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Endothelin-1(1–31) Induces Spreading Depolarization in Rats

  • Conference paper
Early Brain Injury or Cerebral Vasospasm

Part of the book series: Acta Neurochirurgica Supplements ((NEUROCHIRURGICA,volume 110/1))

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Abstract

Background: The vasoconstrictor endothelin-1(1–21) (ET-1) seems to induce cerebral vasospasm after aneurismal subarachnoid hemorrhage (aSAH). Moreover, ET-1 causes spreading depolarization (SD) via vasoconstriction/ischemia. ET-1(1–31) is an alternate metabolic intermediate in the generation of ET-1. Our aim was to investigate whether endothelin-1(1–31) causes SD in a similar fashion to ET-1.

Method: Increasing concentrations of either ET-1, ET-1(1–31) or vehicle were brain topically applied in 29 rats. Each concentration was superfused for one hour while regional cerebral blood flow (rCBF) and direct current electrocorticogram (DC-ECoG) were recorded.

Findings: In response to the highest concentration of 10-−6M, all animals of both ET groups developed typical SD. At concentrations below 10-−6M only ET-1 induced SD (n = 14 of 19 rats). Thus, the efficacy of ET-1(1–31) to induce SD was significantly lower (P < 0.001, two-tailed Fisher’s Exact Test).

Conclusions: Our findings suggest that ET-1(1–31) less potently induces SD compared to ET-1 which implicates that it is a less potent vasoconstrictor. Speculatively, it could be interesting to shift the metabolic pathway towards the alternate intermediate ET-1(1–31) after aSAH as an alternative strategy to ETA receptor inhibition. This could decrease ET-induced vasoconstriction and SD generation while a potentially beneficial basal ETA receptor activation is maintained.

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Acknowledgement

Supported by grants of the Deutsche Forschungsgemeinschaft (DFG DR 323/2–2), the Bundesministerium für Bildung und Forschung (Center for Stroke Research Berlin, 01 EO 0801) and the Kompetenznetz Schlaganfall to Dr. Dreier.

Conflict of interest statement We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Experimental Neurology, Charité University Medicine Berlin, Berlin, Germany

    D. Jorks, S. Major, A. I. Oliveira-Ferreira & J. P. Dreier

  2. Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany

    D. Jorks, S. Major, A. I. Oliveira-Ferreira & J. P. Dreier

  3. Department of Neurology, Charité University Medicine Berlin, Berlin, Germany

    S. Major & J. P. Dreier

  4. Service de neuropsychologie et neuroréhabilitation, Hôpital Nestlé CHUV, Lausanne, Switzerland

    J. Kleeberg

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Correspondence to J. P. Dreier .

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Editors and Affiliations

  1. Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Gaotanyan 30, Chongqing, 400038, China

    H.-J. Steiger  & Hua Feng  & 

  2. Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China

    Ying Mao

  3. Departments of Physiology and Neurosurgery, Loma Linda University School of Medicine, Risley Hall, Room 223, 92354, Loma Linda, California, USA

    John H. Zhang

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Jorks, D., Major, S., Oliveira-Ferreira, A.I., Kleeberg, J., Dreier, J.P. (2011). Endothelin-1(1–31) Induces Spreading Depolarization in Rats. In: Feng, H., Mao, Y., Zhang, J.H. (eds) Early Brain Injury or Cerebral Vasospasm. Acta Neurochirurgica Supplements, vol 110/1. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0353-1_20

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  • DOI: https://doi.org/10.1007/978-3-7091-0353-1_20

  • Publisher Name: Springer, Vienna

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