Response to Letter by Tsuda
We appreciate the comments and interest of Dr Tsuda regarding our article. We did not determine the contents of bradykinin and catecholamines in the infarcted regions of bradykinin receptor 1 knockout mice and wild-type controls in our study, but agree that the relationship between the kallikrein/kinin-system and sympathetic mediators could be relevant for the pathophysiology of ischemic stroke. Gröger and coworkers described significantly elevated tissue bradykinin levels within infarcts after 45 minutes of middle cerebral artery occlusion in wild-type mice.1 Moreover, basal brain levels of bradykinin did not differ between wild-type and bradykinin receptor 2 knockout mice, but were not analyzed in the latter after middle cerebral artery occlusion. Their study also did not include bradykinin receptor 1 knockout mice. Catecholamines might also play an important role in mediating stroke-induced immunodeficiency leading to impaired antibacterial immune responses and increased rates of infections after focal cerebral ischemia.2 Whether this phenomenon is linked to the kallikrein/kinin-system is unknown at present.
Gröger M, Lebesgue D, Pruneau D, Relton J, Kim SW, Nussberger J, Plesnila N. Release of bradykinin and expression of kinin B2 receptors in the brain: role for cell death and brain edema formation after focal cerebral ischemia in mice. J Cereb Blood Flow Metab. 2005; 25: 978–989.
Prass K, Meisel C, Höflich C, Braun J, Halle E, Wolf T, Ruscher K, Victorov IV, Priller J, Dirnagl U, Volk HD, Meisel A. Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation. J Exp Med. 2003; 198: 725–736.