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

Can TENG; Meiling YU; Guohui JIANG; Huiye FAN; Faxiang WANG

doi:10.16016/j.2097-0927.202312098

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

Neuroscience | 更新时间：2026-01-09

- Establishment and comparison of 2 mouse models of kainic acid induced epilepsy
- Journal of Army Medical University Vol. 46, Issue 7, Pages: 661-669(2024)
- 作者机构：
  
  1.400037 重庆，陆军军医大学(第三军医大学)第二附属医院神经内科
  2.637000 四川南充，川北医学院附属医院神经内科
  3.400037 重庆，陆军军医大学(第三军医大学)第二附属医院临床医学研究中心
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81971221);the General Program of Natural Science Foundation of Chongqing(cstc2021jcyj-msxm3511)
- DOI：10.16016/j.2097-0927.202312098
  CLC： R-334;R742.1
- Received：19 December 2023，
  
  Revised：2024-01-08，
  
  Published：15 April 2024
- 稿件说明：
移动端阅览
Can TENG, Meiling YU, Guohui JIANG, et al. Establishment and comparison of 2 mouse models of kainic acid induced epilepsy[J]. Journal of Army Medical University, 2024, 46(7): 661-669.
DOI：

Can TENG, Meiling YU, Guohui JIANG, et al. Establishment and comparison of 2 mouse models of kainic acid induced epilepsy[J]. Journal of Army Medical University, 2024, 46(7): 661-669. DOI： 10.16016/j.2097-0927.202312098.

摘要

目的

比较分析海人酸(kainic acid

KA)侧脑室(intracerebroventricular，ICV)注射和腹腔注射(intraperitoneal injections

IP)两种给药路径建立的颞叶癫痫小鼠模型早期的行为学和病理学差异。

方法

100只C57BL/6N野生型(wild type

WT)雄性小鼠(体质量为20~22 g)，按随机数字表法分为4组：ICV+ normal saline(NS)对照组(

=10)，ICV+KA模型组(

=40)，IP+NS对照组(

=10)，IP+KA模型组(

=40)。ICV+KA模型组使用600 nL的KA(0.5 mg/mL)进行侧脑室注射，IP+KA模型组按25 mg/kg剂量进行腹腔注射，对照组使用等量的生理盐水进行侧脑室

和腹腔注射。建立模型3 d后，进行行为学、分子生物学(Western blot)和神经病理损伤评估(FJB染色，TUNEL染色，免疫荧光染色)。

结果

两对照组无痫性发作，两模型组均出现痫性发作。IP+KA组与ICV+KA组死亡率分别为47.50%和65.00%，造模成功率分别为80.00%与60.00%。与IP+KA组比较，ICV+KA组小鼠模型成功率明显增高而死亡率明显减少。FJB染色和TUNEL染色结果显示，与IP+KA组比较，ICV+KA组海马的神经变性和凋亡改变程度变化更加明显(

0.05)。与IP+KA组比较，ICV+KA组海马凋亡蛋白表达差异也有统计学意义(

0.05)。免疫荧光结果显示，ICV+KA和IP+KA组海马和皮层的星形胶质细胞和小胶质细胞较对照组明显激活(

0.05)

但是ICV+KA组海马和皮层的胶质细胞激活程度均强于IP+KA组(

0.05)。ICV+KA组海马和皮层的GFAP和Iba-1蛋白表达均高于IP+KA组(

0.05)。

结论

两种KA制备方法均可制备出成功的癫痫模型。但ICV路径制备癫痫小鼠具有更高的成功率和更少的死亡率，并且神经病理损害程度和胶质细胞激活程度更加明显。

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(

=10)

ICV+KA model group(

=40)

IP+NS control group(

=10) and IP+KA model group (

=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 gro

ups. 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 (

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 (

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 (

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 (

0.05) and the activation levels in the ICV+KA group were higher than in the IP+KA model group (

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 (

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.

关键词

Keywords

references

FISHER R S, ACEVEDO C, ARZIMANOGLOU A, et al . ILAE Official Report: a practical clinical definition of epilepsy[J ] . Epilepsia, 2014, 55(4): 475-482. DOI: 10.1111/epi.12550.

THIJS R D, SURGES R, O'BRIEN T J, et al . Epilepsy in adults[J ] . Lancet, 2019, 393(10172): 689-701. DOI: 10.1016/S0140-6736(18)32596-0.

NELIGAN A, HAUSER W A, SANDER J W. The epidemiology of the epilepsies[J]. Handb Clin Neurol, 2012, 107: 113-133. DOI: 10.1016/B978-0-444-52898-8.00006-9.

KWAN P, BRODIE M J. Early identification of refractory epilepsy[J]. N Engl J Med, 2000, 342(5): 314-319. DOI: 10.1056/NEJM200002033420503.

KALILANI L, SUN X Z, PELGRIMS B, et al . The epidemiology of drug-resistant epilepsy: a systematic review and meta-analysis[J ] . Epilepsia, 2018, 59(1 2): 2179-2193. DOI: 10.1111/epi.14596.

WANG F X, YANG X L, MA Y S, et al . TRIF contributes to epileptogenesis in temporal lobe epilepsy during TLR4 activation[J ] . Brain Behav Immun, 2018, 67: 65-76. DOI: 10.1016/j.bbi.2017.07.157.

KEISER M S, CHEN Y H, DAVIDSON B L. Techniques for intracranial stereotaxic injections of adeno-associated viral vectors in adult mice[J]. Curr Protoc Mouse Biol, 2018, 8(4): e57. DOI: 10.1002/cpmo.57.

PIJET B, KONOPKA A, REJMAK E, et al . The matrix metalloproteinase inhibitor marimastat inhibits seizures in a model of kainic acid-induced status epilepticus[J ] . Sci Rep, 2020, 10: 21314. DOI: 10.1038/s41598-020-78341-y.

FERRARO T N, GOLDEN G T, SMITH G G, et al . Differential susceptibility to seizures induced by systemic kainic acid treatment in mature DBA/2J and C57BLl6J mice[J ] . Epilepsia, 1995, 36(3): 301-307. DOI: 10.1111/j.1528-1157.1995.tb00999.x.

BERGEY G K, MORRELL M J, MIZRAHI E M, et al . Long-term treatment with responsive brain stimulation in adults with refractory partial seizures[J ] . Neurology, 2015, 84(8): 810-817. D OI: 10.1212/wnl.0000000000001280.

DU K, HE M, ZHAO D Y, et al . Mechanism of cell death pathways in status epilepticus and related therapeutic agents[J ] . Biomed Pharmacother, 2022, 149: 112875. DOI: 10.1016/j.biopha.2022.112875.

SOKOLOVA T V, ZABRODSKAYA Y M, LITOVCHENKO A V, et al . Relationship between neuroglial apoptosis and neuroinflammation in the epileptic focus of the brain and in the blood of patients with drug-resistant epilepsy[J ] . Int J Mol Sci, 2022, 23(20): 12561. DOI: 10.3390/ijms232012561.

NABBOUT R, KUCHENBUCH M. Impact of predictive, preventive and precision medicine strategies in epilepsy[J]. Nat Rev Neurol, 2020, 16(12): 674-688. DOI: 10.1038/s41582-020-0409-4.

UPAGANLAWAR A B, WANKHEDE N L, KALE M B, et al . Interweaving epilepsy and neurodegeneration: vitamin E as a treatment approach[J ] . Biomed Pharmacother, 2021, 143: 112146. DOI: 10.1016/j.biopha.2021.112146.

SCHMUED L C, HOPKINS K J. Fluoro-Jade B: a high affinity fluorescent marker for the localization of neuronal degeneration[J]. Brain Res, 2000, 874(2): 123-130. DOI: 10.1016/S0006-8993(00)02513-0.

VEZZANI A, RAVIZZA T, BEDNER P, et al . Astrocytes in the initiation and progression of epilepsy[J ] . Nat Rev Neurol, 2022, 18(12): 707-722. DOI: 10.1038/s41582-022-00727-5.

YU C, DENG X J, XU D. Microglia in epilepsy[J]. Neurobiol Dis, 2023, 185: 106249. DOI: 10.1016/j.nbd.2023.106249.

PURNELL B S, ALVES M, BOISON D. Astrocyte-neuron circuits in epilepsy[J]. Neurobiol Dis, 2023, 179: 106058. DOI: 10.1016/j.nbd.2023.106058.

VEZZANI A, DI SAPIA R, KEBEDE V, et al . Neuroimmunology of status epilepticus[J ] . Epilepsy Behav, 2023, 140: 109095. DOI: 10.1016/j.yebeh.2023.109095.

CHEN Y, NAGIB M M, YASMEN N, et al . Neuroinflammatory mediators in acquired epilepsy: an update[J ] . Inflamm Res, 2023, 72(4): 683-701. DOI: 10.1007/s00011-023-01700-8.

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