gms | German Medical Science

55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

25. bis 28.04.2004, Köln

Subarachnoid hemorrhage in rats – Neuroprotective efficacy of bradykinin B2 receptor blockade

Experimentelle Subarachnoidalblutung bei Ratten - neuroprotektive Effekte der Blockade von Bradykinin-B2-Rezeptoren

Meeting Abstract

  • corresponding author Stefan Zausinger - Neurochirurgische Klinik, Klinikum Großhadern, Ludwig-Maximilians-Universität, München
  • S. Sporer - Institut für Chirurgische Forschung, Klinikum Großhadern, Ludwig-Maximilians-Universität, München
  • S. C. Thal - Institut für Chirurgische Forschung, Klinikum Großhadern, Ludwig-Maximilians-Universität, München
  • J.-C. Tonn - Neurochirurgische Klinik, Klinikum Großhadern, Ludwig-Maximilians-Universität, München
  • R. Schmid-Elsaesser - Neurochirurgische Klinik, Klinikum Großhadern, Ludwig-Maximilians-Universität, München

Deutsche Gesellschaft für Neurochirurgie. Ungarische Gesellschaft für Neurochirurgie. 55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie. Köln, 25.-28.04.2004. Düsseldorf, Köln: German Medical Science; 2004. DocDI.04.02

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2004/04dgnc0180.shtml

Veröffentlicht: 23. April 2004

© 2004 Zausinger et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective

Increased ICP and decreased CBF leading to global cerebral ischemia are the primary causes of death after severe subarachnoid hemorrhage (SAH). One reason for the dramatic initial increase of ICP is the rapidly developing cerebral edema as a result of breakdown of cerebral autoregulation and the blood-brain barrier, constituting an independent risk factor for mortality and poor outcome. Bradykinin, an active peptide of the kallikrein-kinin system has been found to enhance brain edema formation, mediated by bradykinin B2-receptors. LF 16-0687, a novel bradykinin B2 receptor antagonist decreased brain swelling in various models of traumatic and ischemic brain injury. We investigated the influence of LF 16-0687 in a rat model of SAH on ICP, CBF, neurological recovery and evolution of brain edema.

Methods

Twenty-eight rats were subjected to SAH by an endovascular filament. ICP and bilateral CBF were continuously recorded by a parenchymal probe and Laser Doppler flowmetry. Animals were randomly assigned to 3 groups: (a) vehicle, (b) LF 16-0687 s.c. (3 mg/kg), given 30 min before and 6 hours after SAH or (c) LF 16-0687 s.c. (3 mg/kg), given 30 min and 6 hours after SAH. Cerebral water content and functional recovery were assessed 24 hours after SAH at the maximum of brain edema evolution.

Results

SAH resulted in an immediate increase of ICP up to ~60 mmHg initially and ~30 mmHg for the following 90 min without significant differences between groups. Bilateral CBF fell by over 80% with partial recovery without differences between groups. Blockade of bradykinin B2 receptors with treatment started before SAH (group b) afforded significant attenuation of brain water content after 24 hours (79.1 ± 0.07 % vs. control: 79.8 ± 0.3 %). Furthermore, this group exhibited significantly better neurological recovery after 24 hours (group b: 5±0 pts. vs. control: 24±7 pts.).

Conclusions

The present findings provide evidence for an involvement of the kallikrein-kinin system and of bradykinin, its active metabolite, in evolution of brain edema after SAH. Our results demonstrate that blocking of bradykinin B2 receptors by LF 16-0687 before SAH attenuates increase of brain water content. Furthermore, pretreatment improved neurological recovery in the early post-SAH period. Failure of treatment started after SAH warrants further experiments with higher dosage or i.v. application.