gms | German Medical Science

56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
3èmes journées françaises de Neurochirurgie (SFNC)

Deutsche Gesellschaft für Neurochirurgie e. V.
Société Française de Neurochirurgie

07. bis 11.05.2005, Strasbourg

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Tacrolimus (FK506) significantly reduces local inflammatory response following focal cortical contusion in rats

Tacrolimus (FK 506) reduziert die lokale inflammatorische Reaktion nach fokaler kortikaler Kontusion

Meeting Abstract

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  • corresponding author U. W. Thomale - Neurochirurgische Klinik, Charité - Universitätsmedizin Berlin
  • M. Bender - Neurochirurgische Klinik, Charité - Universitätsmedizin Berlin
  • C. Woiciechowsky - Neurochirurgische Klinik, Charité - Universitätsmedizin Berlin
  • A. W. Unterberg - Neurochirurgische Klinik, Ruprecht-Karls Universität, Heidelberg
  • J. F. Stover - Chirurgische Intensivmedizin, Universitätshospital Zürich, Schweiz

Deutsche Gesellschaft für Neurochirurgie. Société Française de Neurochirurgie. 56. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3èmes journées françaises de Neurochirurgie (SFNC). Strasbourg, 07.-11.05.2005. Düsseldorf, Köln: German Medical Science; 2005. DocP050

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2005/05dgnc0318.shtml

Published: May 4, 2005

© 2005 Thomale et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

Text

Objective

The immunosuppressant drug tacrolimus (FK-506) showed neuroprotective abilities in experimental stroke. In a model of traumatic brain injury pro-inflammatory cytokines were suppressed in cerebrospinal fluid. We investigated the effect of FK506 on immune cell infiltration following controlled cortical impact injury in rats.

Methods

Using 30 Sprague Dawley (300-350g) rats anesthetized with isoflurane a moderate left parietal cortical contusion was applied. Animals received either FK 506 (1mg/kg b.w.) or physiological saline intraperitoneally at 30 minutes after trauma. Brains were removed at 24, 72 hours and 7 days, respectively. Frozen brain sections (7µm) were stained immunehistochemically using ICAM-1, ED-1, Ox-6 and HIS-48 for characterizing immune cell infiltration. The sections were digitized and immune cells were counted within the contusion and in the pericontusional area using a computer analyzing system.

Results

Simultaneously to ICAM-1 expression neutrophil accumulation (HIS-48+ cells) was highest at 72 hours following trauma. FK 506 suppressed significantly ICAM-1 positive cells (p<0.05) similar to the reduction of neutrophil infiltration at 72 hours following trauma. Microglia activation (Ox-6+ cells) revealed highest expression at 72 hours, which was significantly reduced by FK 506 (p<0.01). Macrophage infiltration (ED-1+ cells) increased over time and reached highest intensity at 7 days. Despite a transient significant decrease of ED-1 positive cells at 72 hours (p<0.05) macrophage infiltration was not influenced by tacrolimus at 7 days after contusion.

Conclusions

Tacrolimus (FK506) decreased significantly cellular inflammatory response following focal traumatic brain injury. Further investigations are warrented, whether inhibition of local inflammation results in neuroprotective or deleterious effects on neuronal cell damage.