Aktuelle Neurologie 2005; 32 - P663
DOI: 10.1055/s-2005-919693

Microplasmin reduces microvascular damage and blood brain barrier disruption following experimental stroke

M.R Vosko 1, M Schubert 1, A Trinkl 1, J.M Stassen 1, M Dichgans 1, G.F Hamann 1
  • 1Munich; Leuven, B; Wiesbaden

Microvascular basal lamina integrity plays an essential role in blood-brain barrier disturbances following ischemic stroke. About 9% of stroke patient treated with rt-PA experience a thrombolysis-related secondary intracerebral hemorrhage.

There is a need to find alternative thrombolytic substances with reduced adverse effects. We examined the influence of microplasmin (recombinantly generated truncated plasmin with thrombolytic action) on microvascular damage, blood brain barrier disruption and amount of endogenous tPA and uPA after focal ischemia and reperfusion in the rat.

Male whistar rats were subjected to focal cerebral ischemia (I, 3h) and reperfusion (R, 24h) using the intraluminal thread model. Rats received either treatment (microplasmin 10mg/kg body weight, n=6) or saline (control group, n=7) at the end of ischemia period. Collagen type IV, a major component of the microvascular basal lamina, was determined in brain tissue by means of immunohistochemistry. TPA and uPA were measured by plasminogen zymography. We found a significant reduction of basal lamina damage in the ischemic basal ganglia of the microplasmin treated group in comparison to controls: collagen type IV stained area 85%±5% vs. 75%±4%, (Mean±SEM). The number of collagen stained vessels remained without a significant difference (83%±3% vs. 83%±4%, respectively). TPA activity did not differ between groups (111%±13% vs. 104%±15%) whereas uPA activity increased in both groups, but was significantly lower (635%±20%) in the microplasmin group than in controls (1019%±22%). There was a trend towards reduced extravasation of hemoglobin (442%±28% vs. 380%±25%, resp., n.s.)

Microplasmin showed a protective effect on the microvascular basal lamina and the blood brain barrier. The reduced uPA elevation could be responsible for this protective effect after microplasmin administration.

Parts of the present work were presented at the International Stroke Conference in New Orleans on February 2–5, 2005.