gms | German Medical Science

57th Annual Meeting of the German Society of Neurosurgery
Joint Meeting with the Japanese Neurosurgical Society

German Society of Neurosurgery (DGNC)

11 - 14 May, Essen

Combination with NMDA antagonists optimizes fibrinolytic therapy of experimental intracerebral hemorrhages

Die Kombination mit NMDA-Antagonisten zur Optimierung der fibrinolytischen Therapie experimenteller, intrazerebraler Blutungen

Meeting Abstract

  • corresponding author R. Thiex - Neurochirurgische Klinik, Universitätsklinikum der RWTH Aachen
  • V. Rohde - Neurochirurgische Klinik, Universitätsklinikum der RWTH Aachen
  • J. Weis - Institut für Neuropathologie, Universitätsklinikum der RWTH Aachen
  • T. Krings - Abteilung für Neuroradiologie, Universitätsklinikum der RWTH Aachen
  • S. Barreiro - Neurochirurgische Klinik, Universitätsklinikum der RWTH Aachen
  • F. Yakisikli-Alemi - Neurochirurgische Klinik, Universitätsklinikum der RWTH Aachen
  • J.M. Gilsbach - Neurochirurgische Klinik, Universitätsklinikum der RWTH Aachen

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 57. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie. Essen, 11.-14.05.2006. Düsseldorf, Köln: German Medical Science; 2006. DocP 10.151

The electronic version of this article is the complete one and can be found online at:

Published: May 8, 2006

© 2006 Thiex et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Objective: Tissue plasminogen activator (tPA) exerts pleiotropic actions in the brain including regulation of vasoactivity, amplification of calcium conductance by cleavage of the N-methyl-D-aspartate (NMDA) receptor subunit, and activation of metalloproteinases that increase excitotoxicity, damage the blood brain barrier, and worsen edema. We investigated whether the non-competitive NMDA antagonist MK801 can be used as adjuvant therapy in combination with rtPA to attenuate the unfavourable delayed edema formation and inflammation after rtPA-therapy in experimental porcine intracerebral hemorrhages.

Methods: In 20 pigs, MK801 was administered i.v. (0.3 mg/kg) immediately after hematoma induction, on the 1st and 3rd postoperative day. 10 of the 20 pigs were randomly assigned to fibrinolytic therapy with rtPA, whereas the hematomas of the remaining 10 control animals followed their natural course of resorption. The degree of edema formation was evaluated by MRI planimetry on days 0, 4, and 10 after hematoma induction and was correlated to the histopathological changes found at autopsy. The 9 pigs treated with rtPA only of our previous series served as a control to rtPA-induced alterations.

Results: In the animals treated both with MK801 and rtPA (n=10), the mean perihematomal edema size on FLAIR images had not significantly increased on days 4 (p<0.08) and 10 (p<0.35) after hematoma induction. In the 10 control animals, the increase in mean perifocal edema was significant after 4 days (p<0.02) and non-significant after 10 days (p<0.09).

Conclusions: MK801 reduces rtPA-induced delayed edema formation and inflammatory response. The fibrinolytic potential of rtPA can only be beneficial in the combination with agents such as MK801 that block the neurotoxic properties of rtPA.