Neural Activities in Multiple Rat Brain Regions in Lithium-Pilocarpine-Induced Status Epilepticus Model

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-pilocarpineinduced 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.

In Vivo Microelectrode Arrays for Detecting Multi-Region Epileptic Activities in the Hippocampus in the Latent Period of Rat Model of Temporal Lobe Epilepsy

“…A recent study used tungsten wire electrodes to detect electroencephalogram (EEG) activities in multiple brain regions in the pilocarpine-induced status epilepticus model. The results showed robust EEG activities in the DG and CA3 areas, and relatively moderate responses in the CA1 area during status epilepticus [23]. The present study further discovered that on the cellular level, the neurons in the hilus and CA3 were more vulnerable to epileptic risk factors, and the interneurons in these areas were more injured by epileptic modeling.…”

Animal Models of Epilepsy: A Phenotype-oriented Review

“…Chemical kindling models are classified into subcutaneous, intraperitoneal, or intracerebral injections. Subcutaneous injection or intraperitoneal injection of kainic acid (KA), pilocarpine, or PTZ [ 80 - 83 ], or intracortical injection of KA have successfully established SE models [ 84 ]. The common pathological changes of intraamygdala or intrahippocampal injection of KA are neuronal cell loss, astrogliosis, mossy fiber sprouting, granule cell dispersion, and overexpression of the adenosine-metabolizing enzyme adenosine kinase [ 85 ].…”

“…Additionally, compared with the KA model, more serious neuronal damage is frequently found in the hippocampus, cortex, amygdala, hypothalamus, and endopiriform nucleus [ 33 ], and pilocarpine can induce SE rapidly at a low cost, although with higher mortality [ 86 ]. The PTZ model also presents dose variability and poor electric activity compared with the pilocarpine model [ 83 ].…”

The evolution of the pilocarpine animal model of status epilepticus

“…The lithium-pilocarpine model of SE is generally characterised by administration of lithium chloride (LiCl; 127 mg/kg), followed by pilocarpine administration (30 mg/kg) 18 h later ( Fan et al., 2020 ). Methylscopolamine (1 mg/kg in rats) is also given to the animals 30 min before pilocarpine administration to reduce any peripheral effects caused by pilocarpine, which unlike scopolamine, does not cross the blood brain barrier (BBB) ( Davis and Berger, 2013 ).…”