title: Chronic Trigeminal Nerve Stimulation Protects Against Seizures, Cognitive Impairments, Hippocampal Apoptosis, and Inflammatory Responses in Epileptic Rats.
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.
authors.affiliation: Department of Neurology, Epilepsy and Headache Group, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, 230022, China.|Department of Neurology, Suzhou Municipal Hospital Affiliated to Anhui Medical University, Bianhe Middle Road 299, Suzhou, 234000, China.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Epilepsy and Headache Group, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, 230022, China.|Department of Neurology, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Xian-Hong
authors.initials: XH
authors.lastname: Wang
authors.affiliation: Department of Neurology, Epilepsy and Headache Group, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, 230022, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zuo
authors.affiliation: Department of Neurology, Epilepsy and Headache Group, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, 230022, China.
authors.forename: Hui-Yan
authors.initials: HY
authors.lastname: He
authors.affiliation: Department of Neurology, Epilepsy and Headache Group, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, 230022, China.
authors.forename: Miao-Miao
authors.initials: MM
authors.lastname: Tian
authors.affiliation: Department of Neurology, Epilepsy and Headache Group, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, 230022, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, The Second Division Korla Hospital of Xinjiang Production and Construction Corps, Jiaotong Road, Korla, Xinjiang, 841000, China.
authors.forename: Gui-Ling
authors.initials: GL
authors.lastname: Liang
authors.affiliation: Department of Neurology, Epilepsy and Headache Group, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, 230022, China. yw4d@hotmail.com.|Department of Neurology, The Second Division Korla Hospital of Xinjiang Production and Construction Corps, Jiaotong Road, Korla, Xinjiang, 841000, China. yw4d@hotmail.com.
authors.forename: Yu
authors.identifier: http://orcid.org/0000-0002-9454-9699
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D060825:Cognitive Dysfunction / Q000628:therapy*; D004827:Epilepsy / Q000628:therapy*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000628:therapy*; D004561:Transcutaneous Electric Nerve Stimulation; D014276:Trigeminal Nerve / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha
keywords: Apoptosis; Cognitive function; Epileptogenesis; Interleukin-1β; Microglia; Trigeminal nerve stimulation; Tumor necrosis factor-α