Scientific Reports (May 2024)

Ketamine-induced prevention of SD-associated late infarct progression in experimental ischemia

  • A. Zdunczyk,
  • L. Schumm,
  • S. O. A. Helgers,
  • M. Nieminen-Kelhä,
  • X. Bai,
  • S. Major,
  • J. P. Dreier,
  • N. Hecht,
  • Johannes Woitzik

DOI
https://doi.org/10.1038/s41598-024-59835-5
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 9

Abstract

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Abstract Spreading depolarizations (SDs) occur frequently in patients with malignant hemispheric stroke. In animal-based experiments, SDs have been shown to cause secondary neuronal damage and infarct expansion during the initial period of infarct progression. In contrast, the influence of SDs during the delayed period is not well characterized yet. Here, we analyzed the impact of SDs in the delayed phase after cerebral ischemia and the potential protective effect of ketamine. Focal ischemia was induced by distal occlusion of the left middle cerebral artery in C57BL6/J mice. 24 h after occlusion, SDs were measured using electrocorticography and laser-speckle imaging in three different study groups: control group without SD induction, SD induction with potassium chloride, and SD induction with potassium chloride and ketamine administration. Infarct progression was evaluated by sequential MRI scans. 24 h after occlusion, we observed spontaneous SDs with a rate of 0.33 SDs/hour which increased during potassium chloride application (3.37 SDs/hour). The analysis of the neurovascular coupling revealed prolonged hypoemic and hyperemic responses in this group. Stroke volume increased even 24 h after stroke onset in the SD-group. Ketamine treatment caused a lesser pronounced hypoemic response and prevented infarct growth in the delayed phase after experimental ischemia. Induction of SDs with potassium chloride was significantly associated with stroke progression even 24 h after stroke onset. Therefore, SD might be a significant contributor to delayed stroke progression. Ketamine might be a possible drug to prevent SD-induced delayed stroke progression.

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