Ischemia triggered by spreading neuronal activation is induced by endothelin‐1 and hemoglobin in the subarachnoid space

Ischemia triggered by spreading neuronal activation is induced by endothelin‐1 and hemoglobin... Delayed cerebral vasospasm has a major impact on the outcome of subarachnoid hemorrhage. Two important candidates to cause the arterial spasm are the red blood cell product oxyhemoglobin and the vasoconstrictor endothelin‐1, although oxyhemoglobin alone is not sufficient to induce cerebral ischemia and endothelin‐1 leads to ischemia only at relatively high concentrations. In this study, we demonstrated that the combination of oxyhemoglobin and endothelin‐1 triggered spreading neuronal activation in rat cortex in vivo. In contrast with the expected transient increase of regional cerebral blood flow during spreading depression, however, cerebral blood flow decreased profoundly and was long‐lasting, paralleled by delayed repolarization of the steady (direct current) potential. These changes are characteristic of cortical spreading ischemia. Replacing oxyhemoglobin for the nitric oxide synthase inhibitor Nω‐nitro‐L‐arginine mimicked these effects, implicating nitric oxide scavenging functions of oxyhemoglobin. Furthermore, the effect of endothelin‐1 was related to a reduction of Na+‐/K+‐ATPase activity rather than solely to its vasoconstrictive properties. In conclusion, the threshold concentration of endothelin‐1 that induces cerebral ischemia is profoundly reduced via a complex interaction between the neuronal/astroglial network and the cortical microcirculation if nitric oxide availability declines. The results may have implications for the understanding of subarachnoid hemorrhage–related cortical lesions. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Neurology Wiley

Ischemia triggered by spreading neuronal activation is induced by endothelin‐1 and hemoglobin in the subarachnoid space

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Publisher
Wiley
Copyright
Copyright © 2003 American Neurological Association
ISSN
0364-5134
eISSN
1531-8249
DOI
10.1002/ana.10723
Publisher site
See Article on Publisher Site

Abstract

Delayed cerebral vasospasm has a major impact on the outcome of subarachnoid hemorrhage. Two important candidates to cause the arterial spasm are the red blood cell product oxyhemoglobin and the vasoconstrictor endothelin‐1, although oxyhemoglobin alone is not sufficient to induce cerebral ischemia and endothelin‐1 leads to ischemia only at relatively high concentrations. In this study, we demonstrated that the combination of oxyhemoglobin and endothelin‐1 triggered spreading neuronal activation in rat cortex in vivo. In contrast with the expected transient increase of regional cerebral blood flow during spreading depression, however, cerebral blood flow decreased profoundly and was long‐lasting, paralleled by delayed repolarization of the steady (direct current) potential. These changes are characteristic of cortical spreading ischemia. Replacing oxyhemoglobin for the nitric oxide synthase inhibitor Nω‐nitro‐L‐arginine mimicked these effects, implicating nitric oxide scavenging functions of oxyhemoglobin. Furthermore, the effect of endothelin‐1 was related to a reduction of Na+‐/K+‐ATPase activity rather than solely to its vasoconstrictive properties. In conclusion, the threshold concentration of endothelin‐1 that induces cerebral ischemia is profoundly reduced via a complex interaction between the neuronal/astroglial network and the cortical microcirculation if nitric oxide availability declines. The results may have implications for the understanding of subarachnoid hemorrhage–related cortical lesions.

Journal

Annals of NeurologyWiley

Published: Nov 1, 2003

References

  • Focal laminar cortical MR signal abnormalities after subarachnoid hemorrhage
    Dreier, Dreier; Sakowitz, Sakowitz; Harder, Harder
  • Ischaemia triggered by spreading neuronal activation is inhibited by vasodilators in rats
    Dreier, Dreier; Petzold, Petzold; Tille, Tille
  • Isozymes of the Na‐K‐ATPase: heterogeneity in structure, diversity in function
    Blanco, Blanco; Mercer, Mercer
  • Acute and chronic effects of potassium and noradrenaline on Na+, K+‐ATPase activity in cultured mouse neurons and astrocytes
    Hajek, Hajek; Subbarao, Subbarao; Hertz, Hertz
  • Spreading depression, sustained potential shifts, and metabolic activity of cerebral cortex of cats
    Rosenthal, Rosenthal; Somjen, Somjen
  • Factors inducing endothelium‐dependent relaxation in the guinea‐pig basilar artery as estimated from the actions of haemoglobin
    Nishiye, Nishiye; Nakao, Nakao; Itoh, Itoh; Kuriyama, Kuriyama
  • Nitric oxide in the potassium‐induced response of the rat middle cerebral artery: a possible permissive role
    Golding, Golding; Steenberg, Steenberg; Johnson, Johnson; Bryan, Bryan
  • Hemoglobin increases endothelin‐1 in endothelial cells by decreasing nitric oxide
    Lin, Lin; MacDonald, MacDonald; Marton, Marton

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