gms | German Medical Science

64. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

26. - 29. Mai 2013, Düsseldorf

Effect of the sphingosine-1-phosphate receptor modulator FTY720 on the outcome in a mouse model of focal cortical cryolesion

Meeting Abstract

  • Nelli Hennig - Neurochirurgische Klinik, Universitätsklinikum Würzburg, Würzburg, Deutschland
  • Christiane Albert-Weissenberger - Neurologische Klinik, Universitätsklinikum Würzburg, Würzburg, Deutschland
  • Christoph Kleinschnitz - Neurologische Klinik, Universitätsklinikum Würzburg, Würzburg, Deutschland
  • Anna-Leena Sirén - Neurochirurgische Klinik, Universitätsklinikum Würzburg, Würzburg, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 64. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Düsseldorf, 26.-29.05.2013. Düsseldorf: German Medical Science GMS Publishing House; 2013. DocP 070

doi: 10.3205/13dgnc487, urn:nbn:de:0183-13dgnc4870

Veröffentlicht: 21. Mai 2013

© 2013 Hennig 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 vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: Traumatic brain injury (TBI), a leading cause of death and disability, characteristically results in acute inflammation and massive brain edema. The molecular mechanisms of edema formation after TBI have not been fully elucidated and the contribution of the acute inflammatory response to brain damage after TBI is not well established. The immune-modulatory sphingosine-1-phosphate receptor (S1PR) agonist, FTY720 Phosphate (active metabolite of FTY720) down-regulates lymphocyte trafficking by binding to S1PRs, which are strongly expressed in CNS and lymphoid tissue favoring especially T-cell retention in lymph nodes. In the present study we investigated the effect of FTY720 on the breakdown of the blood brain barrier, brain edema formation, immune cell infiltration and development of brain injury after focal (cortical cryolesion) in mice.

Method: 6-week old C57BL/6 mice received intraperitoneally 1 mg/kg FTY720 or vehicle immediately before the induction of brain injury by cortical cryolesion. We then assessed the effects of FTY720-treatment 24 h after injury induction on the blood brain barrier and brain edema formation by quantification of Evan’s blue extravasation and wet-to-dry weight ratio, respectively. Immune cell infiltration was determined by immune-histochemical stainings and lesion volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain slices.

Results: Treatment with FTY720, reduced immune cell infiltration of neutrophils (vehicle-treated mice 253.0±87.27 n=10 versus FTY720-treated mice 76.18±12.95 n=11, P<0.05) and macrophages (vehicle-treated mice 197.2±49.47 n=10 versus FTY720-treated mice 100.3±19.24 n=11, P>0.05) into the brain but had no effect on the lesion-induced breakdown of the blood brain barrier (Evan’s blue extravasation), brain edema formation assessed by wet-to-dry weight ratio or on brain lesion volumes calculated from TTC-stained brain slices.

Conclusions: In a mouse model of cortical cryolesion post-traumatic treatment with FTY720 reduces influx of immune cells in the damaged brain, but does not affect brain edema and focal injury.

This study is supported by an unrestricted grant from the Novartis Pharma GmbH, Nürnberg, Germany.