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- Title
Short-Term Plasticity of Hippocampal Neuropeptides and Neuronal Circuitry in Experimental Status Epilepticus.
- Authors
Wasterlain, Claude G.; Mazarati, Andrey M.; Naylor, David; Niquet, Jerome; Liu, Hantao; Suchomelova, Lucie; Baldwin, Roger; Katsumori, Hiroshi; Shirasaka, Yukiyoshi; Shin, Don; Sankar, Raman
- Abstract
Summary: Purpose: We used a model of self-staining status epilepticus (SSSE), induced by brief intermittent stimulation of the perforant path in unanesthetized rats, to study the mechanism of initiation and of maintenance of SSSE and the role of neuropeptides in those processes. Methods: The perforant path was stimulated intermittently for 7 min (ineffective stimulation) or 30 min (generating SSSE). Peptides and their agonists and antagonists were delivered either intraperitoneally, or directly into the hippocampus through a implanted cannula. Behavior and electroencephalogram (EEG) were recorded through a videotape-telemetry system with automatic spike and seizures detection programs, which were supplemented by manual review of the records to confirm the diagnosis. Immunocytochemistry and enzyme-linked immunosorbent assay followed published methods. Results: Initiation of SSSE was blocked by many agonists of inhibitory neurotransmitters or neuromodulators, and by many antagonists of excitatory synapses, and was facilitated by agents with the opposite action, suggesting the activation of a complex circuit with multiple potential entry points. Once SSSE was established, however, only N -methyl-d-aspartate (NMDA)-receptor ligands and a few neuropeptides had major effects on its maintenance. Galanin and dynorphin had powerful anticonvulsant roles in the maintenance phase of SSSE, whereas somatostatin and neuropeptide Y suppressed seizures only transiently. SSSE seemed to induce maladaptive changes in neuropeptides: it depleted the hippocampus of the galanin- and dynorphin-immunoreactive (IR) fibers, which normally function as endogenous anticonvulsants; whereas it induced overexpression of the proconvulsant neuropeptides substance P and neurokinin B; however, late in the course of SSSE, galanin-IR interneurons appeared in the dentate hilus. Conclusions: Initiation of SSSE seems to involve a circuit with many points of entry, and blockage of any point along this...
- Subjects
NEUROPEPTIDES; PHYSIOLOGICAL adaptation; SEA horses; EPILEPSY
- Publication
Epilepsia (Series 4), 2002, Vol 43, p20
- ISSN
0013-9580
- Publication type
Article
- DOI
10.1046/j.1528-1157.43.s.5.1.x