gms | German Medical Science

59th Annual Meeting of the German Society of Neurosurgery (DGNC)
3rd Joint Meeting with the Italian Neurosurgical Society (SINch)

German Society of Neurosurgery (DGNC)

1 - 4 June 2008, Würzburg

Neuroprotective effects of continuous norepinephrine (NE) infusion following Controlled Cortical Impact Injury (CCII) are at least in part mediated by induction of glutamate transporter proteins and increased extracellular glutamate uptake

Die neuroprotektiven Effekte einer kontinuierlichen Noradrenalininfusion nach Controlled Cortical Impact Injury (CCII) beruhen zumindest zum Teil auf der verstärkten Expression glialer Glutamattransporter und einer erhöhten extrazellulären Glutamataufnahme

Meeting Abstract

  • corresponding author S. Schreiber - Klinik für Neurochirurgie, Helios Klinikum Berlin
  • J. F. Stover - Abteilung für Chirurgische Intensivmedizin, Universitätsspital Zürich
  • A. von Deimling - Institut für Neuropathologie, Universitätsklinikum Heidelberg
  • F. K. van Landeghem - Institut für Neuropathologie, Charite - Universitätsmedizin Berlin

Deutsche Gesellschaft für Neurochirurgie. Società Italiana di Neurochirurgia. 59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch). Würzburg, 01.-04.06.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. DocP 113

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

Published: May 30, 2008

© 2008 Schreiber 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: The role of continuous NE infusion following traumatic brain injury is still a matter of debate as it might have both beneficial and detrimental effects. In previous studies we have learned that low-dose NE infusion (0.15 μg/kg/min) results in decreased cortical contusion volume 48 hours after CCII in rats. This neuroprotective effect was not observed in rats receiving medium (0.3 μg/kg/min) or high (1 μg/kg/min) NE doses, whereas intraparenchymal hemorrhage was significantly increased in these animals. There is evidence for an α1 receptor mediated induction of glutamate transporter proteins in cell cultures as well as for better neurological outcome in brain injured patients receiving α1 receptor agonists. Therefore, the goal of the present study was to elucidate whether continuous low dose NE infusion attenuates posttraumatic glutamate excitotoxicity by the induction of glutamate transporter protein expression in vivo.

Methods: 108 adult male Spraque-Dawley rats, were anaesthetized with isoflurane before moderate CCII was produced to the right parietotemporal cortex. Starting at 4 hours following CCII rats were continuously infused with 0.15 μg/kg/min NE or NaCl via ALZET® osmotic pumps. Animals were sacrificed after 48 hours, 7 days or 4 weeks and evaluated either for cortical contusion volume or glutamate transporter protein expression. MABP, blood glucose and blood gases were determined repetitively. Extracellular concentrations of glucose, glutamate, lactate, pyruvate and glycerol were determined 4, 24 and 48 hours following CCII via microdialysis in an additional group of animals (n=60).

Results: Contusion volume at 48 hours following CCII was significantly decreased by 40% in NE treated animals, but not at 7 days and 4 weeks after CCII. NE treatment led to significantly reduced extracellular glutamate (41,1±16,1 µmol/l vs. 13,81±5,05 µmol/l, p<0,05) and lactate (3,29±1,26 mmol/l vs. 1,99±0,64 mmol/l, p<0,05) concentrations at 24 and 48 hours after trauma. Expression of glutamate transporter proteins EAAT1 and EAAT2 was significantly increased 48 hours and 7 days following CCII by 5-10%.

Conclusions: Continuous low dose NE infusion is neuroprotektive following CCII. This effect is at least in part mediated by an increase in glutamate transporter protein expression, which results in decreased extracellular glutamate concentrations.