Artikel
Age-dependence of arteriogenesis and hemodynamic compensation during chronic cerebral ischemia
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Veröffentlicht: | 16. September 2010 |
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Gliederung
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Objective: Unilateral internal carotid artery occlusion (ICAO) induces spontaneous arteriogenesis in C57/BL6 mice. However, little is known about the impact of age on the capacity for hemodynamic compensation and collateral vessel growth. The present study tests this effect in a model of chronic cerebral hypoperfusion in C57/BL6 mice.
Methods: 40 male C57/BL6 mice, aged 4 to 6 weeks (n=20) and 18 months (n=20) were anaesthetized with Ketamine/Xylazin. In both groups, mild chronic cerebral hypoperfusion was induced through right-sided ICAO (n=10) and compared to sham operated animals (n=10). In order to assess the degree of functional hemodynamic impairment, the cortical cerebrovascular reserve capacity (CVRC) was measured at repeated time points over the course of 21 days with laser speckle contrast analysis (LASCA) imaging. To evaluate morphological arteriogenesis, latex/carbon black angiograms were performed on day 21 after ICAO and evaluated regarding (a) basal vessel diameter, (b) number and diameter of leptomeningeal anastomoses and (c) leptomeningeal mean vascular density.
Results: ICAO in young mice resulted in a significant decrease of the ipsilateral CVRC on day 0 and functional compensation by day 3. Conversely, 18-month old mice demonstrated functional compensation merely within 14 days after the procedure. Between the sham groups, no significant difference was found.
21 days after ICAO, the basal vessel diameter was significantly increased in the anterior circulation of both young and old animals: While young animals showed a diameter increase in both the ICA (ICAO vs. Sham: 230±17µm vs. 193±15 µm) and anterior cerebral artery (ACA) (ICAO vs. Sham: 236±23 µm vs. 176±14 µm), the 18-month old animals developed increased vessel diameters only in the ACA (ICAO vs. Sham: 210±25 µm vs. 177±28 µm) while the ICA diameters remained unchanged (ICAO vs. Sham: 191±24 µm vs. 195±19 µm). In both groups, the number and diameter of leptomeningeal anastomoses after ICAO was significantly increased with no difference in the mean vascular density of the leptomeningeal vasculature.
Conclusions: Increased age may cause poor functional and morphological compensation of chronic hemodynamic perfusion deficits of the brain. This finding underlines the importance of age as a significant factor regarding spontaneous collateral vessel growth during chronic cerebral ischemia in a model for further investigation of arteriogenic factors in transgenic mice.