gms | German Medical Science

60th Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Benelux countries and Bulgaria

German Society of Neurosurgery (DGNC)

24 - 27 May 2009, Münster

Studies on the gene expression of the kallikrein-kinin System (KKS) in brain arteries and tissue in a rat model of focal cerebral ischemia

Meeting Abstract

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  • N.E. Lapina - Neurochirurgische Forschung Mannheim
  • N. Weinzierl - Neurochirurgische Forschung Mannheim
  • L. Schilling - Neurochirurgische Forschung Mannheim

Deutsche Gesellschaft für Neurochirurgie. 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien. Münster, 24.-27.05.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. DocP09-12

DOI: 10.3205/09dgnc352, URN: urn:nbn:de:0183-09dgnc3529

Published: May 20, 2009

© 2009 Lapina et al.
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Outline

Text

Objective: Bradykinin (Bk) is the major metabolite of the KKS acting upon B2 receptors which are constitutively expressed and B1 receptors following their de novo expression. A complete KKS is present in the central nervous system, and evidence is also available in favor of vascular expression. Under pathological conditions the expression of the various components of the KKS may undergo adaptive responses. In the present study we performed an in depth analysis of the KKS gene expression in brain tissue in an established model of focal ischemia and compared it with the alterations of expression in the arterial wall.

Methods: Male normotensive rats were anesthetized with halothane and underwent right-sided middle cerebral artery occlusion (MCAO) for 24 h (permanent ischemia) or for 2 h followed by reperfusion (transient ischemia). Animals were killed after 24 h and the brain and both MCAs isolated. From each brain serial sections (thickness, 20 µm) were obtained for silver nitrate staining to determine cerebral infarct volume and hemispheric swelling. Total RNA was extracted from ischemic and non-ischemic (contralateral) hemispheric tissue and from individual MCAs. After reverse transcription real time quantitative PCR (qPCR) was performed to describe the changes of gene expressions of different components of the KKS (B1-receptor, B2-receptor, angiotensin converting enzyme (ACE), kininogen, kallikrein). Results were analyzed using ΔΔCT methodology with elongation factor (EF)-1 and GAPDH as house keeping genes. Data are presented as mean ±SD.

Results: The volume of ischemic damage after correction for swelling did not differ between animals with transient (308±34 mm3) and permanent MCAO (312±91 mm3). The expression of EF-1 and GAPDH did not differ between both hemispheres. After transient MCAO only the B1 receptor mRNA was significantly increased in brain tissue (ΔΔCT: 4.37±0.88, i.e. and ~21 fold increase). In contrast, after permanent occlusion the mRNA encoding for the B2 receptor, ACE, and kininogen were significantly increased in the vessel wall (ΔΔCT for B2: 7.1±2.6, for ACE: 5.1±1.8; for kininogen: 6.4±2.5).

Conclusions: The present study shows in a model of focal brain ischemia adaptive changes in gene expression of the entire KKS. These changes appear to be more pronounced (I) in permanent vs. transient MCAO, and (ii) in the arterial wall vs. the affected brain tissue. These observations indicate a differential response upon ischemia in these compartments.