Seizure characteristics and hippocampus pathological alterations in two rat models of temporal lobe epilepsy induced by hippocampus and amygdala injection of kainic acid

Abstract

Objective To compare the behavioral manifestations, electroencephalogram(EEG) monitoring and hippocampal pathological changes in two rat epilepsy models induced by kainic acid (KA) injected into hippocampus and amygdala respectively. Methods Male adult Sprague-Dawley rats(n=24) were randomly divided into hippocampus model group (n=9), amygdala model group (n=9) and control group (n=6). Two epilepsy models were established by kainic acid (0.6 μg, 1.0 μg/μl) stereotactically injected into hippocampus CA3 region (hippocampus model) or amygdala (amygdala model). The status epilepticus (SE) of rats was observed by behavioral manifestations and EEG monitoring. Following successful modeling, those rats were randomly divided into 3 groups, including 1-day (acute phase), 7-day (latent phase) and 30-day (chronic phase) post SE groups (n=3 in each group). Rats in the control group were injected with an equal volume of saline in the hippocampal CA3 or amygdala. Immunohistochemistry was used for observing the pathological changes of neuron (NeuN), astrocyte (GFAP) and microglia (Iba1) in the rat hippocampus. Results Behavioral and EEG monitoring showed that rats from both models had typical seizure behaviors and EEG characteristics in the acute and chronic phases. However, there were different seize types and onset time between the 2 models in the acute phase. The hippocampus model group had partial seizures at 63.33±4.41 min post KA injection with intermittent generalized tonic-clonic seizures. Multi-phase spikes were recorded in acute phase. Amygdala model group had severe generalized tonic-clonic seizures at 28.67±3.48 min post KA injection, and the main cortical EEG form was sharp wave rhythm. Immunohistochemical staining revealed gradual hippocampal neuron death from acute to chronic phases in both models, which resulted in serious neuronal loss. Meanwhile, the aggravation of astrocyte proliferation and accumulation of microglia occurred in hippocampus in both models. Remarkably, compared with hippocampus model, the amygdala model in chronic phase had more neuronal loss in CA1 region (10.83±1.52 vs. 22.43±5.16, P<0.01) and CA4 region (12.87±2.13 vs. 25.81±4.60, P<0.05), more astrocyte proliferation in CA1 region (61.20±7.33 vs. 14.65±0.12, P<0.01) and CA4 region (76.73±5.40 vs. 43.01±1.35, P<0.01) as well as more widespread accumulation of microglia in CA1 region (13.70±3.88 vs. 1.08±0.01, P<0.01). Conclusions Our results have indicated that both rat epilepsy models simulated human temporal lobe epilepsy. The differences in the behavior, EEG performances and particularly pathological changes of hippocampus between two models should be taken into consideration in the future study. Key words: Epilepsy, temporal lobe; Hippocampus; Amygdala; Models, animal; Rats; Kainic acid