gms | German Medical Science

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

German Society of Neurosurgery (DGNC)

11 - 14 May 2014, Dresden

Activity of pyruvate dehydrogenase-enzyme in hemisphere and hippocampus of experimental subarachnoid hemorrhage: reduction strongly suggests a derangement of oxidative metabolism

Meeting Abstract

  • Nadine Willner - Klinik für Neurochirurgie, Universitätsklinikum Würzburg
  • Hannah Füllgraf - Klinik für Neurochirurgie, Universitätsklinikum Würzburg
  • Christian Stetter - Klinik für Neurochirurgie, Universitätsklinikum Würzburg
  • Stefan Köhler - Klinik für Neurochirurgie, Universitätsklinikum Würzburg
  • Ralf-Ingo Ernestus - Klinik für Neurochirurgie, Universitätsklinikum Würzburg
  • Thomas Westermaier - Klinik für Neurochirurgie, Universitätsklinikum Würzburg

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. DocMO.08.05

doi: 10.3205/14dgnc039, urn:nbn:de:0183-14dgnc0394

Published: May 13, 2014

© 2014 Willner 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: Previous studies illustrated metabolic derangements and an accumulation of metabolic products following experimental subarachnoid hemorrhage (SAH), which may contribute to secondary brain damage. A possible cause could be deranged oxygen utilization due to enzymatic dysfunction in the aerobic glucose metabolism. This study was performed to investigate, if pyruvate dehydrogenase (PDH) – as a key enzyme to the TCA cycle – is affected in its activity regarding hemisphere and hippocampus, giving further evidence for a derangement of oxidative metabolism.

Method: Eighteen male Sprague-Dawley rats were randomly assigned to 2 groups (n = 9 per group): (1) SAH induced by the endovascular filament model or (2) sham-operated controls. Mean arterial blood pressure (MABP), intracranial pressure (ICP) and local cerebral blood flow (CBF), measured by laser-Doppler flowmetry over both hemispheres were measured from 30 minutes before until 3 hours after SAH. Then, animals were transcardially perfused with 4% paraformaldehyde and the brains were removed. The hemispheres and separated hippocampi got homogenized and the protein concentrations were determined by the Bradford method. Thereafter, the enzyme activity of PDH in hemispheres and hippocampi was measured by the PDH Enzyme Activity Microplate Assay Kit (MitoSciences).

Results: After induction of SAH, cerebral perfusion pressure (CPP) sharply decreased but returned to pre-hemorrhage values after 30 minutes. Local CBF immediately decreased to 20% of baseline over both hemispheres and slowly recovered to 65% of baseline at the end of the monitoring period. Results of enzyme activity analysis of PDH in hemispheres and hippocampi, using an enzyme-linked immunosorbant essay (ELISA), showed a significant reduction of the PDH activity in animals that were subjected to SAH compared to sham-operated animals 3 hours after SAH.

Conclusions: The results of this study demonstrate that PDH activity is reduced in the first hours after SAH, which may decisively contribute to a derangement of oxidative metabolism and lead to a persistent failure in oxygen utilization and, finally, secondary brain damage. Further investigations in the oxidative metabolic chain in experimental SAH are required to clarify this phenomenon and to find therapeutic options in the early phase of SAH.