CEREBELLAR STIMULATION REDUCES INDUCIBLE NITRIC-OXIDE SYNTHASE EXPRESSION AND PROTECTS BRAIN FROM ISCHEMIA

A focal infarction produced by occlusion of the middle cerebral artery (MCAO) in spontaneously hypertensive rats induced expression of induc ible nitric oxide synthase (iNOS) mRNA, measured by competitive revers e transcription-polymerase chain reaction. The mRNA appeared simultane ously 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 synthas e (iNOS)-like immunoreactivity was present in the endothelium of cereb ral microvessels and in scattered cells, probably representing leukocy tes or activated microglia. Electrical stimulation of the cerebellar f astigial nucleus (FN) for 1 h, 48 h before MCAO, reduced infarct volum es by 45% by decreasing cellular death in the ischemic penumbra. It al so reduced by >90% the expression of iNOS mRNA and protein in the penu mbra, but not core, and decreased by 44% the iNOS enzyme activity. We conclude that excitation of neuronal networks represented in the cereb ellum elicits a conditioned central neurogenic neuroprotection associa ted with the downregulation of iNOS mRNA and protein. This neuroimmune interaction may, by blocking the expression of iNOS, contribute to ne uroprotection.