Region‐specific plasticity in the epileptic rat brain: A hippocampal and extrahippocampal analysis

Summary Purpose:  Recent evidence suggests that aberrant neuro/gliogenesis and/or inflammation play critical roles in epileptogenesis. Although the plastic and inflammatory changes have been described in the postseizure hippocampus, little data is available concerning extrahippocampal regions, notably in the piriform and entorhinal cortices, amygdala, and parts of the thalamus. In this study, we examined histological changes in whole epileptic rat brain, with respect to cell death, cell genesis, and inflammation. Methods and Results:  Experimental status epilepticus (SE) was induced using a lithium-pilocarpine injection. Neuronal death was evident in the amygdala, piriform, and entorhinal cortices, as well as the subfields of hippocampus. Microglial activation was observed in more extended limbic areas, such as, the hippocampus, entorhinal, perirhinal and piriform cortices, amygdala, thalamus, and hypothalamus, and a robust increase of cell genesis was noted in these damaged areas. The majority of newly generated cells in extrahippocampal areas proliferated in situ, and differentiated mainly into astrocytes or oligodendrocytes. In addition, stromal cell-derived factor-1α was found to be induced in close temporal and anatomical association with seizure-induced plasticity. Discussion:  These findings indicate that neuronal death, inflammation, and cell genesis are substantially associated throughout the entire brain and that they may influence the epileptogenic process and clinical manifestations.