Skip to main content
Article thumbnail
Location of Repository

Nitric oxide formation during cortical spreading depression is critical for rapid subsequent recovery of ionic homeostasis

By Jutta A. Urenjak, Tihomir P. Obrenovitch and M. Wang


NoCortical spreading depression (CSD) is a temporary disruption of local ionic homeostasis that propagates slowly across the cerebral cortex. Cortical spreading depression promotes lesion progression in experimental stroke, and may contribute to the initiation of migraine attacks. The purpose of this study was to investigate the roles of the marked increase of nitric oxide (NO) formation that occurs with CSD. Microdialysis electrodes were implanted in the cortex of anesthetized rats to perform the following operations within the same region: (1) elicitation of CSD by perfusion of high K+ medium; (2) recording of CSD elicitation; (3) application of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME); and (4) recording of dialysate pH changes. The primary effect of L-NAME (0.3 to 3.0 mmol/L in the perfusion medium) was a marked widening of individual CSD wave, resulting essentially from a delayed initiation of the repolarization phase. This change was due to NO synthase inhibition because it was not observed with the inactive isomer D-NAME, and was reversed by L-arginine. This effect did not appear to be linked to the suppression of a sustained, NO-mediated vascular change associated with the superposition of NO synthase inhibition on high levels of extracellular K+. The delayed initiation of repolarization with local NO synthase inhibition may reflect the suppression of NO-mediated negative feedback mechanisms acting on neuronal or glial processes involved in CSD genesis. However, the possible abrogation of a very brief, NO-mediated vascular change associated with the early phase of CSD cannot be ruled out

Topics: Spreading depression, Nitric oxide, Nitric oxide synthase, L-NAME, Migraine, Sroke, N-methyl-d-aspartate
Year: 2009
OAI identifier:
Provided by: Bradford Scholars

Suggested articles


  1. (1992). A simple biological way to screen dopaminergic agonists. Metab Brain Dis 7:211–221 Desvignes doi
  2. (1995). Arginine-nitric oxide pathway and cerebrovascular regulation in cortical spreading depression.
  3. (1994). Extracellular glucose concentration in mammalian brain: continuous monitoring of changes during increased neuronal activity and upon limitation in oxygen supply in normo-, hypo-, and hyperglycemic animals.
  4. (1992). General anesthetics inhibit the responses induced by glutamate receptor agonists in the mouse cortex. Neurosci Lett 146:21–24 Chen KC, doi
  5. (1996). Metab Rev 7:297–323 Obrenovitch TP, Zilkha E
  6. (1998). Nitric oxide does not mediate cerebral blood flow changes during cortical spreading depression in the anaesthetised rat. Neurosci Lett 250:115–118 doi
  7. (2001). Nitric oxide synthases: structure, function and inhibition. doi
  8. (1998). Pharmacological modulation of the refractory period of retinal spreading depression. doi
  9. (1974). The mechanisms and applications of Leao’s spreading depression of electroencephalographic activity.
  10. (1996). Use-dependent loss of acetylcholine- and bradykinin-mediated vasodilation after nitric oxide synthase inhibition: evidence for preformed stores of nitric oxide-containing factors in vascular endothelial cells. Hypertension 28:354–360 Dawson VL, doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.