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The Effects of Amiloride on Seizure Activity, Cognitive Deficits and Seizure-Induced Neurogenesis in a Novel Rat Model of Febrile Seizures

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Abstract

Accumulating data suggest that sodium–hydrogen exchangers (NHEs) play a key role in modulating seizure activity by regulating neuronal pH in the brain. Amiloride, an inhibitor of NHEs, has been demonstrated to be effective in many seizure models, although its efficacy for prolonged febrile seizures (FS) remains unclear. In this study, we investigated whether amiloride could produce neuroprotective effects in a prolonged FS model in which FS were induced in rat pups at postnatal day 10 using a heated air approach. Amiloride was administered by intraperitoneal injection at three different doses (0.65, 1.3 and 2.6 mg/kg). Pretreatment with amiloride significantly delayed the onset of the first episode of limbic seizures, whereas posttreatment with amiloride decreased escape latency in the Morris water maze test compared to post-FS treatment with saline. Amiloride also inhibited seizure-induced aberrant neurogenesis. In conclusion, this study demonstrated the antiseizure activity of amiloride. In particular, posttreatment with amiloride resulted in cognitive improvement; this finding provides crucial evidence of the neuroprotective function of amiloride and of the therapeutic potential of amiloride in FS.

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Acknowledgments

This work was supported by grants from the National Science Foundation of China (Grant Numbers 81071051, 81271432). The funders played no role in study design, data collection and analysis, the decision to publish, or preparation of the manuscript.

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    Authors and Affiliations

    1. Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, People’s Republic of China

      Tang-Peng Ou-Yang, Yin-Xiu Ding, Feng Yang, Xiao-Long Sun & Wen Jiang

    2. Department of Neurology, Xi’an Central Hospital of Xi’an Jiaotong University College of Medicine, Xi’an, 710032, People’s Republic of China

      Ge-Min Zhu

    3. Department of Human Anatomy, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China

      Yin-Xiu Ding

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    1. Tang-Peng Ou-Yang
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    Correspondence to Wen Jiang.

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    Tang-Peng Ou-Yang and Ge-Min Zhu have contributed equally to this study.

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    Ou-Yang, TP., Zhu, GM., Ding, YX. et al. The Effects of Amiloride on Seizure Activity, Cognitive Deficits and Seizure-Induced Neurogenesis in a Novel Rat Model of Febrile Seizures. Neurochem Res 41, 933–942 (2016). https://doi.org/10.1007/s11064-015-1777-9

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