gms | German Medical Science

63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

13. - 16. Juni 2012, Leipzig

Reversal of cortical spreading ischemia induced vasoconstriction of isolated rat MCA by T-type Ca2+ channel inhibition

Meeting Abstract

  • U. Lindauer - Experimentelle Neurochirurgie und Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München
  • H. Baumgärtner - Experimentelle Neurochirurgie und Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München
  • M. Schreiber - Experimentelle Neurochirurgie und Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München
  • S. Pinkernell - Experimentelle Neurochirurgie und Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München
  • B. Meyer - Experimentelle Neurochirurgie und Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS). Leipzig, 13.-16.06.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. DocDO.01.01

DOI: 10.3205/12dgnc018, URN: urn:nbn:de:0183-12dgnc0185

Veröffentlicht: 4. Juni 2012

© 2012 Lindauer et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: During nitric oxide synthase (NOS) inhibition, cortical spreading depolarisation (CSD) can induce severe vasoconstriction (cortical spreading ischemia, CSI) [1]. CSI can be modeled in the isolated middle cerebral artery (MCA) by application of combined extraluminal ion changes according to changes of the extracellular milieu during CSI [2]. The CSI-associated vasoconstriction can be reverted to vasodilation by L-type Ca2+ channel inhibition with nimodipine. It has recently been shown that dihydropyridine-insensitive calcium currents contribute to cerebrovascular reactivity [3]. We therefore evaluated whether T-type Ca2+ channel inhibition is capable of reverting CSI-related vasoconstriction to vasodilation.

Methods: Rats were anesthetized and decapitated. The MCA was dissected, cannulated and pressurized. Vascular reactivity to CSI induced ion changes was tested under baseline conditions and under NOS inhibition, followed by L-type channel inhibition with nimodipine or by T-type channel inhibition by mibefradil during sustained NOS inhibition.

Results: In response to CSI cocktail the arteries significantly dilated from 75 ± 12 μm to 89 ± 17 μm. During NOS inhibition by L-NNA, CSI cocktail induced vasoconstriction from 54 ± 9 μm to 46 ± 7 μm, and application of the L-type channel antagonist nimodipine (10-7 M) as well as the T-type channel inhibitor mibefradil (10-8 M) reestablished vasodilation to CSI cocktail (nimodipine: baseline: 62 ± 15 μm, CSI cocktail: 72 ± 16 μm; mibefradil: baseline: 95 ± 12 μm, CSI cocktail: 113 ± 11 μm).

Conclusions: Compared with L-type channel inhibition, T-type channel inhibition is equally capable of reverting CSI-related vasoconstriction during NOS inhibition to vasodilation. In animal models of subarachnoid hemorrhage, expression of L-type channels has been shown to be reduced, whereas T-type channels are upregulated [4]. Because T-type channels have a larger role in smaller vessels [3], it has to be further evaluated whether combined block of T and L-type channels may represent an effective approach not only to reverse cerebral vasospasm of larger vessels but also CSD induced ischemic events within the microcirculation [5].


References

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