Establishment and comparison of 2 mouse models of kainic acid induced epilepsy

Abstract

Objective To investigate and analyze the behavioral and pathological differences in early-stage mouse models of epilepsy established by 2 different administration routes for kainic acid (KA), intracerebroventricular (ICV) injection and intraperitoneal (IP) injection. Methods A total of 100 male C57BL/6N wild-type (WT) mice (20~22 g) were randomly divided into ICV+ normal saline (NS)control group(n=10), ICV+KA model group(n=40), IP+NS control group(n=10) and IP+KA model group (n=40). The ICV+KA model group was given 600 nL of KA (0.5 mg/mL) via ICV injection, and the IP+KA model group was injected with different dose of KA (25 mg/kg). Two control groups were administered equal volumes of NS via corresponding routes. After 3 d of modeling, the evaluation of behavioristics, molecular biology (including Western blotting), and neuropathological assessments (including FJB staining, TUNEL staining and immunofluorescence staining) were performed. Results No epileptic seizures were observed in both 2 control groups, while exhibited seizures were observed in both model groups. The mortality rates of the IP+KA group and the ICV+KA group were 47.50% and 65.00% respectively, while the success rates of modeling were 80.00% and 60.00% respectively. Compared with the IP+KA group, the ICV+KA group showed a significant increase in success rate and a significant reduction in mortality rate. FJB and TUNEL staining results showed that, compared with the IP+KA group, the severity of neurodegeneration and apoptotic changes in the hippocampus of the ICV+KA group were more significant (P < 0.05). Compared with the IP+KA group, there was also a significant difference in the expression of apoptotic proteins in the hippocampus of the ICV+KA group (P < 0.05). Immunofluorescence results showed that the astrocytes and microglia in the hippocampus and cortex of the ICV+KA and IP+KA groups were significantly activated compared with the control groups (P < 0.05), but the activation of glial cells in the hippocampus and cortex of the ICV+KA group was stronger than that of the IP+KA model group (P < 0.05) and the activation levels in the ICV+KA group were higher than in the IP+KA model group (P < 0.01). Moreover, expression levels of GFAP and Iba-1 proteins in the hippocampus and cortex were higher in the ICV+KA group than the IP+KA group (P < 0.05). Conclusion Two routes of KA administration are effective in construct epilepsy models. The mice with ICV administration route show a higher success rate and lower mortality rate, and more significant neuropathological damage and glial cell activation.

Keywords

• temporal lobe epilepsy
• kainic acid
• intracerebroventricular injection
• intraperitoneal injection
• pathological differences