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69. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Mexikanischen und Kolumbianischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

03.06. - 06.06.2018, Münster

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The role of EphrinB2 in vascular remodeling during chronic cerebral ischemia

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  • Till de Bortoli - Charité - Universitätsmedizin Berlin, Berlin, Deutschland
  • Melina Nieminen-Kelhä - Charité - Universitätsmedizin Berlin, Berlin, Deutschland
  • Irina Kremenetskaia - Charité - Universitätsmedizin Berlin, Berlin, Deutschland
  • Silke Dusatko - Charité - Universitätsmedizin Berlin, Berlin, Deutschland
  • Johannes Woitzik - Charité - Universitätsmedizin Berlin, Berlin, Deutschland
  • Peter Vajkoczy - Charité - Universitätsmedizin Berlin, Berlin, Deutschland
  • Nils Hecht - Charité - Universitätsmedizin Berlin, Berlin, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 69. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Mexikanischen und Kolumbianischen Gesellschaft für Neurochirurgie. Münster, 03.-06.06.2018. Düsseldorf: German Medical Science GMS Publishing House; 2018. DocV055

doi: 10.3205/18dgnc056, urn:nbn:de:0183-18dgnc0567

Published: June 18, 2018

© 2018 de Bortoli et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Objective: Formerly we characterized the process of spontaneous collateral remodeling (arteriogenesis) in a model of chronic cerebral hypoperfusion. Recent evidence in the field of peripheral artery and coronary heart disease research suggests that this process is accompanied by upregulation of the arterial endothelial cell (EC) marker EphrinB2, which controls sprouting of new blood vessels. Therefore, we explored the role of EC EphrinB2 in cerebral collateral remodeling using a transgenic mouse model of chronic cerebral ischemia.

Methods: Chronic cerebral ischemia in adult, male, EC-specific EphrinB2 inducible knock out mice (Efnb2i∆EC) and wildtype littermates (control) was simulated by right-sided internal carotid artery occlusion (ICAO). The Efnb2i∆EC phenotype was confirmed by qPCR and Western Blot. Hemodynamic impairment was quantified by non-invasive Laser Speckle Imaging on days 0, 3, 7, 14 and 21. On day 21, the basal and leptomeningeal angioarchitecture was characterized following Latex/carbon black perfusion.

Results: Over the 21 days, no difference in hemodynamic impairment and -recovery was noted between Efnb2i∆EC and control. However, in Efnb2i∆EC the diameters of all areas of the Circle of Willis were significantly reduced compared to control, particularly in the middle cerebral artery (Efnb2i∆EC 165±26µm, control 189±25µm; *p<0.001), internal carotid artery (Efnb2i∆EC 207±24µm, control 226±29µm; *p<0.001) and basilar artery (Efnb2i∆EC 219±29µm, control 259±21µm; *p<0.001). Further, Efnb2i∆EC mice exhibited a significantly lower number of leptomeningeal anastomoses (Efnb2i∆EC 28±6, control 36±7; *p<0.05) as well as a lower number of leptomeningeal branching points (Efnb2i∆EC 41±15, control 49±10; *p<0.05). Limited leptomeningeal remodeling in Efnb2i∆EC compared to controls was confirmed by a higher relative frequency of small-caliber anastomoses (15-25µm: Efnb2i∆EC 53±15%, control 23±13%; *p<0.01) together with a lower relative frequency of large-caliber anastomoses (35-45µm: Efnb2i∆EC 5±10%, control 20±8%; *p<0.05).

Conclusion: Specific loss of EC EphrinB2 limits outgrowth and remodeling of cerebral collaterals in chronic cerebral hypoperfusion.