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

Abstract

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)-1β into the striata or processed to analyze inflammatory responses in isolated brain microvessels. In striata, IL-1β induced a recruitment of leukocytes that was reduced by 50% by FN stimulation. In isolated microvessels, IL-1β 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 κB-α (IκB-α), an inhibitor of nuclear factor-κB, FN stimulation decreased the upregulation of NOS-2 and ICAM-1 mRNAs, whereas it increased IκB-α mRNA expression. Dentate nucleus stimulation did not mimic the FN actions. These findings suggest that FN stimulation may render brain microvessels refractory to IL-1β by overproduction of IκB-α and support the hypothesis that alteration of microvascular inflammation may contribute to the central neurogenic neuroprotection elicited from the FN.