Bradykinin B2, but not B1, receptor antagonism has a neuroprotective effect after brain injury.

Abstract

The aim of the present study was to measure the therapeutic effects of bradykinin antagonists on lesion volume and brain swelling induced by cold injury in the parietal cortex of rat and mouse, respectively. Cold lesion was induced by application of a precooled (-78 degrees C) copper cylinder (3 mm diameter) to the intact dura of rat and mouse for 6 and 30 sec, respectively. At 24 h after the injury, the brains were removed and lesion volume was determined by the triphenyltetrazolium chloride method in rats. In the mouse, brain swelling was expressed as percentage increase in weight of the injured hemisphere which is compared to the contralateral side. After a subcutaneous priming dose of 18 microg/kg, a 1-h pretreatment and 24-h posttreatment using osmotic minipumps (300 ng/kg x min) was applied. Hoe140, a bradykinin receptor 2 antagonist, revealed a 19% reduction of lesion volume (p < 0.05) in the rat and a 14% diminution of brain swelling (p < 0.05) in the mouse. In contrast, the bradykinin receptor 1 antagonist, B 9858, had no effect on lesion volume compared to sham treated rats. When B 9858 was given in combination with Hoe140, a significant reduction in lesion volume was seen which was equivalent to and not different from that seen with Hoe140 alone in the rat. We conclude that brain injury after cold lesion is partially mediated by bradykinin and can be successfully treated with B2 antagonists.