Spreading depolarizations increase delayed brain injury in a rat model of subarachnoid hemorrhage

Arend M. Hamming, Marieke J H Wermer, S. Umesh Rudrapatna, Christian Lanier, Hine J A Van Os, Walter M. Van Den Bergh, Michel D. Ferrari, Annette Van Der Toorn, Arn M J M Van Den Maagdenberg, Ann M. Stowe, Rick M. Dijkhuizen

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15 Scopus citations

Abstract

Spreading depolarizations may contribute to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage, but the effect of spreading depolarizations on brain lesion progression after subarachnoid hemorrhage has not yet been assessed directly. Therefore, we tested the hypothesis that artificially induced spreading depolarizations increase brain tissue damage in a rat model of subarachnoid hemorrhage. Subarachnoid hemorrhage was induced by endovascular puncture of the right internal carotid bifurcation. After one day, brain tissue damage was measured with T 2 -weighted MRI, followed by application of 1 M KCl (SD group, N = 16) or saline (no-SD group, N = 16) to the right cortex. Cortical laser-Doppler flowmetry was performed to record spreading depolarizations. MRI was repeated on day 3, after which brains were extracted for assessment of subarachnoid hemorrhage severity and histological damage. 5.0 ± 2.7 spreading depolarizations were recorded in the SD group. Subarachnoid hemorrhage severity and mortality were similar between the SD and no-SD groups. Subarachnoid hemorrhage-induced brain lesions expanded between days 1 and 3. This lesion growth was larger in the SD group (241 ± 233mm3) than in the no-SD group (29 ± 54mm3) (p = 0.001). We conclude that induction of spreading depolarizations significantly advances lesion growth after experimental subarachnoid hemorrhage. Our study underscores the pathophysiological consequence of spreading depolarizations in the development of delayed cerebral tissue injury after subarachnoid hemorrhage.

Original languageEnglish (US)
Pages (from-to)1224-1231
Number of pages8
JournalJournal of Cerebral Blood Flow and Metabolism
Volume36
Issue number7
DOIs
StatePublished - Jul 1 2016

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Keywords

  • animal models
  • brain imaging
  • magnetic resonance
  • spreading depression
  • Subarachnoid hemorrhage

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Hamming, A. M., Wermer, M. J. H., Umesh Rudrapatna, S., Lanier, C., Van Os, H. J. A., Van Den Bergh, W. M., Ferrari, M. D., Van Der Toorn, A., Van Den Maagdenberg, A. M. J. M., Stowe, A. M., & Dijkhuizen, R. M. (2016). Spreading depolarizations increase delayed brain injury in a rat model of subarachnoid hemorrhage. Journal of Cerebral Blood Flow and Metabolism, 36(7), 1224-1231. https://doi.org/10.1177/0271678X15619189