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 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.
Galea
E
E
Division of Neurobiology, Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021, USA. egalea@uic.educ
Golanov
E V
EV
Feinstein
D L
DL
Kobylarz
K A
KA
Glickstein
S B
SB
Reis
D J
DJ
D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology* / Q000517:prevention & control*; D002531:Cerebellum; D002536:Cerebral Arteries; D002552:Cerebral Ventricles; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000201:enzymology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D008297:Male; D008833:Microcirculation; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors
D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases