Detrimental role of bradykinin B2 receptor in a murine model of diffuse brain injury

被引:55
|
作者
Hellal, F
Pruneau, D
Palmier, B
Faye, P
Croci, N
Plotkine, M
Marchand-Verrecchia, C [1 ]
机构
[1] Univ Paris 05, Pharmacol Lab, UPRESEA 2510, F-75270 Paris 06, France
[2] Ctr Rech Labs Fournier, Daix, France
关键词
B-2 receptor null mice; bradykinin B-2 receptor antagonist; brain edema; closed head injury; inflammation; neuroprotection;
D O I
10.1089/089771503322385773
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Inhibition of the bradykinin B-2 receptor type (B2R) has been shown to improve neurological outcome in models of focal traumatic brain injury. However, the involvement of B2R in trauma-induced diffuse injury has not yet been explored. This is an important point, since in humans a pattern of diffuse injury is commonly found in severely injured patients and has been associated with a poor neurological outcome and prognosis. Using the non-peptide BY antagonist LF 16-0687 Ms and B2R null (B2R-/-) mice, we investigated the role of B2R in a model of closed head trauma (CHT). LF 16-0687 Ms given 30 min after injury reduced the neurological deficit by 26% and the cerebral edema by 22% when evaluated 4 h after CHT. Neurological function after CHT was improved in B2R-/- mice compared to B2R+/+ mice, although there was no difference in the development of brain edema. Treatment with LF 16-0687 Ms and B2R gene deletion decreased the accumulation of neutrophils at 24 h after CHT (50% and 36%, respectively). In addition, the inducible NO synthase (iNOS) mRNA level increased markedly, and this was reduced by LF 16-0687 Ms. Taken together, these data support a detrimental role of B2R in the development of the neurological deficit and of the inflammatory secondary damage resulting from diffuse traumatic brain injury. Therefore, blockade of bradykinin B-2 receptors might represent an attractive therapeutic approach in the pharmacological treatment of traumatic brain injury.
引用
收藏
页码:841 / 851
页数:11
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