Stimulation of cerebellar fastigial nucleus inhibits interleukin-1beta-induced cerebrovascular inflammation.
Electrical stimulation of the cerebellar fastigial nucleus (FN) in rat protects the brain against ischemia. We studied whether FN could reduce the cerebrovascular inflammation as a mechanism of protection. FN or dentate nucleus (sham controls) was electrically stimulated for 1 h, and 72 h later rats were either injected with interleukin (IL)-1beta into the striata or processed to analyze inflammatory responses in isolated brain microvessels. In striata, IL-1beta induced a recruitment of leukocytes that was reduced by 50% by FN stimulation. In isolated microvessels, IL-1beta induced the transient and dose-dependent upregulation of the mRNAs encoding for the inducible nitric oxide synthase (NOS-2), intercellular adhesion molecule 1 (ICAM-1), and inhibitory kappaB-alpha (IkappaB-alpha), an inhibitor of nuclear factor-kappaB. FN stimulation decreased the upregulation of NOS-2 and ICAM-1 mRNAs, whereas it increased IkappaB-alpha mRNA expression. Dentate nucleus stimulation did not mimic the FN actions. These findings suggest that FN stimulation may render brain microvessels refractory to IL-1beta by overproduction of IkappaB-alpha and support the hypothesis that alteration of microvascular inflammation may contribute to the central neurogenic neuroprotection elicited from the FN.
Galea
E
E
Division of Neurobiology, Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021, USA.
Glickstein
S B
SB
Feinstein
D L
DL
Golanov
E V
EV
Reis
D J
DJ
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000502:physiology; D002529:Cerebellar Nuclei / Q000502:physiology*; D002561:Cerebrovascular Disorders / Q000517:prevention & control*; D004268:DNA-Binding Proteins / Q000235:genetics; D004558:Electric Stimulation; D020672:I-kappa B Proteins; D066298:In Vitro Techniques; D007249:Inflammation / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D008297:Male; D008833:Microcirculation / Q000502:physiology; D008845:Microinjections; D019001:Nitric Oxide Synthase / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D007375:Interleukin-1; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D019001:Nitric Oxide Synthase