Plasminogen activation in experimental permanent focal cerebral ischemia.
BACKGROUND
Previous experimental work using in situ zymography has shown very 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 long-term permanent focal cerebral ischemia.


METHODS
The middle cerebral artery in male Fisher rats was irreversibly occluded by electrocoagulation. Duration of ischemia was 48, 72, and 168 h. Occlusion was controlled in vivo by MRI at day 2. Plasminogen activation was detected by in situ zymography of 10 microm cryosections with an overlay containing plasminogen and the plasmin substrate caseine. Areas of plasminogen activation were compared to structural lesions (immunohistochemical loss of microtubule-associated protein 2; MAP 2).


RESULTS
Compared to controls, increased plasminogen activation was observed in the basal ganglia and the cortex of the ischemic 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 ischemia 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).


CONCLUSIONS
Permanent focal cerebral 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 hemorrhage, and brain edema in subacute stages of ischemic stroke.
Pfefferkorn
T
T
Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-Universität München, Marchioninistr. 15, 81377, Munich, Germany.
Wiessner
C
C
Allegrini
P R
PR
Staufer
B
B
Vosko
M R
MR
Liebetrau
M
M
Bueltemeier
G
G
Kloss
C U
CU
Hamann
G F
GF
D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D008869:Microtubule-Associated Proteins; D010958:Plasminogen