Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Zausinger, S; Lumenta, DB; Pruneau, D; Schmid-Elsaesser, R; Plesnila, N; Baethmann, A.
Effects of LF 16-0687 Ms, a bradykinin B(2) receptor antagonist, on brain edema formation and tissue damage in a rat model of temporary focal cerebral ischemia.
Brain Res. 2002; 950(1-2):268-278
Doi: 10.1016/S0006-8993(02)03053-6
Web of Science
PubMed
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- Co-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 B(2) receptors. LF 16-0687 Ms, a non-peptide competitive bradykinin B(2) receptor antagonist, was recently found to decrease brain swelling in various models of traumatic brain injury. We have investigated the influence of LF 16-0687 Ms on the edema formation, neurological outcome, and infarct size in temporary focal cerebral ischemia in rats. Sprague-Dawley rats were subjected to MCA occlusion for 90 min by an intraluminal filament. Local CBF was bilaterally recorded by laser Doppler flowmetry. Study I: animals were assigned to one of three treatment arms (n=11 each): (a) vehicle, (b) LF 16-0687 Ms (12.0 mg/kg per day), or (c) LF 16-0687 Ms (36.0 mg/kg per day) given repetitively s.c. over 3 days. The neurological recovery was examined daily. The infarct volume was assessed histologically 7 days after ischemia. Study II: brain swelling and bilateral hemispheric water content were determined at 48 h post ischemia in eight rats, subjected to the low dose regimen as described above, and in eight vehicle-treated control animals. All treated animals showed tendency to exhibit improved neurological recovery throughout the observation period as compared to the vehicle-treated controls, while this improvement was only significant within the low dose group from postischemic days 3 to 4. Low dose LF 16-0687 Ms significantly attenuated the total and cortical infarct volume by 50 and 80%, respectively. Furthermore, postischemic swelling (-62%) and increase in water content of the infarcted brain hemisphere (-60.5%) was significantly inhibited. The present findings provide strong evidence for an involvement of bradykinin-mediated secondary brain damage following from focal cerebral ischemia. Accordingly, specific inhibition of bradykinin B(2) receptors by LF 16-0687 Ms attenuated postischemic brain swelling, improved the functional neurological recovery, and limited ischemic tissue damage, raising its potential for clinical evaluation in patients with acute stroke.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Brain - drug effects Brain - pathology
- Brain Edema - drug therapy Brain Edema - pathology Brain Edema - physiopathology
- Brain Ischemia - drug therapy Brain Ischemia - pathology Brain Ischemia - physiopathology
- Disease Models, Animal -
- Male -
- Quinolines - pharmacology Quinolines - therapeutic use
- Rats -
- Rats, Sprague-Dawley -
- Receptor, Bradykinin B2 -
- Receptors, Bradykinin - antagonists and inhibitors Receptors, Bradykinin - physiology
- Find related publications in this database (Keywords)
- cerebral ischemia, focal
- bradykinin
- bradykinin B-2
- receptor antagonization
- laser-Doppler flowmetry
- neuroprotection
- brain edema