Prolonged Induction of Neuronal NOS Expression and Activity Following Cortical Spreading Depression (SD): Implications for SD- and NO-Mediated Neuroprotection

Prolonged Induction of Neuronal NOS Expression and Activity Following Cortical Spreading... Cortical spreading depression (CSD) is associated with various short- and long-term physiological and neurochemical changes and has been shown to confer an increased susceptibility to accompanying ischemic injury or provide protection against a subsequent experimental ischemia. Nitric oxide is involved in the processes of ischemic injury and under certain conditions mediates cellular protection. To investigate the possibility that CSD-induced alterations in nitric oxide synthase (NOS) expression and activity occur and might be associated with the time-dependent enhancement or prevention by CSD of ischemic damage, this study examined the spatiotemporal changes in nNOS expression and activity in cerebral cortex following CSD. Anesthetized rats had unilateral CSD induced by a 10-min topical application of KCl and were killed at various times thereafter. CSD increased both nNOS mRNA and protein levels throughout layers II–III of cortex. nNOS mRNA in the affected neocortex was significantly increased by 30–90% at 2, 7, and 14 days ( P ≤ 0.05) compared with contralateral levels, but was not significantly above control values at 1–6 h, 1 day, and 28 days after CSD induction. Levels of ( 3 H)- l - N G -nitroarginine binding to NOS were increased by 40–170% 7, 14, and 28 days ( P ≤ 0.01) after CSD in a similar, but delayed, profile to nNOS mRNA. Levels of nNOS-immunoreactivity were also increased in both neurons and astrocytes of ipsilateral cortex 7 and 14 days after CSD—confirmed by double-immunofluorescence localization. Ex vivo NOS activity in layers I–III of ipsilateral cortex was also increased by 30–50% ( P ≤ 0.01) at 7 and 14 days after CSD, times coincident with reported maximal ischemic protection. These results demonstrate that nNOS is up-regulated by cellular depolarization/depression occurring during CSD, or by resultant stimuli and suggest that “CSD-conditioned” cortex may be capable of producing appropriate levels of NO to mediate or contribute to protective/adaptive responses to subsequent physical ischemic injury. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Experimental Neurology Elsevier

Prolonged Induction of Neuronal NOS Expression and Activity Following Cortical Spreading Depression (SD): Implications for SD- and NO-Mediated Neuroprotection

Experimental Neurology, Volume 160 (2) – Dec 1, 1999

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Publisher
Elsevier
Copyright
Copyright © 1999 Academic Press
ISSN
0014-4886
DOI
10.1006/exnr.1999.7218
Publisher site
See Article on Publisher Site

Abstract

Cortical spreading depression (CSD) is associated with various short- and long-term physiological and neurochemical changes and has been shown to confer an increased susceptibility to accompanying ischemic injury or provide protection against a subsequent experimental ischemia. Nitric oxide is involved in the processes of ischemic injury and under certain conditions mediates cellular protection. To investigate the possibility that CSD-induced alterations in nitric oxide synthase (NOS) expression and activity occur and might be associated with the time-dependent enhancement or prevention by CSD of ischemic damage, this study examined the spatiotemporal changes in nNOS expression and activity in cerebral cortex following CSD. Anesthetized rats had unilateral CSD induced by a 10-min topical application of KCl and were killed at various times thereafter. CSD increased both nNOS mRNA and protein levels throughout layers II–III of cortex. nNOS mRNA in the affected neocortex was significantly increased by 30–90% at 2, 7, and 14 days ( P ≤ 0.05) compared with contralateral levels, but was not significantly above control values at 1–6 h, 1 day, and 28 days after CSD induction. Levels of ( 3 H)- l - N G -nitroarginine binding to NOS were increased by 40–170% 7, 14, and 28 days ( P ≤ 0.01) after CSD in a similar, but delayed, profile to nNOS mRNA. Levels of nNOS-immunoreactivity were also increased in both neurons and astrocytes of ipsilateral cortex 7 and 14 days after CSD—confirmed by double-immunofluorescence localization. Ex vivo NOS activity in layers I–III of ipsilateral cortex was also increased by 30–50% ( P ≤ 0.01) at 7 and 14 days after CSD, times coincident with reported maximal ischemic protection. These results demonstrate that nNOS is up-regulated by cellular depolarization/depression occurring during CSD, or by resultant stimuli and suggest that “CSD-conditioned” cortex may be capable of producing appropriate levels of NO to mediate or contribute to protective/adaptive responses to subsequent physical ischemic injury.

Journal

Experimental NeurologyElsevier

Published: Dec 1, 1999

References

  • Nitric oxide synthases: Properties and catalytic mechanisms
    Griffith, O.W.; Stuehr, D.J.
  • Autoradiographic distribution of ( 3 H) l -N G -nitro-arginine binding in rat brain
    Kidd, E.J.; Nichel, A.D.; Humphrey, P.P.
  • Light-scattering changes accompanying spreading depression in isolated retina
    Martins-Ferreira, H.; de Oliveira Castro, G.
  • l -Arginine decreases infarct size caused by middle cerebral arterial occlusion in SHR
    Morikawa, E.; Huang, Z.; Moskowitz, M.A.
  • Food and water deprivation modulate nitric oxide synthase (NOS) activity and gene expression in rat hypothalamic neurons: Correlation with neurosecretory activity
    O'Shea, R.D.; Gundlach, A.L.
  • Nitric oxide does not mediate cerebral blood flow changes during cortical spreading depression in the anaesthetised rat
    Read, S.J.; Parsons, A.A.
  • The dynamics of nitric oxide release measured directly and in real time following repeated waves of cortical spreading depression in the anaesthetised cat
    Read, S.J.; Smith, M.I.; Hunter, A.J.; Parsons, A.A.
  • Nitric oxide regulates excitatory amino acid release in a biphasic manner in freely moving rats
    Segieth, J.; Getting, S.J.; Biggs, C.S.; Whitton, P.S.
  • Differential increases in chromogranins, but not synapsin I, in cortical neurons following spreading depression: Implications for functional roles and transmitter peptide release
    Shen, P.-J.; Gundlach, A.L.
  • Effects of nitric oxide on the retinal spreading depression
    Ulmer, H.J.; Fernandes de Lima, V.M.; Hanke, W.
  • Infarct tolerance against temporary focal ischemia following spreading depression in rat brain
    Yanamoto, H.; Hashimoto, N.; Nagata, I.; Kikuchi, H.
  • Transient expression of neuronal nitric oxide synthase by neurons of the submucous plexus of the mouse small intestine
    Young, H.M.; Ciampoli, D.

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