Electrical stimulation of the cerebellar fastigial nucleus (FN) globally and profoundly increases cerebral blood flow via a cholinergic mechanism. In cerebral cortex, the vasodilation is unassociated with alterations in cerebral glucose utilization, a condition favoring protection against cerebral ischemia. We sought to determine whether FN stimulation would modify the size of the focal ischemic infarction resulting from occlusion of the middle cerebral artery (MCA). The MCA was occluded in anesthetized rats of the spontaneously hypertensive (SHR) or Sprague-Dawley (SD) strains with or without 1 h of electrical stimulation of the FN. Twenty-four hours later, rats were killed and the volume of the infarction established in thionin-stained sections. in SHRs, FN stimulation reduced by 40% the well-established cortical and partially subcortical infarctions elicited by occlusion of the MCA (from 186 +/- 35.2 to 113 +/- 47.1 mm3, mean +/- SD, n = 15; p less than 0.001). The zone of retrieval was anatomically constant, consisting of a rim of cortex dorsal and ventral to the infarction and medially within the thalamus and striatum corresponding to the penumbral zone described by others. The effect was comparable in rats of the SD strain having smaller infarctions. The effect of FN stimulation appears to be selective for the FN system in that it is not evoked by stimulation of the dentate nucleus and is blocked by systemic administration of atropine (1.0 mg/kg). We conclude that excitation of an intrinsic system in brain represented in the rostral FN has the capacity to reduce substantially an ischemic infarction.(ABSTRACT TRUNCATED AT 250 WORDS)