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Jung-Ah Lim, Jangsup Moon, Tae-Joon Kim, Jin-Sun Jun, Byeongsu Park, Jung-Ick Byun, Jun-Sang Sunwoo, Kyung-Il Park, Soon-Tae Lee, Keun-Hwa Jung, Ki-Young Jung, Manho Kim, Daejong Jeon, Kon Chu, Sang Kun Lee
Seizure clustering is a common and significant phenomenon in patients with epilepsy. The clustering of spontaneous recurrent seizures (SRSs) in animal models of epilepsy, including mouse pilocarpine models, has been reported. However, most studies have analyzed seizures for a short duration after the induction of status epilepticus (SE). In this study, we investigated the detailed characteristics of seizure clustering in the chronic stage of a mouse pilocarpine-induced epilepsy model for an extended duration by continuous 24/7 video-EEG monitoring...
2018: PloS One
Tianlin Wang, Xin Zhou, Yan Bai, Lan Zhang, Lin Li, Chunfu Wu
Uridine is a potential endogenous neuromodulator studied for several decades for its antiepileptic effect, but the results were controversial. One remarkable feature of uridine is its regulatory action on the dopaminergic pathways. In this study, the changes in uridine and dopamine (DA) release were examined in the mouse corpus striatum after pilocarpine (PC) intraperitoneal injection. Then, the effect of uridine pre-treatment on DA release and expression of dopamine receptor (DR) was determined. The results revealed an increased uridine release initially, followed by a downward trend after an injection of 400-mg/kg PC...
March 16, 2018: Brain Research
Ji-Eun Kim, Kyung-Ok Cho
Temporal lobe epilepsy (TLE) is a common neurological disorder in adulthood. For translational studies of chronic epilepsy, pilocarpine-induced status epilepticus (SE) is frequently selected to recapitulate spontaneous recurrent seizures (SRS). Here we present a protocol of SE induction by intraperitoneal (i.p.) injection of pilocarpine and monitoring of chronic recurring seizures in live animals using a wireless telemetry video and electroencephalogram (EEG) system. We demonstrated notable behavioral changes that need attention after pilocarpine injection and their correlation with hippocampal neuronal loss at 7 days and 6 weeks post-pilocarpine...
February 27, 2018: Journal of Visualized Experiments: JoVE
Rui-Fang Wang, Guo-Fang Xue, Christian Hölscher, Miao-Jing Tian, Peng Feng, Ji-Ying Zheng, Dong-Fang Li
Glucagon-like peptide-1(GLP-1) is a growth factor that has neuroprotective and anti-inflammatory properties. The protease resistant GLP-1 analogue liraglutide has been shown to be neuroprotective in previous studies in animal models of Alzheimer's disease or Parkinson's disease. Status epilepticus (SE) is a complex disorder, involving many underlying pathological processes, including excitotoxic and chronic inflammatory events. The present pilot study aims to investigate whether liraglutide alleviates the chronic inflammation response and mitochondrial stress induced by SE in the lithium-pilocarpine animal model...
March 9, 2018: Epilepsy Research
Emily C Mahoney, Andrew Zeng, Wilson Yu, Mackenzie Rowe, Siddhartha Sahai, Paul J Feustel, Adolfo Ramirez-Zamora, Julie G Pilitsis, Damian S Shin
Approximately 30% of individuals with epilepsy are refractory to antiepileptic drugs and currently approved neuromodulatory approaches fall short of providing seizure freedom for many individuals with limited utility for generalized seizures. Here, we expand on previous findings and investigate whether ventral pallidum deep brain stimulation (VP-DBS) can be efficacious for various acute seizure phenotypes. For rats administered pilocarpine, we found that VP-DBS (50 Hz) decreased generalized stage 4/5 seizure median frequency from 9 to 6 and total duration from 1667 to 264 s even after generalized seizures emerged...
March 9, 2018: Epilepsy Research
Aruna Vashishta, Lukasz P Slomnicki, Maciej Pietrzak, Scott C Smith, Murali Kolikonda, Shivani P Naik, Rosanna Parlato, Michal Hetman
Ribosome biogenesis, including the RNA polymerase 1 (Pol1)-mediated transcription of rRNA, is regulated by the pro-epileptogenic mTOR pathway. Therefore, hippocampal Pol1 activity was examined in mouse models of epilepsy including kainic acid- and pilocarpine-induced status epilepticus (SE) as well as a single seizure in response to pentylenetetrazole (PTZ). Elevated 47S pre-rRNA levels were present acutely after induction of SE suggesting activation of Pol1. Conversely, after a single seizure, 47S pre-rRNA was transiently downregulated with increased levels of unprocessed 18S rRNA precursors in the cornu Ammonis (CA) region...
March 15, 2018: Molecular Neurobiology
Kamila Cagliari Zenki, Eduardo Kalinine, Eduardo R Zimmer, Thainá Garbino Dos Santos, Ben Hur Marins Mussulini, Luis Valmor Cruz Portela, Diogo Lösch de Oliveira
Several works have demonstrated that status epilepticus (SE) induced-neurodegeneration appears to involve an overactivation of N-methyl-D-aspartate receptors and treatment with high-affinity NMDAR antagonists is neuroprotective against this brain damage. However, these compounds display undesirable side effects for patients since they block physiological NMDA receptor dependent-activity. In this context, memantine (MN), a well tolerable low-affinity NMDAR channel blocker, will be a promising alternative, since it does not compromise the physiological role of NMDA receptors on synaptic transmission...
March 12, 2018: Neurotoxicology
Kun Zhu, Bo Yuan, Ming Hu, Cheng-Jun Li, Jie-Hua Xu, Gai-Feng Feng, Yong Liu, Jian-Xin Liu
Pilocarpine-induced acute seizures strongly induce aberrant hippocampal neurogenesis, characterized by increased proliferation of neural progenitors and abnormal integrations of newly generated granule cells - hilar ectopic granule cells (EGCs), mossy fibre sprouting (MFS), and hilar basal dendrites (HBDs), which may disturb hippocampal neuronal circuits and thus contribute to cognitive impairment in temporal lobe epilepsy (TLE) patients and animal models. Previous studies via ablating hippocampal neurogenesis after acute seizures produced inconsistent results regarding the development of long-term cognitive impairment...
March 3, 2018: Epilepsy Research
Mayara Lütchemeyer de Freitas, Clarissa Vasconcelos de Oliveira, Fernanda Kulinski Mello, Vinícius Rafael Funck, Michele Rechia Fighera, Luiz Fernando Freire Royes, Ana Flávia Furian, James W Larrick, Mauro Schneider Oliveira
Na+ , K+ -ATPase is an important regulator of brain excitability. Accordingly, compelling evidence indicates that impairment of Na+ , K+ -ATPase activity contributes to seizure activity in epileptic mice and human with epilepsy. In addition, this enzyme is crucial for plasma membrane transport of water, glucose and several chemical mediators, including glutamate, the major excitatory transmitter in the mammalian brain. Since glucose hypometabolism and increased glutamate levels occur in clinical and experimental epilepsy, we aimed the present study to investigate whether activation of Na+ ,K+ -ATPase activity with specific antibody (DRRSAb) would improve glucose uptake and glutamate release in pilocarpine-treated mice...
March 6, 2018: Neuroscience
Mahdi Haghighatafshar, Mehrnaz Ghaedian, Zahra Etemadi, Seyed M Entezarmahdi, Tahereh Ghaedian
OBJECTIVE: Although different methods have been suggested on reducing salivary gland radiation after radioiodine administration, an effective preventive or therapeutic measure is still up for debate. The aim of this study was to evaluate the effect of pilocarpine, as a sialagogue drug on the radioiodine content of the salivary gland, and radioiodine-induced symptoms of salivary gland dysfunction. PATIENTS AND METHODS: Patients who were referred for radioiodine therapy were randomized into pilocarpine and placebo groups...
March 6, 2018: Nuclear Medicine Communications
Tian-Tian Liu, Yi Li, Yi Shu, Bo Xiao, Li Feng
Ephrin‑B3 is important in the regulation of cell proliferation, differentiation and migration via cell‑cell contact, and can activate the reelin pathway during brain development. However, the effect of ephrin‑B3 on hippocampal neurogenesis and the reelin pathway in epilepsy remains to be fully elucidated. In the present study, the expression of ephrin‑B3 in pilocarpine‑induced status epilepticus (SE) rats was investigated. SYBR Green‑based reverse transcription‑quantitative polymerase chain reaction analysis, immunohistochemical labeling and western blot analysis were used to detect the gene and protein expression levels of ephrin‑B3 and reelin pathway proteins...
March 7, 2018: International Journal of Molecular Medicine
Machiko Watanabe, Chisato Yamada, Yoshinori Komagata, Hirotoshi Kikuchi, Hiroyuki Hosono, Fumio Itagaki
Background: Patients with Sjögren's syndrome (SS) typically present clinically with xerostomia (dry mouth) because of progressive damage to the exocrine glands. We developed a new, low-dose pilocarpine/sodium alginate (LPA) solution with pilocarpine hydrochloride to inhibit systemic adverse effects by administering via the oral mucosa. The purpose of this study was to assess its stability, safety, and efficacy. Methods: The pilocarpine concentration in an LPA liquid formulation was measured 3, 7, 14, and 28 days after preparation to assess its stability...
2018: Journal of Pharmaceutical Health Care and Sciences
Adriana Fernanda K Vizuete, Fernanda Hansen, Elisa Negri, Marina Concli Leite, Diogo Losch de Oliveira, Carlos-Alberto Gonçalves
BACKGROUND: Temporal lobe epilepsy (TLE) is the most common form of partial epilepsy and is accompanied, in one third of cases, by resistance to antiepileptic drugs (AED). Most AED target neuronal activity modulated by ionic channels, and the steroid sensitivity of these channels has supported the use of corticosteroids as adjunctives to AED. Assuming the importance of astrocytes in neuronal activity, we investigated inflammatory and astroglial markers in the hippocampus, a key structure affected in TLE and in the Li-pilocarpine model of epilepsy...
March 5, 2018: Journal of Neuroinflammation
J Papinska, H Bagavant, G B Gmyrek, M Sroka, S Tummala, K A Fitzgerald, U S Deshmukh
Sjögren syndrome (SS), a chronic autoimmune disorder causing dry mouth, adversely affects the overall oral health in patients. Activation of innate immune responses and excessive production of type I interferons (IFNs) play a critical role in the pathogenesis of this disorder. Recognition of nucleic acids by cytosolic nucleic acid sensors is a major trigger for the induction of type I IFNs. Upon activation, cytosolic DNA sensors can interact with the stimulator of interferon genes (STING) protein, and activation of STING causes increased expression of type I IFNs...
March 1, 2018: Journal of Dental Research
Yian Huang, Yuwen Zhang, Shuzhen Kong, Kai Zang, Shize Jiang, Li Wan, Lulan Chen, Guoxiang Wang, Min Jiang, Xin Wang, Jie Hu, Yun Wang
G protein-gated inwardly rectifying potassium (GIRK) channels are important inhibitory regulators of neuronal excitability in central nervous system, and the impairment of GIRK channel function has been reported to be associated with the susceptibility of epilepsy. However, the dynamics of GIRK channels in the pathogenesis of epilepsy are still unclear. In this study, our results showed that cyclothiazide, a potent convulsant, dose dependently increased the epileptiform bursting activities and suppressed the baclofen induced GIRK currents...
February 27, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ya-Bo Feng, You-Ting Lin, Yu-Xiang Han, Yue-Jiu Pang, Jing-Jing Xu, Yuan Xue, Hong Yao
This study aimed to study the protective effect of (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC), a selective metabotropic glutamate receptor agonist, against hippocampal neuronal apoptosis induced by seizures in a rat model of pilocarpine-induced epilepsy. The Morris water maze test was used to assess the spatial memory abilities of epileptic rats with or without 2R,4R-APDC treatment. TUNEL assay was performed to examine neuronal apoptosis in hippocampus. Western blot was conducted to evaluate changes in the levels of caspase-3 and caspase-9 in hippocampus...
March 1, 2018: Neurochemical Research
Jinghui Zhang, Nana Qiao, Xiufang Ding, Jiwen Wang
Excitotoxicity and neuronal death following epilepsy involve α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). It forms a protein complex with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and co-internalizes upon activation of AMPA receptors after epilepsy. Disruption of the GluA2/GAPDH complex with an interfering peptide, TAT-GluA2NT1-3-2, protects cells against AMPAR-mediated excitotoxicity, which have been identified in in-vitro and in-vivo models of brain ischemia. We postulated that disruption of the GluA2/GAPDH interaction with the TAT-GluA2NT1-3-2 peptide would also protect against AMPAR-induced neuronal injury in an in-vivo model of status epilepticus (SE)...
March 21, 2018: Neuroreport
Soheila Samiee, Maxime Lévesque, Massimo Avoli, Sylvain Baillet
Polyrhythmic coupling of oscillatory components in electrophysiological signals results from the interactions between neuronal sub-populations within and between cell assemblies. Since the mechanisms underlying epileptic disorders should affect such interactions, abnormal level of cross-frequency coupling is expected to provide a signal marker of epileptogenesis. We measured phase-amplitude coupling (PAC), a form of cross-frequency coupling between neural oscillations, in a rodent model of mesial temporal lobe epilepsy...
February 24, 2018: Neurobiology of Disease
Jing-Rong Fan, Heng Li, Hong-Xing Zhang, Qing-Chuan Zheng
The majority of cytochromes P450 play a critical role in metabolism of endogenous and exogenous substrates, some of its products are carcinogens. Therefore, inhibition of P450 enzymes activity can promote the detoxification and elimination of chemical carcinogens. In this study, molecular dynamics (MD) simulations and adaptive steered molecular dynamics (ASMD) simulations were performed to explore the structure features and channel dynamics of three P450 isoforms 2A6, 2A13, and 2E1 bound with the common inhibitor pilocarpine...
February 27, 2018: Biopolymers
Clarissa Vasconcelos de Oliveira, Viviane Nogueira Zorzi, Michele Rechia Fighera, Luiz Fernando Freire Royes, Ana Flávia Furian, Mauro Schneider Oliveira
BACKGROUND: The process by which a brain insult elicits epilepsy is termed epileptogenesis and it is characterized by numerous molecular and functional alterations. Statins are first-line drugs for hypercholesterolemia and related diseases, and display neuroprotective properties in clinical and experimental studies. Considering the importance in developing therapeutic strategies to prevent or modify epileptogenesis, we aimed the present study to test the hypothesis that atorvastatin modifies seizure susceptibility of mice after status epilepticus (SE)...
September 1, 2017: Pharmacological Reports: PR
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