 5 day.3. The interstitial edema appeared in histomorphology examination after MCAO reperfusion 3h, and the time of two most marked tissue edema were on reperfusion 24h and 72h, the same time-phase as the variation of the water content of brain. And the interstitial edema recovered after reperfusion 5 day.4. MMP-2 expression of the injured side of brain was in vascular endothelial cell(VEC), nerve cells and glial cells after MCAO reperfusion 3h, and there was still MMP-2 expression in a little glial cells after reperfusion 5 day. There was no MMP-2 expression in VEC and nerve cells of the injured side after refusion 5d and in the uninjured side of brain.5. SOD activity decreased and MDA content increased in the blood serum compared with normal control group after MCAO reperfusion 3h, and reached the crest on reperfusion 24h. The two recovered after reperfusion 5 day.6. The variation of EBcontent and water content of brain were in the same time-phase after MCAO reperfusion 3h, and the peak times of the two were on reperfusion 24h and 72h. The changes of SOD activity and MDA content in the blood serum were coherent of time, and the peak time of the two was on reperfusion 24h as the first peak time of the increasing of EB content. Marked changes of the four happened on reperfusion 3h and recovered obviously after reperfusion 5day.Conclusions1. The structure and function of BBB were already damaged on reperfusion 3h in the injured side of brain, and BBB permeability was heightened. The BBB permeability recovered after reperfusion 5 day.2. The BBB permeability varied along with reperfusion after focal cerebral...