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The Journal of Neuroscience, May 15, 2001, 21(10):3593-3599

Status Epilepticus Causes Necrotic Damage in the Mediodorsal Nucleus of the Thalamus in Immature Rats

Hana Kubová¹, Rastislav Druga¹, Katarzyna Lukasiuk², Lucie Suchomelová¹, Renata Haugvicová¹, Iza Jirmanová¹, and Asla Pitkänen^{2, 3}

¹ Institute of Physiology, Academy of Sciences of the Czech Republic, Prague 4, CZ-142 20, Czech Republic, ² Epilepsy Research Laboratory, AI Virtanen Institute for Molecular Sciences, University of Kuopio, and ³ Department of Neurology, Kuopio University Hospital, FIN-70 211 Kuopio, Finland

Status epilepticus (StE) in immature rats causes long-term functional impairment. Whether this is associated with structural alterations remains controversial. The present study was designed to test the hypothesis that StE at an early age results in neuronal loss. StE was induced with lithium-pilocarpine in 12-d-old rats, and the presence of neuronal damage was investigated in the brain from 12 hr up to 1 week later using silver and Fluoro-Jade B staining techniques. Analysis of the sections indicated consistent neuronal damage in the central and lateral segments of the mediodorsal nucleus of the thalamus, which was confirmed using adjacent cresyl violet-stained preparations. The mechanism of thalamic damage (necrosis vs apoptosis) was investigated further using TUNEL, immunohistochemistry for caspase-3 and cytochrome c, and electron microscopy. Activated microglia were detected using OX-42 immunohistochemistry. The presence of silver and Fluoro-Jade B-positive degenerating neurons in the mediodorsal thalamic nucleus was associated with the appearance of OX-42-immunopositive activated microglia but not with the expression of markers of programmed cell death, caspase-3, or cytochrome c. Electron microscopy revealed necrosis of the ultrastructure of damaged neurons, providing further evidence that the mechanism of StE-induced damage in the mediodorsal thalamic nucleus at postnatal day 12 is necrosis rather than apoptosis. Finally, these data together with previously described functions of the medial and lateral segments of the mediodorsal thalamic nucleus suggest that some functions, such as adaptation to novelty, might become compromised after StE early in development.

Key words: apoptosis; development; microglia; necrosis; pilocarpine; TUNEL

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21103593-07$05.00/0

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