Cerebellar stimulation reduces inducible nitric oxide synthase expression and protects brain from ischemia

Elena Galea, Eugene V. Golanov, Douglas L. Feinstein, Keith A. Kobylarz, Sara B. Glickstein, Donald J. Reis

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

A focal infarction produced by occlusion of the middle cerebral artery (MCAO) in spontaneously hypertensive rats induced expression of inducible nitric oxide synthase (iNOS) mRNA, measured by competitive reverse transcription-polymerase chain reaction. The mRNA appeared simultaneously in the ischemic core and penumbra at 8 h, peaked between 14 and 24 h, and disappeared by 48 h. At 24 h, inducible nitric oxide synthase (iNOS)-like immunoreactivity was present in the endothelium of cerebral microvessels and in scattered cells, probably representing leukocytes or activated microglia. Electrical stimulation of the cerebellar fastigial nucleus (FN) for 1 h, 48 h before MCAO, reduced infarct volumes by 45% by decreasing cellular death in the ischemic penumbra. It also reduced by >90% the expression of iNOS mRNA and protein in the penumbra, but not core, and decreased by 44% the iNOS enzyme activity. We conclude that excitation of neuronal networks represented in the cerebellum elicits a conditioned central neurogenic neuroprotection associated with the downregulation of iNOS mRNA and protein. This neuroimmune interaction may, by blocking the expression of iNOS, contribute to neuroprotection.

Original languageEnglish (US)
Pages (from-to)H2035-H2045
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume274
Issue number6 43-6
DOIs
StatePublished - 1998

Keywords

  • Brain endothelium
  • Brain macrophages
  • Brain microvessels
  • Cerebellum

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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