Effects of the nitric oxide donor, DEA/NO on cortical spreading depression

M. Wang, T. P. Obrenovitch*, J. Urenjak

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


Cortical spreading depression (CSD) is a transient disruption of local ionic homeostasis that may promote migraine attacks and the progression of stroke lesions. We reported previously that the local inhibition of nitric oxide (NO) synthesis with Nω-nitro-L-arginine methyl ester (L-NAME) delayed markedly the initiation of the recovery of ionic homeostasis from CSD. Here we describe a novel method for selective, controlled generation of exogenous NO in a functioning brain region. It is based on microdialysis perfusion of the NO donor, 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA/NO). As DEA/NO does not generate NO at alkaline pH, and as the brain has a strong acid-base buffering capacity, DEA/NO was perfused in a medium adjusted at alkaline (but unbuffered) pH. Without DEA/NO, such a microdialysis perfusion medium did not alter CSD. DEA/NO (1, 10 and 100 μM) had little effect on CSD by itself, but it reversed in a concentration-dependent manner the effects of NOS inhibition by 1 mM L-NAME. These data demonstrate that increased formation of endogenous NO associated with CSD is critical for subsequent, rapid recovery of cellular ionic homeostasis. In this case, the molecular targets for NO may be located either on brain cells to suppress mechanisms directly involved in CSD genesis, or on local blood vessels to couple flow to the increased energy demand associated with CSD.

Original languageEnglish
Pages (from-to)949-957
Number of pages9
Issue number7
Publication statusPublished - Jun 2003
Externally publishedYes


  • Cortical spreading depression
  • High extracellular potassium
  • Ionic homeostasis
  • Microdialysis
  • NO donor
  • Nitric oxide
  • Nitric oxide synthase
  • Nω-nitro-L-arginine methyl ester (L-NAME)


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