Stimulation of the subthalamic vasodilator area and fastigial nucleus independently protects the brain against focal ischemia

We investigated whether stimulation of the functionally discrete subthalami c region, subthalamic cerebrovasodilator area (SVA), which increases cerebr al blood flow (CBF) when excited, would, like stimulation of cerebellar fas tigial nucleus (FN), produce central neurogenic neuroprotection. A 1-h elec trical stimulation of SVA or FN reduced infarctions triggered by permanent occlusion of middle cerebral artery (MCA) by 48-55% in Sprague-Dawley rats and by 59% in Fisher rats. The salvaging effect of SVA stimulation, similar to FIN, was long lasting and reduced the volume of infarctions placed 72 h or 10 days later by 58 and 26%, respectively, in Fisher rats. Bilateral le sioning of FN neurons by the microinjection of ibotenic acid 5 days before SVA stimulation did not affect SVA-evoked neuroprotection. Bilateral lesion s of SVA neurons administered 5 days before FN stimulation had no effect on FN-induced neuroprotection but reversed the stimulus-locked increase in CB F accompanying FN stimulation. This study demonstrates that (1) excitation of neurons and/or fibers projecting through the SVA reduces ischemic infarc tions as substantially as excitation of FN neurons; (2) the effects are lon g-lasting and not attributable to increases in cerebral blood flow, changes in blood gases or brain temperature, or rat strain; (3) the neuroprotectiv e effects of SVA and FN stimulation are mutually independent and (4) FN-evo ked cerebrovasodilation is mediated by SVA neurons. The SVA and FN are part of a neuronal system in CNS, which is distributed and, when excited, acts to protect the brain from ischemic injury. (C) 2001 Published by Elsevier S cience B.V.