Abstract
To clarify the different regional brain electroencephalogram (EEG) activities and biochemical responses in seizure and epilepsy models, we assessed the EEG and c-Fos immunolabeling characteristics in a lithium-pilocarpine-induced status epilepticus (SE) model and pentylenetetrazol (PTZ)-induced seizure model. The regional brain activities were evaluated by EEG and c-Fos immunolabeling. ZnT3 immunostaining was performed to observe hippocampal mossy fiber sprouting (MFS) within 7 days after the induction of SE in the lithium-pilocarpine model. The EEG recordings showed distinctive features of activation in different brain areas. With the aggravation of the behavioral manifestations of the seizures, the frequency and amplitude of the discharges on EEG gradually increased. SE was eventually induced and sustained. The labeling of c-Fos was enhanced in the cortex and hippocampal CA1, CA3, and dentate gyrus (DG); however, compared to the PTZ-induced seizure model, c-Fos staining could only be observed in the striatum and thalamus in the lithium-pilocarpine-induced epilepsy model. In each brain region, prominent c-Fos labeling was observed 2 h and 4 h after the induction of SE or seizures and diminished at 24 h. During the lithium-pilocarpine-induced chronic epilepsy phase after SE induction, MFS was observed 7 days after SE and was accompanied by the dynamic evolution of epileptic EEG activities. These findings validated the lithium-pilocarpine-induced SE model as an epilepsy model with a specific spatial-temporal profile of neural activation. The EEG characteristics and c-Fos expression patterns differ from those presented in a previous study using a PTZ-induced seizure model. Hippocampal mossy fiber spouting might be associated with spontaneous seizures during the chronic phase and can be detected at least within 1 week by ZnT3 staining after stimulation.
Highlights
Epilepsy is a complex neurological disease with a variety of manifestations, etiologies and pathogenesis
Temporal lobe epilepsy (TLE) is the most common type of partial epilepsy (Téllez-Zenteno and Hernández-Ronquillo, 2012), which is characterized by recurrent spontaneous convulsive seizures that are associated with significant neuron loss and morphological changes affecting mainly mesial temporal structures such as the amygdala and hippocampal formation (French et al, 1993; Engel, 1996; Bernasconi et al, 2003)
The results showed that the main structures recruited in the Lithium-Pilocarpine-induced Status epilepticus (SE) model included the Cortex, the hippocampal formation (CA1, Cornu Ammonis area 3 (CA3) and dentate gyrus (DG)) and the striatum, which exhibited significant c-Fos immunolabeling
Summary
Epilepsy is a complex neurological disease with a variety of manifestations, etiologies and pathogenesis. The epilepsy model induced by pilocarpine could reproduce the main clinical and pathophysiological characteristics of human TLE, i.e., hippocampal sclerosis, mossy fiber sprouting (MFS), cell dispersion in the dentate gyrus (DG), and gliosis (Leite et al, 1990; Curia et al, 2008). This model could reproduce the severe neuronal damage in the mesial structures of the brain (Kandratavicius et al, 2014)
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