gms | German Medical Science

65th Annual Meeting of the German Society of Neurosurgery (DGNC)

German Society of Neurosurgery (DGNC)

11 - 14 May 2014, Dresden

Glibenclamide reduces secondary brain damage after experimental traumatic brain injury

Meeting Abstract

  • Katharina Hackenberg - Neurochirurgische Universitätsklinik, Universitätsklinikum Heidelberg
  • Klaus Zweckberger - Neurochirurgische Universitätsklinik, Universitätsklinikum Heidelberg
  • Oliver Sakowitz - Neurochirurgische Universitätsklinik, Universitätsklinikum Heidelberg
  • Carla Jung - Neurochirurgische Universitätsklinik, Universitätsklinikum Heidelberg
  • Karl Kiening - Neurochirurgische Universitätsklinik, Universitätsklinikum Heidelberg
  • Andreas Unterberg - Neurochirurgische Universitätsklinik, Universitätsklinikum Heidelberg

Deutsche Gesellschaft für Neurochirurgie. 65. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Dresden, 11.-14.05.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. DocP 110

doi: 10.3205/14dgnc506, urn:nbn:de:0183-14dgnc5060

Published: May 13, 2014

© 2014 Hackenberg 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: Under hypoxic conditions Sulfonylurea receptor 1 (SUR1) regulated non-selective cation channels are generated in astrocytes, neurons and endothelial cells. ATP depletion causes depolarization and opening of these channels leading to cytotoxic edema. Blocking of SUR1 with low-dose glibenclamide reduces edema, contusion volume and mortality rate in models of experimental cerebral stroke and spinal cord injury. Therefore, glibenclamide might also prevent the development of secondary brain damage after experimental traumatic brain injury (TBI).

Method: Experimental TBI was performed by a controlled cortical impact injury (CCI) in 68 Sprague-Dawley rats. Glibenclamide or vehicle was administered as a subcutaneous bolus 15 min after CCI and via diffusion pumps over 7 days. Acute (patho-) physiological changes (ICP, cerebral metabolism, EEG activity) were monitored over 180 min following trauma. 24 h after CCI brain water content was assessed gravimetrically. Contusion volume depicted by MRI scans and neurological function were quantified 8 h, 48 h, 72 h and 7 days following CCI.

Results: In comparison to baseline levels ICP increased significantly after trauma. Extracellular (ec) glucose concentrations dropped to a “close to zero” level 30 min after CCI, but recovered subsequently. L/P ratio and glutamate concentrations (ec) rose significantly during the observation time. In EEG monitoring average frequency was significantly decreased after CCI compared to sham-operated animals. Number and duration of epileptic seizures were declined in glibenclamide treated animals, but these results did not reach significance. Due to the administration of glibenclamide brain water content was reduced significantly 24 h after TBI (80.47 ± 0.37% vs. 80.83 ± 0.44%, p<0.05). Contusion volumes increased continuously within the first 72 h and diminished 7 days after CCI. At each point in time contusion volume could be decreased significantly in rats treated with glibenclamide compared to controls (8h: 158.0 ± 36.8 mm3 vs. 264.1 ± 44.4 mm3, p<0.001; 24h: 172.5 ± 38.7 mm3 vs. 299.2 ± 64.0 mm3, p<0.001; 72h: 211.1 ± 41.0 mm3 vs. 309.8 ± 64.4 mm3, p<0.001; 7d: 107.1 ± 21.3 mm3 vs. 164.0 ± 29.0 mm3, p<0.005). Neurological function, however, was not influenced by glibenclamide during the first 7 days following CCI.

Conclusions: In summary, treatment with glibenclamide could significantly reduce brain edema and contusion volume after CCI. Therefore, it might offer a promising treatment option for patients with TBI.