Plasminogen activation in experimental permanent focal cerebral ischemia

Background: Previous experimental work using in situ zymography has shown v ery early increased plasminogen activation in ischemic regions after 3 h of ischemia with and without reperfusion. The objective of the present study was to evaluate the time course and extent of plasminogen activation in lon g-term permanent focal cerebral ischemia. Material and methods: The middle cerebral artery in male Fisher rats was irreversibly occluded by electrocoa gulation. Duration of ischemia was 48, 72, and 168 h. Occlusion was control led in vivo by MRI at day 2. Plasminogen activation was detected by in situ zymography of 10 mum cryosections with an overlay containing plasminogen a nd the plasmin substrate caseine. Areas of plasminogen activation were comp ared to structural lesions (immunohistochemical loss of microtubule-associa ted protein 2; MAP 2). Results: Compared to controls, increased plasminogen activation was observed in the basal ganglia and the cortex of the ischemi c hemisphere after 48, 72, and 168 h (affected area of basal ganglia: 44.5/-21.9, 70.1+/-2.3 and 66.6+/-2.8%, respectively; affected area of cortex: 63.4+/-9.8, 67.7+/-0.7 and 64.0+/-3.7%, respectively). The duration of isch emia had no significant influence on the extent of plasminogen activation. Areas of increased plasminogen activation significantly overlapped with and exceeded areas of MAP 2 loss (P<0.005). Discussion: Permanent focal cerebr al ischemia leads to increased plasminogen activation in ischemic regions. This plasminogen activation remains elevated at persistent levels over days . It may contribute to extracellular matrix (ECM) disruption, secondary hem orrhage, and brain edema in subacute stages of ischemic stroke. (C) 2000 El sevier Science BN. All rights reserved.