title: Effectiveness of ketogenic diet in pentylenetetrazol-induced and kindling rats as well as its potential mechanisms.
abstract: The effects and mechanisms of ketogenic diets (KD) are unclear. In this study, we aimed to reveal electrographic and behavioral thresholds in responses to the KD in pentylenetetrazol (PTZ)-induced seizures, as well as its antiepileptogenic effects on PTZ-kindling rats. Additionally, we investigated the potential link between KD and expression levels of two cation chloride co-transporters: K(+)-Cl(-) co-transporter 2 (KCC2) and Na(+)-K(+)-Cl(-) co-transporter 1 (NKCC1). The KD group had significantly higher electrographic thresholds than the control (ND) group for the first spike-and-wave, subcontinuous spike-and-wave, high amplitude spike-and-wave, and polyspikes both in the cortex and hippocampus. Compared to the ND group, the KD group had higher behavioral thresholds for behavioral absence, first jerk, first overt myoclonia, and generalized seizures. In the PTZ-kindling model, KD not only prolonged the latency of myoclonic and clonic convulsions, but shortened clonic and generalized duration. In addition, KD rats had higher KCC2 protein expression before kindling, during myoclonic jerks, and GTCS compared with ND rats. There were no significant differences in NKCC1 protein levels between both groups following the four-week dietary intervention without PTZ exposure (before kindling). Moreover, KD inhibited the upregulation of NKCC1 expression induced by kindling in myoclonic jerks and GTCS. Therefore, our findings demonstrated that KD had antiepileptic features in elevating thresholds to most electrographic and behavioral seizure patterns in PTZ-induced rats, as well as delaying the progression and alleviating the severity of seizure in PTZ-kindling model. The antiepileptogenic effects of KD may be attributed to its regulatory properties on KCC2 and NKCC1 protein expression.
authors.affiliation: Epilepsy Center, Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Epilepsy Center, Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Epilepsy Center, Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Ding
authors.affiliation: Epilepsy Center, Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Liu
authors.affiliation: Epilepsy Center, Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Chun-Hong
authors.initials: CH
authors.lastname: Shen
authors.affiliation: Epilepsy Center, Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Jin
authors.affiliation: Epilepsy Center, Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Epilepsy Center, Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Epilepsy Center, Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: meipingd@163.com.
authors.forename: Mei-Ping
authors.initials: MP
authors.lastname: Ding
mesh_terms: D000818:Animals; D055423:Diet, Ketogenic; D007696:Kindling, Neurologic; D008297:Male; D010433:Pentylenetetrazole; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000178:diet therapy* / Q000209:etiology / Q000503:physiopathology; D064506:Solute Carrier Family 12, Member 2 / Q000378:metabolism; D027981:Symporters / Q000378:metabolism; D000096922:K Cl- Cotransporters
chemical_list: D010433:Pentylenetetrazole; D064506:Solute Carrier Family 12, Member 2; D027981:Symporters; D000096922:K Cl- Cotransporters
keywords: Electrographic threshold; K(+)–Cl(−) co-transporter 2; Ketogenic diet; Kindling; Na(+)–K(+)–Cl(−) co-transporter 1; Pentylenetetrazol