Intrinsic neurons of fastigial nucleus mediate neurogenic neuroprotection against excitotoxic and ischemic neuronal injury in rat

Electrical stimulation of the cerebellar fastigial nucleus (FN) elevates re gional cerebral blood flow (rCBF) and arterial pressure (AP) and provides l ong-lasting protection against focal and global ischemic infarctions. We in vestigated which neuronal element in FN, perikarya or axons, mediates this central neurogenic neuroprotection and whether it also protects against exc itotoxicity. In anesthetized rats, the FN was stimulated for 1 hr, and ibot enic acid (IBO) was microinjected unilaterally into the striatum. In unstim ulated controls, the excitotoxic lesions averaged similar to 40 mm(3). Stim ulation of FN, but not dentate nucleus (DN), significantly reduced lesion v olumes up to 80% when IBO was injected 15 min, 72 hr, or 10 d, but not 30 d , thereafter. In other rats, intrinsic neurons of FN or DN were destroyed b y pretreatment with IBO. Five days later, the FN was stimulated, and 72 hr later, IBO was microinjected into the striatum. Lesions of FN, but not DN, abolished neuroprotection but not the elevations of rCBF and AP elicited fr om FN stimulation. Excitotoxic lesions of FN, but not DN, also abolished th e 37% reduction in focal ischemic infarctions produced by middle cerebral a rtery occlusion. Excitation of intrinsic FN neurons provides long-lasting, substantial, and reversible protection of central neurons from excitotoxici ty, as well as focal ischemia, whereas axons in the nucleus, probably colla terals of ramified brainstem neurons, mediate the elevations in rCBF, which do not contribute to neuroprotection. Long-lived protection against a rang e of injuries is an unrecognized function of FN neurons transmitted over pa thways distinct from those regulating rCBF.