Anatibant,a selective non-peptide bradykinin B2 receptor antagonist,reduces intracranial hypertension and histopathological damage after experimental traumatic brain injury

Bradykinin, the main metabolite of the kallikrein-kinin system and one of the first mediators released during inflammation, is well known to increase the permeability of the blood brain barrier (BBB) by activation of kinin B₂ receptors and hence promote brain edema formation following traumatic brain injury (TBI). Anatibant^® (LF 16-0687), a selective non-peptide bradykinin B₂ receptor antagonist, reduces brain edema after experimental TBI, however, so far no data are available if Anatibant^® reduces also the sequels of brain edema formation, i.e. morphological brain damage. Therefore, we investigated the effect of Anatibant (3.0 mg/kg b.w.) on intracranial pressure (ICP) and contusion volume after experimental TBI. Male C57/Bl6 mice (25–28 g) were subjected to Controlled Cortical Impact trauma (CCI). Anatibant^® was administrated as a subcutaneous bolus 15 min and 8 h after TBI. ICP was measured 3, 6, and 10 h after injury and contusion volume was quantified 24 h after trauma. Our data demonstrate a significant reduction of ICP (16.6 ± 1.67 mmHg vs. 24.40 ± 3.58 mmHg; n = 6; p = 0.002) and of contusion volume 24 h after trauma (28.28 ± 5.18 mm³ vs. 35.0 ± 3.32 mm³n = 7; p = 0.003) in treated mice. Therefore we conclude, that inhibition of bradykinin B₂ receptors seems to be a promising treatment option, and might therefore be investigated in clinical trails for the treatment of TBI.