Artikel
Pattern and time course of iNOS expression in a rat double hemorrhage model – what functional role does it play in developing cerebral vasospasm?
Die iNOS Expression nach experimenteller SAB im Doppelblutungsmodell der Ratte – welche funktionelle Bedeutung hat dies für die Entwicklung des zerebralen Vasospasmus?
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Autoren
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R. Gerlach
- Klinik für Neurochirurgie der Johann-Wolfgang-Goethe-Universität Frankfurt/ Main
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H. Vatter
- Klinik für Neurochirurgie der Johann-Wolfgang-Goethe-Universität Frankfurt/ Main
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G. Demel
- Klinik für Neurochirurgie der Johann-Wolfgang-Goethe-Universität Frankfurt/ Main
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J. Konczalla
- Klinik für Neurochirurgie der Johann-Wolfgang-Goethe-Universität Frankfurt/ Main
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A. Raabe
- Klinik für Neurochirurgie der Johann-Wolfgang-Goethe-Universität Frankfurt/ Main
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V. Seifert
- Klinik für Neurochirurgie der Johann-Wolfgang-Goethe-Universität Frankfurt/ Main
| Veröffentlicht: | 8. Mai 2006 |
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Gliederung
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Objective: Source and time course of inducible nitric oxide synthase (iNOS) expression and its functional involvement in cerebral vasospasm (VSP) after subarachnoid hemorrhage (SAH) is still a matter of debate. Therefore the aim of this study was to correlate the iNOS expression to the time course of VSP after experimental SAH using a rat double hemorrhage model.
Methods: Double hemorrhage was applyied using autologous blood to Sprague Dawley rats after cisternal puncture and removal of 0.1 ml CSF. Second hemorrhage followed 12h later using the same experimental setting. VSP and the reduction of the cerebral blood flow (CBF) was assessed by MR perfusion weighted imaging (PWI) on the days 3 (d3) and 5 (d5). Brain stem together with the basilar arteries (BA) was dissected from the animals on day 2, 3, 5 and 7, prepared for molecular investigations or embedded for immunohistochemical staining. Staining was performed with an antibody against the iNOS (monoclonal antibody C11, Santa Cruz). iNOS mRNA expression was determined on day 2 (n=12), 3 (n=5), 5 (n=5) and 7 (n=4) after first hemorrhage by semiquantitative PCR using GAPDH as internal standard. Sham operated animals were used as controls (n=14).
Results: Immunohistochemical staining for iNOS was not significantly changed in the endothelium and smooth muscle layer of the BA and in adjacent brain stem on day 3 and 5 compared to the control. No iNOS mRNA expression was determined in control animals, but increased in SAH animals on day 2 with the highest expression on day 3 followed by a decrease on day 5 and 7. Relative regional cerebral blood flow (CBF) was reduced to 67% on day (d) 3 and to 38% on d5 after SAH compared to the control.
Conclusions: iNOS mRNA expression peaks on day 3 and therefore parallels the time course of decreased CBF in this double hemorhage model. However, since increased iNOS expression is not followed by significant changes in protein concentration, it seems to be rather an early unspecific response to autologous blood, than a pathogenetic factor of VSP.
