gms | German Medical Science

58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

26. bis 29.04.2007, Leipzig

Induction of GLT-1 by ceftriaxone reduces neuronal activity and affects neurometabolic coupling of cortical glutamate clearance in isoflurane-anaesthetized rats

Die Ceftriaxon-vermittelte Induktion von GLT-1 vermindert neuronale Spontanaktivität und beeinflusst die neurometabolische Kopplung der Glutamat-Clearance in Isofluran-anaesthesierten Ratten

Meeting Abstract

  • corresponding author J. Yan - Neurochirurgische Klinik, Universitätsklinikum Heidelberg, Heidelberg
  • P. Hoepffner - Neurochirurgische Klinik, Universitätsklinikum Heidelberg, Heidelberg
  • A. Unterberg - Neurochirurgische Klinik, Universitätsklinikum Heidelberg, Heidelberg
  • K. Kiening - Neurochirurgische Klinik, Universitätsklinikum Heidelberg, Heidelberg
  • O. Sakowitz - Neurochirurgische Klinik, Universitätsklinikum Heidelberg, Heidelberg

Deutsche Gesellschaft für Neurochirurgie. 58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC). Leipzig, 26.-29.04.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. DocFR.03.09

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2007/07dgnc083.shtml

Veröffentlicht: 11. April 2007

© 2007 Yan 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 vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: Excessive glutamate concentrations may lead to excitotoxic secondary brain injury. Physiological extracellular concentrations of glutamate are maintained by active transport through glial membrane proteins, e.g. GLT-1. Betalactam-antibiotics, such as ceftriaxone (CTX) are known to increase GLT-1 expression in vivo. Does this mechanism improve cerebral glutamate clearance and associated neurometabolism?

Methods: In total, 35 male Sprague-Dawley rats (317±35g) were pretreated over 5 days, receiving either CTX (200mg/kg/d, i.p.) or saline. Through a craniotomy window, a microdialysis catheter (CMA/12, 2mm, 100kD) was inserted into non-traumatized tissue. In reverse microdialysis-technique, 35µM glutamate followed by 10-1000µM DL-threo-beta-benzyloxyaspartate (DL-TBOA; non-competetive GLT-1 antagonist) was infused cortically. Twenty-minute samples were collected and e.c. concentrations of glutamate, glucose, lactate and pyruvate were determine ed byspectrophotometry. Systemic blood pressure, arterial blood gases, core temperature and EEG were monitored continuously. Differences were assumed to be significant at p<0.05.

Results: The vital signs remained stable in all animals. Under similar levels of anaesthesia, alpha- and beta-EEG-activity was reduced in the treatment group (p<0.05). Glutamate infusion increased EEG-activity in control animals, an effect seen with DL-TBOA only in the CTX group. In both groups cortical glutamate was cleared completely, though associated glycolysis was lower in pretreated animals (e.c. lactate: 119±19 vs 106±17%, p<0.1). In these, anaerobic metabolism was increased upon DL-TBOA (lactate/pyruvate-ratio: 135±13 vs 88±11%, p<0.05).

Conclusions: CTX-induced expression of GLT-1 reduces neuronal activity, responsiveness to cortical glutamate infusion and neurometabolic coupling of glutamate-clearance in isoflurane-anaesthetized rats. Whether this mechanism results in post-traumatic neuroprotection is currently being investigated.