gms | German Medical Science

70. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Skandinavischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

12.05. - 15.05.2019, Würzburg

Characterisation of pyruvate dehydrogenase enzyme function following experimental SAH – potential target for neuroprotection?

Charakterisierung der Pyruvatdehydrogenasefunktion nach experimenteller SAB – potentielles Target zur Neuroprotektion?

Meeting Abstract

  • Nadine Lilla - Universitätsklinikum Würzburg, Neurochirurgische Klinik, Würzburg, Deutschland
  • presenting/speaker Alexandra Beez - Universitätsklinikum Würzburg, Neurochirurgische Klinik, Würzburg, Deutschland
  • Kastriot Alushi - Universitätsklinikum Würzburg, Neurochirurgische Klinik, Würzburg, Deutschland
  • Judith Weiland - Universitätsklinikum Würzburg, Neurochirurgische Klinik, Würzburg, Deutschland
  • Ralf-Ingo Ernestus - Universitätsklinikum Würzburg, Neurochirurgische Klinik, Würzburg, Deutschland
  • Thomas Westermaier - Universitätsklinikum Würzburg, Neurochirurgische Klinik, Würzburg, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 70. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Skandinavischen Gesellschaft für Neurochirurgie. Würzburg, 12.-15.05.2019. Düsseldorf: German Medical Science GMS Publishing House; 2019. DocV222

doi: 10.3205/19dgnc239, urn:nbn:de:0183-19dgnc2399

Veröffentlicht: 8. Mai 2019

© 2019 Lilla et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Objective: Previous studies illustrated metabolic derangements and an accumulation of metabolic products following experimental subarachnoid hemorrhage (SAH). This may contribute to secondary brain damage. A possible cause could be deranged oxygen utilization due to enzymatic dysfunction in the aerobic glucose metabolism. We therefore conducted this study to investigate if pyruvate dehydrogenase (PDH) – as a key enzyme to the TCA cycle – is affected in its activity during the course of the disease and might therefore act as a possible starting point for translational neuroprotective therapy.

Methods: 54 male Sprague-Dawley rats were randomly assigned to 1 of 2 groups (n=27): (1) SAH induced by the endovascular filament model or (2) sham-operated controls. Mean arterial blood pressure (MABP), intracranial pressure (ICP) and local CBF (laser-Doppler flowmetry) over both hemispheres were measured from 30 minutes before until 3 hours after SAH. Animals were then euthanized and the brains immediately stored in fluid nitrogen after 3 hours (n=9 SAH/9 sham), on day 3 (n=9 SAH/9 sham) and day 7 (n=9 SAH/9 sham). Right fontal hemispheres were homogenized and protein concentrations were determined by the Bradford method. Thereafter, the enzyme activity of PDH was measured via ELISA by the PDH Enzyme Activity Microplate Assay Kit (MitoSciences). Additional immunohistochemical staining 3 hours following experimental SAH, as well as on day 3 and day 7 after SAH/sham event was performed.

Results: PDH function was significantly reduced (p<0.05) after experimental SAH in contrast to sham operated controls 3 hours as well as on day 3 following experimental SAH in contrast to sham operated controls. On day 7 after experimental SAH, PDH function was significantly increased (p<0.001) in contrast to sham operated controls. Immunohistochemical staining underlined the ELISA results and showed less staining of PDH 3 hours and on day 3 following SAH as well as an increased staining of PDH on day 7 after experimental SAH.

Conclusion: PDH function is significantly reduced after experimental SAH already in the early phase and lasts at least until day 3 after experimental SAH. On day 7 after SAH there is a significant increase in PDH function, possibly due to upregulation. Therefore PDH might be a possible target for future neuroprotective therapy.