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

• Published in: Brain research Vol. 818; no. 2; pp. 304 - 315
• Main Authors: Golanov, Eugene V, Reis, Donald J
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 13-02-1999; Amsterdam Elsevier; New York, NY
• Subjects: Analysis of Variance; Animals; Biological and medical sciences; Cerebellar Nuclei - physiology; Cerebral focal ischemia; Cerebral Infarction - physiopathology; Cerebral Infarction - therapy; Cortical Spreading Depression; Electric Stimulation Therapy; Electroencephalography; Fastigial cerebellar nucleus; Male; Medical sciences; Membrane Potentials - physiology; Neurology; Neuroprotection; Periinfarct depolarization; Preconditioning; Rats; Rats, Sprague-Dawley; Spreading depression; Vascular diseases and vascular malformations of the nervous system; Fastigial cerebellar nucleus; Neuroprotection; Spreading depression; Preconditioning; Periinfarct depolarization; Cerebral focal ischemia; Cerebellum; Nervous system diseases; Rat; Electrical stimulus; Rodentia; Central nervous system; Cardiovascular disease; Cerebral disorder; Vascular disease; Depolarization; Vertebrata; Experimental disease; Mammalia; Fastigial nucleus; Ischemia; Animal; Central nervous system disease; Cerebrovascular disease; Brain (vertebrata)
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(98)01169-X

In 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 which this `central neurogenic neuroprotection' salvages ischemic brain is not known but does not result from changes in cerebral perfusion. MCAO also triggers periodic periinfarction depolarizing waves (PIDs) in the ischemic penumbra, the territory of salvage. These may contribute to neuronal death and promote infarct expansion. Conceivably, FN stimulation, which can otherwise modify cortical excitability, may alter the development of PIDs. We investigated in anesthetized rats whether FN stimulation modifies PIDs expression and, if so, the threshold for evoking cortical spreading depression (CSD), a process sharing characteristics with PIDs and an index of cortical excitability. Stimulation of FN immediately or 72 h before MCAO decreased infarction volumes by ∼45% (
p<0.01), increased PID latency >10-fold, 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 long-lasting suppression of PIDs in parallel with neuroprotection. However, PIDs suppression over time is unlikely to result from a major increase in cortical tolerance to depolarization and probably is not the principal mechanism of salvage.