Fastigial Stimulation Increases Ischemic Blood Flow and Reduces Brain Damage after Focal Ischemia

Abstract

Electrical stimulation of the cerebellar fastigial nucleus (FN) increases CBF and reduces brain damage after focal ischemia. We studied whether FN stimulation “protects” the brain from ischemic damage by increasing blood flow to the ischemic territory. Sprague–Dawley rats were anesthetized (halothane 1–3%) and artificially ventilated through a tracheal cannula inserted transorally. CBF was monitored by a laser-Doppler probe placed over the convexity at a site corresponding to the area spared from infarction by FN stimulation. Arterial pressure (AP), blood gases, and body temperature were controlled, and the electroencephalogram (EEG) was monitored. The stem of the middle cerebral artery (MCA) was occluded. After occlusion, the FN was stimulated for 60 min (100 μA; 50 Hz; 1 s on–1 s off) while AP was maintained at 97 ± 11 mm Hg (mean ± SD) by controlled hemorrhage. Rats were then allowed to recover, and infarct volume was determined 24 h later in thioninstained sections. In unstimulated rats (n = 7), proximal MCA occlusion reduced CBF and the amplitude of the EEG. One day later, these rats had infarcts involving neocortex and striatum. FN stimulation after MCA occlusion (n = 12) enhanced CBF and EEG recovery [61 ± 34 and 73 ± 43%, respectively at 60 min; p < 0.05 vs. unstimulated group; analysis of variance (ANOVA)] and reduced the volume of the cortical infarct by 48% (p < 0.05). In contrast, hypercapnia (Pco₂ = 64 ± 4; n = 7) did not affect CBF and EEG recovery or infarct volume (p > 0.05). Thus, FN stimulation, unlike hypercapnia, increases CBF to the ischemic cortex, improves recovery of electrical activity, and reduces tissue damage after MCA occlusion. These findings support the hypothesis that FN stimulation reduces ischemic damage by enhancing collateral flow to the ischemic territory.