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Chronic Trigeminal Nerve Stimulation Protects Against Seizures, Cognitive Impairments, Hippocampal Apoptosis, and Inflammatory Responses in Epileptic Rats

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Abstract

Trigeminal nerve stimulation (TNS) has recently been demonstrated effective in the treatment of epilepsy and mood disorders. Here, we aim to determine the effects of TNS on epileptogenesis, cognitive function, and the associated hippocampal apoptosis and inflammatory responses. Rats were injected with pilocarpine to produce status epilepticus (SE) and the following chronic epilepsy. After SE induction, TNS treatment was conducted for 4 consecutive weeks. A pilocarpine re-injection was then used to induce a seizure in the epileptic rats. The hippocampal neuronal apoptosis induced by seizure was assessed by TUNEL staining and inflammatory responses by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). The spontaneous recurrent seizure (SRS) number was counted through video monitoring, and the cognitive function assessed through Morris Water Maze (MWM) test. TNS treatment attenuated the SRS attacks and improved the cognitive impairment in epileptic rats. A pilocarpine re-injection resulted in less hippocampal neuronal apoptosis and reduced level of interleukin-1 beta (IL-1β), tumor necrosis factor-α (TNF-α), and microglial activation in epileptic rats with TNS treatment in comparison to the epileptic rats without TNS treatment. It is concluded that TNS treatment shortly after SE not only protected against the chronic spontaneous seizures but also improved cognitive impairments. These antiepileptic properties of TNS may be related to its attenuating effects on hippocampal apoptosis and pro-inflammatory responses.

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Acknowledgments

This work was supported by Natural Science grants to Y Wang (grant number: 81271444) from the National Natural Science Foundation of China and by the Key Scientific and Technological Project to Y Wang (grant number: 11010402168) from Anhui Science and Technology Department.

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Authors and Affiliations

  1. Department of Neurology, Epilepsy and Headache Group, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, 230022, China

    Qian-Qian Wang, Xian-Hong Wang, Jian Zuo, Hui-Yan He, Miao-Miao Tian, Lei Wang & Yu Wang

  2. Department of Neurology, Suzhou Municipal Hospital Affiliated to Anhui Medical University, Bianhe Middle Road 299, Suzhou, 234000, China

    Qian-Qian Wang

  3. Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, 310058, China

    Li-Jun Zhu

  4. Department of Neurology, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, 210029, China

    Xian-Hong Wang

  5. Department of Anesthesiology, The Second Division Korla Hospital of Xinjiang Production and Construction Corps, Jiaotong Road, Korla, Xinjiang, 841000, China

    Gui-Ling Liang

  6. Department of Neurology, The Second Division Korla Hospital of Xinjiang Production and Construction Corps, Jiaotong Road, Korla, Xinjiang, 841000, China

    Yu Wang

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  1. Qian-Qian Wang
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The protocol for this research project has been approved by the Ethics Committee of the Anhui Medical University within which the work was undertaken and that it conforms to the provisions of the Declaration of Helsinki.

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The authors declare that they have no competing interests.

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Qian-Qian Wang, Li-Jun Zhu, and Xian-Hong Wang contributed equally to this work

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Wang, QQ., Zhu, LJ., Wang, XH. et al. Chronic Trigeminal Nerve Stimulation Protects Against Seizures, Cognitive Impairments, Hippocampal Apoptosis, and Inflammatory Responses in Epileptic Rats. J Mol Neurosci 59, 78–89 (2016). https://doi.org/10.1007/s12031-016-0736-5

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