Artikel
Intravascular leukocyte activation precedes intraparenchymal inflammatory reaction in the central nervous system after experimental subarachnoid hemorrhage
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Veröffentlicht: | 4. Juni 2012 |
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Objective: Inflammatory mechanisms have become an interesting target for analysis of early and delayed brain injury after acute subarachnoid hemorrhage (aSAH). Our group could demonstrate an intraparenchymal cellular inflammatory reaction after SAH in the central nervous system (CNS), which peaked 7–14 days after the bleeding. This reaction was accompanied by signs of axonal injury (extracellular amyloid precursor protein), which followed the same time-course and expression pattern. To evaluate, if preceding intravascular inflammatory processes can be shown, as a causal chain, a chronic cranial window model was applied.
Methods: Mice (n=6 per group) underwent experimental subarachnoid hemorrhage through endovascular perforation technique. A chronic cranial window was established and rolling and sticking leukocytes were counted in vivo using fluorescence imaging techniques. In a second set of experiments immunohistochemical stanings were performed to visualize intraparenchymal leukocytes in the CNS after experimental aSAH
Results: An increase in rolling and sticking leukocytes was documented directly after aSAH (Day 0: 7.8±0.3 vs. 5.2±0.3; SAH/SHAM; n/min; mean ± SEM), as well as in the following days (Day 2: 10.7±0.6 vs. 8.0±0.5; Day 4: 11.2±0.5 vs. 7.4±0.5). Accordingly, the number of sticking leukocytes was elevated during the same time interval (Day 0: 364±28 vs. 287±39; Day 2: 528±36 vs. 405±22; Day 4: 483±10 vs. 444±29; SAH/SHAM; n/mm2; mean ± SEM). A significantly elevated number of intraparenchymal leukocytes could not be detected.
Conclusions: An intravascular inflammatory reaction preceded the intraparenchymal inflammatory response after aSAH. Despite elevated rolling and sticking activity of intravascular leukocytes no leukocyte trafficking into the brain parenchyma could be shown, supposing an indirect mechanism (e.g. by cytokines) or a co-incidence. To relate the intravascular to the intraparenchymal inflammatory reaction and to exclude a co-incidence, additional experiments with ICAM and PSGL knockout animals will be performed.