Status epilepticus causes necrotic damage in the mediodorsal nucleus of the thalamus in immature rats

Status epilepticus (StE) in immature rats causes long- term functional impa irment. Whether this is associated with structural alterations remains cont roversial. The present study was designed to test the hypothesis that StE a t an early age results in neuronal loss. StE was induced with lithium- pilo carpine in 12-d-old rats, and the presence of neuronal damage was investiga ted 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 neuro nal damage in the central and lateral segments of the mediodorsal nucleus o f the thalamus, which was confirmed using adjacent cresyl violet- stained p reparations. The mechanism of thalamic damage (necrosis vs apoptosis) was i nvestigated further using TUNEL, immunohistochemistry for caspase- 3 and cy tochrome c, and electron microscopy. Activated microglia were detected usin g OX-42 immunohistochemistry. The presence of silver and Fluoro- Jade B- po sitive degenerating neurons in the mediodorsal thalamic nucleus was associa ted with the appearance of OX-42-immunopositive activated microglia but not with the expression of markers of programmed cell death, caspase- 3, or cy tochrome c. Electron microscopy revealed necrosis of the ultrastructure of damaged neurons, providing further evidence that the mechanism of StE- indu ced damage in the mediodorsal thalamic nucleus at postnatal day 12 is necro sis rather than apoptosis. Finally, these data together with previously des cribed functions of the medial and lateral segments of the mediodorsal thal amic nucleus suggest that some functions, such as adaptation to novelty, mi ght become compromised after StE early in development.