Stimulation of cerebellar fastigial nucleus inhibits interleukin-1 beta-induced cerebrovascular inflammation

Electrical stimulation of the cerebellar fastigial nucleus (FN) in rat prot ects the brain against ischemia. We studied whether FN could reduce the cer ebrovascular inflammation as a mechanism of protection. FN or dentate nucle us (sham controls) was electrically stimulated for 1 h, and 72 h later rats were either injected with interleukin (IL)-1 beta into the striata or proc essed to analyze inflammatory responses in isolated brain microvessels. In striata, IL-1 beta induced a recruitment of leukocytes that was reduced by 50% by FN stimulation. In isolated microvessels, IL-1 beta induced the tran sient and dose-dependent upregulation of the mRNAs encoding for the inducib le nitric oxide synthase (NOS-2), intercellular adhesion molecule 1 (ICAM-1 ), and inhibitory kappa B-alpha (I kappa B-alpha), an inhibitor of nuclear factor-KB. FN stimulation decreased the upregulation of NOS-2 and ICAM-1 mR NAs, whereas it increased I kappa B-alpha mRNA expression. Dentate nucleus stimulation did not mimic the FN actions. These findings suggest that FN st imulation may render brain microvessels refractory to IL-1 beta by overprod uction of I kappa B-alpha and support the hypothesis that alteration of mic rovascular inflammation may contribute to the central neurogenic neuroprote ction elicited from the FN.