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 8h 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 mm3 n=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.
Zweckberger
Klaus
K
Institute for Surgical Research, Department of Neurosurgery, University of Munich Medical Center-Grosshadern, Munich, Germany. klaus.zweckberger@med.uni-heidelberg.de
Plesnila
Nikolaus
N
D000818:Animals; D065094:Bradykinin B2 Receptor Antagonists; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology; D007279:Injections, Subcutaneous; D019586:Intracranial Hypertension / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use*
D065094:Bradykinin B2 Receptor Antagonists; C403051:LF 16-0687; D018696:Neuroprotective Agents; D011804:Quinolines