Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Lumenta, DB; Plesnila, N; Kläsner, B; Baethmann, A; Pruneau, D; Schmid-Elsaesser, R; Zausinger, S.
Neuroprotective effects of a postischemic treatment with a bradykinin B2 receptor antagonist in a rat model of temporary focal cerebral ischemia.
Brain Res. 2006; 1069(1):227-234
Doi: 10.1016/j.brainres.2005.11.043
Web of Science
PubMed
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FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Lumenta David Benjamin
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- Abstract:
- Bradykinin, an endogenous nonapeptide produced by activation of the kallikrein-kinin system, promotes neuronal tissue damage as well as disturbances in blood-brain barrier function through activation of B2 receptors. In a rat model of focal cerebral ischemia, blockade of B2 receptors before initiation of ischemia with the B2 receptor antagonist, LF 16-0687 Ms, afforded substantial neuroprotection. In order to assess the potential clinical value of this approach, we evaluated the effect of LF 16-0687 Ms given at reperfusion following focal cerebral ischemia on local cerebral blood flow (LCBF), neurological outcome, and infarct size. Sprague-Dawley rats were subjected to MCA occlusion for 90 min by an intraluminal filament. Animals were assigned to one of four treatment arms (n = 7 each): (1) vehicle, (2) LF 16-0687 Ms (1.0 mg/kg/day), (3) LF 16-0687 Ms (3.0 mg/kg/day), or (4) LF 16-0687 Ms (10.0 mg/kg/day) given at reperfusion and repetitively over 2 days. Neurological recovery was examined daily, and infarct volume was assessed histologically on day 7 after ischemia. Physiological parameters and local CBF were not influenced by the treatment. Significant improvement of neurological outcome was observed on postischemic day 3 in animals receiving 1.0 and 3.0 mg/kg/day of LF 16-0687 Ms (P < 0.05). Inhibition of B2 receptors significantly reduced infarct volume in all treated animals predominantly in the cortex. B2 receptor blockade with LF 16-0687 Ms showed neuroprotective effectiveness even when therapy was initiated upon reperfusion, i.e. 90 min after induction of ischemia. Therefore, blockade of B2 receptors seems to be a promising therapeutic approach after focal cerebral ischemia, which deserves further experimental and clinical evaluation.
- Find related publications in this database (using NLM MeSH Indexing)
- Analysis of Variance -
- Animals -
- Brain Ischemia - drug therapy Brain Ischemia - pathology Brain Ischemia - physiopathology
- Cerebral Infarction - etiology Cerebral Infarction - pathology Cerebral Infarction - prevention and control
- Cerebrovascular Circulation - drug effects
- Disease Models, Animal -
- Dose-Response Relationship, Drug -
- Laser-Doppler Flowmetry - methods
- Male -
- Neuroprotective Agents - therapeutic use
- Quinolines - therapeutic use
- Rats -
- Rats, Sprague-Dawley -
- Recovery of Function - drug effects
- Time Factors -
- Treatment Outcome -
- Find related publications in this database (Keywords)
- cerebral ischemia
- focal
- bradykinin
- bradykinin B-2 receptor
- antagonization
- laser-doppler flowmetry
- neuroprotection