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.

The neocortex contains two neuron types, excitatory (glutamatergic) pyramidal cells and inhibitory nonpyramidal (GABAergic) cells. GABAergic, inhibitory interneurons are morphologically distinct from excitatory pyramidal cells and account for 20–25 % of all neocortical neurons. Recent studies discovered that besides morphological features, inhibitory interneurons are molecularly and physiologically heterogenous and differ significantly in arrangement and terminations of their axonal endings. In neocortical interneurons, GABA is also co-localized with calcium-binding proteins (parvalbumin, calbindin, calretinin), with neuropeptides and nitric oxide synthase. Axons of GABAergic neurons target distinct domains of pyramidal neurons. Double-bouquet, Martinotti and neurogliaform cells (CB-IR, CR-IR) target distal dendrites of pyramidal neurons and probably regulate the vertical integration of synaptic input along the dendritic tree of pyramids. Basket cells (PV-IR) innervate soma and proximal dendrites, and Chandelier cells (PV-IR) exhibit synaptic contacts on the axon initial segment of pyramidal neurons. GABAergic neocortical interneurons are interconnected by gap junctions. Most often coupling is bidirectional and occurs between interneurons of the same type. Cortical pyramidal neurons derive from the dorsal telencephalon while the majority of interneurons derive from the ganglionic eminences of the ventral telencephalon, and tangentially migrate into cortex. Adult mammalian neurogenesis is not restricted to the hippocampus, but a small number of the new neurons is also generated in the neocortex. New cortical neurons are GABAergic and co-express calbindin and calretinin. Quantitative analysis of selected areas of the neocortex (neuropsychiatric diseases, models of epilepsy, aging) demonstrate a decrease in density of PV-IR and CB-IR neurons but not CR-IR neurons.