Recombinant tissue plasminogen activator attenuates basal lamina antigen loss after experimental focal cerebral ischemia

Background and purpose: The use of recombinant tissue plasminogen activator (rt-PA) is a proven therapy in acute stroke. Main concerns are based on hemorrhagic complications, which are connected with microvascular integrity loss. The aim of this study was to evaluate microvascular changes after various doses of rt-PA. Methods and results: Focal cerebral ischemia for 3 hours was induced using the suture model in rats and followed by 24 hours of reperfusion. Six rats received either saline, 0.9, 9, or 18 mg rt-PA/kg body weight at the end of ischemia. By immunostaining of colla en type IV the, density of microvessels and the total stained area in the basal ganglia an cortex was measured. Comparison of the ischemic with the non-ischemic hemisphere showed significantly less reduction of the number of microvessels in rats treated with low-dose rt-PA than in the other groups: controls 17 +/- 3% (basal ganglia), 12 +/- 7% (cortex); 0.9 mg rt-PA, 18 +/- 3%, 10 +/- 4%; 9 mg, 21 +/- 4%, 13 +/- 7%; 18 mg, 22 +/- 4%, 15 +/- 8%. A similar effect was observed on the total stained area: control 25 +/- 4% (basal ganglia), 14 +/- 7% (cortex); 0. 9 mg rt-PA, 23 +/- 2%, 7 +/- 4%; 9 mg, 28 +/- 4%, 15 +/- 4%; 18 mg, 29 +/- 4%, 17 +/- 5%, p < 0.001. The significant reduction of the area of infarction after low and moderate doses-of rt-PA was visualized with an MAP2-antibody, and the volume was calculated by 3-D reconstruction: control, 165.2 mm 3 +/- 21 %; 0. 9 mg rt-PA, 102.6 mm 3 +/- 16%; 9 mg, 101.2 mm 3 +/- 17%; 18 mg, 133.0 mm 3 +/- 24%; p < 0.001. Conclusions: Rats exposed to low-dose rt-PA preserved basal lamina structures, and showed smaller infarct sizes. The protective effect of low-dose rt-PA might be due to an increased microvascular patency rate.