Bradykinin B-2, but not B-1, receptor antagonism has a neuroprotective effect after brain injury

The aim of the present study was to measure the therapeutic effects of brad ykinin antagonists on lesion volume and brain swelling induced by cold inju ry in the parietal cortex of rat and mouse, respectively. Cold lesion was i nduced by application of a precooled (-78 degreesC) copper cylinder (3 min diameter) to the intact dura of rat and mouse for 6 and 30 see, respectivel y. At 24 h after the injury, the brains were removed and lesion volume was determined by the triphenyltetrazolium chloride method in rats. In the mous e, brain swelling was expressed as percentage increase in weight of the inj ured hemisphere which is compared to the contralateral side. After a subcut aneous priming dose of 18 mug/kg, a 1-h pretreatment and 24-h posttreatment using osmotic minipumps (300 ng/kg (.) min) was applied. Hoe140, a bradyki nin 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 mo use. In contrast, the bradykinin receptor 1 antagonist, B 9858, had no effe ct 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 m ediated by bradykinin and can be successfully treated with B-2 antagonists.