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

Stimulation of angio- and arteriogenesis and cerebral blood flow in a rat model of chronic mild impairment of the cerebral perfusion

Stimulation von Angio- ung Arteriogenese und des zerebralen Blutflusses in einem Rattenmodell chronisch leicht verminderter zerebraler Perfusion

Meeting Abstract

Suche in Medline nach

  • corresponding author Ulf Schneider - Neurochirurgische Klinik, University Hospital Mannheim, University of Heidelberg, Mannheim
  • J. Woitzik - Neurochirurgische Klinik, University Hospital Mannheim, University of Heidelberg, Mannheim
  • L. Schilling - Neurochirurgische Klinik, University Hospital Mannheim, University of Heidelberg, Mannheim

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. DocP 01.4

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2004/04dgnc0287.shtml

Veröffentlicht: 23. April 2004

© 2004 Schneider 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

To study the influence of long-term therapy with a recombinant granulocyte-macrophage colony stimulating factor (GM-CSF, Leukomax®) on regional cerebral blood flow (rCBF) and the morphology of the cerebral microvascular network in an animal model of chronic mild cerebral hypoperfusion.

Methods

Experiments were performed in male Sprague-Dawley rats with surgery and measurements performed under isoflurane anaesthesia. On day one, sagittal grooves were drilled over both temporal hemispheres outreaching the coronal and lambda suture. In these grooves rCBF was repeatedly measured using scanning Laser-Doppler flowmetry (LDF) in at least 80 different points. Animals underwent right-sided intraluminal occlusion of the internal carotid artery (ICA) on day one, followed by left-sided occlusion on day seven. The animals received a subcutaneous injection of 10 μg/kg Leukomax (R) (treatment group) or 0.2 ml/kg saline (control group) once a day for seven weeks starting on day one. LDF measurements were performed weekly. After seven weeks the rats were perfused with Evan's Blue (EB). Serially cut coronal brain sections were prepared and scanned for capillary density using EB-fluorescence. Adjacent brain sections were with Alpha-smooth muscle actin (alpha-SMA) antibody to evaluate the number of arterioles and small arteries.

Results

The acute drop of CBF induced by ICA occlusion on days one and seven did not differ between treated and control animals. The CBF recovered within a week after ICA occlusion in control animals, but rose steadily above basal levels in GM-CSF treated animals. At the end of the experiments, values were 35% higher than baseline (p<0.05). There were no signs of apoptosis, or decrease in cell density in the hippocampus at the end of the experiments, indicating that no ischemic brain damage had occurred. Capillary density was slightly yet significantly higher in motorcortex areas of treated animals (p<o.o5 vs. control group). The number of alpha-SMA positive vessels increased throughout all brain sections (+35% compared to control animals) after seven-week treatment and was up to 60% higher in individual brain regions.

Conclusions

These results suggest that systemic application of GM-CSF results in enhanced arteriogenesis and stimulation of angiogenesis in a state of chronic mild cerebral hypoperfusion. The underlying mechanisms and the role of macrophages are currently under investigation. The present results may also be clinically relevant and promise a new therapeutic approach, in states of, yet compensated compromised cerebral hypoperfusion, such as, ICA stenosis.