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Gastrodin Reduces the Severity of Status Epilepticus in the Rat Pilocarpine Model of Temporal Lobe Epilepsy by Inhibiting Nav1.6 Sodium Currents

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Abstract

Temporal lobe epilepsy (TLE) is one of the most refractory types of adult epilepsy, and treatment options remain unsatisfactory. Gastrodin (GAS), a phenolic glucoside used in Chinese herbal medicine and derived from Gastrodia elata Blume, has been shown to have remarkable anticonvulsant effects on various models of epilepsy in vivo. However, the mechanisms of GAS as an anticonvulsant drug remain to be established. By utilizing a combination of behavioral surveys, immunofluorescence and electrophysiological recordings, the present study characterized the anticonvulsant effect of GAS in a pilocarpine-induced status epilepticus (SE) rat model of TLE and explored the underlying cellular mechanisms. We found that GAS pretreatment effectively reduced the severity of SE in the acute phase of TLE. Moreover, GAS protected medial entorhinal cortex (mEC) layer III neurons from neuronal death and terminated the SE-induced bursting discharge of mEC layer II neurons from SE-experienced rats. Furthermore, the current study revealed that GAS prevented the pilocarpine-induced enhancement of Nav1.6 currents (persistent (INaP) and resurgent (INaR) currents), which were reported to play a critical role in the generation of bursting spikes. Consistent with this result, GAS treatment reversed the expression of Nav1.6 protein in SE-experienced EC neurons. These results suggest that the inhibition of Nav1.6 sodium currents may be the underlying mechanism of GAS’s anticonvulsant properties.

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Acknowledgments

This work was supported by grants from the National Natural Foundation of China (31671106), the Scientific Foundation of Chongqing (CSTC2015JCYJA10108).

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Authors and Affiliations

  1. Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Gaotanyan Street 30, Chongqing, 400038, China

    Hui Shao, Yang Yang, Ai-ping Qi, Pian Hong, Guang-xi Zhu & Zhi-ru Zhu

  2. Department of Physiology, Third Military Medical University, Chongqing, China

    Hui Shao & Zhi-ru Zhu

  3. The Fifth Camp of Cadet Brigade, Third Military Medical University, Chongqing, China

    Hui Shao & Xin-yu Cao

  4. Department of Chemistry, Faculty of Pharmacy, Third Military Medical University, Chongqing, China

    Wei-gang Ji

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  1. Hui Shao
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Shao, H., Yang, Y., Qi, Ap. et al. Gastrodin Reduces the Severity of Status Epilepticus in the Rat Pilocarpine Model of Temporal Lobe Epilepsy by Inhibiting Nav1.6 Sodium Currents. Neurochem Res 42, 360–374 (2017). https://doi.org/10.1007/s11064-016-2079-6

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