Neuroprotective electrical stimulation of cerebellar fastigial nucleus attenuates expression of periinfarction depolarizing waves (PIDs) and inhibitscortical spreading depression

Tn rat, electrical stimulation of the cerebellar fastigial nucleus (FN) for 1 h reduces the volume of focal ischemic infarctions produced by occluding the middle cerebral artery (MCAO), even 10 days later. The mechanism by wh ich this 'central neurogenic neuroprotection' salvages ischemic brain is no t known but does not result from changes in cerebral perfusion. MCAO also t riggers periodic periinfarction depolarizing waves (PIDs) in the ischemic p enumbra, the territory of salvage. These may contribute to neuronal death a nd promote infarct expansion. Conceivably, FN stimulation, which can otherw ise modify cortical excitability, may alter the development of PIDs. We inv estigated in anesthetized rats whether FN stimulation modifies PIDs express ion and, if so, the threshold for evoking cortical spreading depression (CS D), a process sharing characteristics with PIDs and an index of cortical ex citability. Stimulation of FN immediately or 72 h before MCAO decreased inf arction volumes by similar to 45% (p < 0.01), increased PLD latency > 10-fo ld, and decreased the number of PIDs by > 50% (p < 0.001). In normal rats, stimulation of FN increased the threshold current for eliciting CSD by 175% and slowed its propagation velocity by 35% (p < 0.01 for each) immediately , but not 72 h, after FN stimulation. We conclude: FN stimulation elicits l ong-lasting suppression of PIDs in parallel with neuroprotection. However, PIDs suppression over time is unlikely to result from a major increase in c ortical tolerance to depolarization and probably is not the principal mecha nism of salvage. (C) 1999 Elsevier Science B.V. All rights reserved.