Current Neuropharmacology - Volume 16, Issue 1, 2018

Background: Sleep and epilepsy are mutually related in a complex, bidirectional manner. However, our understanding of this relationship remains unclear. Results: The literatures of the neurobiological basis of the interactions between sleep and epilepsy indicate that non rapid eye movement sleep and idiopathic generalized epilepsy share the same thalamocortical networks. Most of neurotransmitters and neuromodulators such as adenosine, melatonin, prostaglandin D2, serotonin, and histamine are found to regulate the sleep-wake behavior and also considered to have antiepilepsy effects; antiepileptic drugs, in turn, also have effects on sleep. Furthermore, many drugs that regulate the sleep-wake cycle can also serve as potential antiseizure agents. The nonpharmacological management of epilepsy including ketogenic diet, epilepsy surgery, neurostimulation can also influence sleep. Conclusion: In this paper, we address the issues involved in these phenomena and also discuss the various therapies used to modify them.

Background: Epilepsy is a chronic brain disease that is caused by various factors and characterized by recurrent, episodic and temporary central nervous system dysfunction which results due to excessive discharge of brain neurons. In the past decades, despite the continuous development of antiepileptic drugs, there are still many patients with epilepsy progressing to drugresistant epilepsy. Currently, surgical treatment is one of important way to cure drug-resistant epilepsy. Methods: Data were collected from Web of Science, Medline, Pubmed, through searching of these keywords: “surgery” and “drug-resistant epilepsy”. Results: An increasing number of studies have shown that surgery plays an important role in the treatment of drug-resistant epilepsy. Moreover, the comprehensive treatment mainly based on surgery can achieve the remission and even cure of drug-resistant epilepsy. Conclusion: In this review, we discuss the pathogenesis of drug-resistant epilepsy and the comprehensive treatment mainly based on surgery; this review may provide a reference for the clinical treatment of drug-resistant epilepsy.

Background: Epilepsy is a syndrome of brain dysfunction caused by spontaneous, abnormal discharge. Many anti-epileptic drugs have developed in past decades. 5-HT is an important neurotransmitter in the central and peripheral nervous system of the human body which is involved in a number of physiological activities, such as sensation, movement, and behavior. 5-HT subtype have been divided into seven sub-groups from 5-HT1 to 5HT7. However, the role of 5-HT3 receptor on epilepsy is unclear. Therefore, in this article, the possible role of 5-HT3 receptor on epilepsy was systemically reviewed. Methods: Data were collected from Web of Science, Medline, Pubmed, Scopus, through searching of these keywords: “5-HT3” and “epilepsy”. Results: An increasing number of studies have shown that the activation of the 5-HT3 receptor can inhibit epileptic seizures, while inhibition of the 5-HT3 receptor can promote spike waves. Conclusion: In this review, we discuss the relationship between the 5HT3 receptor and epilepsy; this review may provide a new insight for clinical application of epilepsy treatment.

Background: Epilepsy is one of chronic severe neurological disorders possess to recurring seizures. And now anti-epileptic drugs are only effective in less than one third of epilepsy patients, and biomarkers predicting are not available when the specific antiepileptic drugs treated. Advanced studies have showed that miRNA may be a key in the pathogenesis of epilepsy beginning in the early 2000 years. Several target genes and pathways of miRNA which related to the therapeutic methods to epilepsy. Method: We searched PubMed from Jan 1,2000 to Jan 1, 2017, using the terms “epilepsy AND microRNA AND biomarker” and “seizure AND microRNA AND biomarker”. We selected articles that featured novel miRNAs in vivo epilepsy models and patients. We then selected the most relevant articles based on a subjective appraisal of their quality and mechanistic insight that could be relevant to epilepsy. Results: Decrease the expression of has-miR134 could be a potential non-invasive biomarker to use in diagnosis for the epilepsy patients for using hsa-miR-134 also be identified to distinguish patients with and without epilepsy. miR-181a show significant downregulation in the acute stage, but up regulation in the chronic stage and in the latent stage there is no changing and how about this phenomenon appearance in different stage still should be discussed in the future. Besides that, miR- 146a can down-regulated in the patients using genome-wide for serum in circulating miRNAs.miR- 124, miR-199a, and miR-128 etc. could be a candidate for the biomarker in future. miR-15a-5p and -194-5p down-regulated in epilepsy patients, in the future, it may be used as a novel biomarker for improve diagnosis. Conclusion: These observations give a chance that new development for diagnosis and treatment of epilepsy patients. Advanced technique and miRNA combination may product more effective roles in epilepsy and other disease. These reports will be available to solve the application of miRNAs as biomarkers and novel therapy approaches for epilepsy. In summary, researcher who focus on miRNAs should be understanding of the causes, treatment, and diagnosis of epilepsy. exploration of any of these effects on the efficacy of these drugs is worthwhile.

Background: Epilepsy is a common neurological disease characterized by abnormal temporary discharge of neurons in the central nervous system. In recent years, studies have revealed the localization and changes in the density of neuropeptides, such as substance P (SP) in the pathogenesis of epilepsy. This review is a concise overview of SP and their physiologic and pathologic functions on regulating epilepsy, and the underline mechanisms. Methods: We research and collect relative online content for reviewing the effects of SP in Epilepsy. Results: The SP/NK-1 receptor system may induce seizures and play an important role in status epilepticus and in experimental animal models of epilepsy. Newest studies show that several mechanisms may explain the excitatory effects of the SP/NK-1 receptor signaling pathway in epilepsy. By binding to the NK-1 receptor, NK-1 receptor antagonists may block the pathophysiological effects of SP, and further studies are needed to confirm the possible anti-epileptic activity of NK-1 receptor antagonists. Conclusion: SP plays crucial roles on through binding with NK-1 receptor during epilepsy pathologic processing, and the NK-1 receptor is receiving a great attention as a therapeutic target for treating epilepsy. Thus, the use of NK-1 receptor antagonists for the treatment of epilepsy should be investigated in further studies.

Background: Choline alfoscerate (α-GPC) and Cytidine 5'-diphosphocholine (CDPCholine) are both acetylcholine precursors and are considered to act as pro-cholinergic nootropic agents. Acetylcholine precursors have also recently found frequent use in the neurology clinic. Stroke and many types of dementia have been shown to respond favorably after treatment with these agents, not only in terms of cognitive dysfunction but also behavioral and psychological symptoms. The primary mechanisms of Acetylcholine precursors are the following: 1) Acetylcholine precursors themselves are used in the biosynthesis of acetylcholine and 2) byproducts like glycerophosphate have protective functions for neuronal phospholipids. However, whether acetylcholine precursors have a similar effect in treating cognitive impairment in patients with epilepsy remains controversial. Methods: Our previous studies investigating acetylcholine precursors in seizure-experienced animals have produced variable results that were dependent on the timing of administration. Results: Early administration of CDP-choline immediately after seizure increased neuronal death, blood-brain barrier (BBB) disruption and microglial activation in the hippocampus. However, administration of α-GPC starting 3 weeks after seizure (late administration) improved cognitive function through reduced neuronal death and BBB disruption, and increased neurogenesis in the hippocampus. Conclusion: These seemingly contradictory results may be attributed to both epileptogenic features and neuroprotective functions of several acetylcholine precursors.

Background: The protective value of vaccines to the public has made vaccines among the major public health prophylactic measures through the entire history. However, there has been some controversy about their safety; particularly concerns have been rising about febrile seizures (FS). Vaccination was found to be the second most common cause of FS. Methods: We research and collect relative online content for reviewing the effects of vaccine in FS. Results: there is no causal relationship between FS and vaccination. This relationship is complex by other factors, such as age, genetic inheritance, type of vaccine, combination of different types of vaccines and the timing of vaccination. Conclusion: In order to reduce FS after vaccination, it is important to understand the mechanism of epilepsy and relationship between specific vaccines and FS. Parents should be informed that some vaccines could be associated with an increased risk of FS, particularly, in children with personal and family history of FS. Children with genetic epilepsy syndrome are prone to seizures and certain vaccinations should be avoided in these children. It is highly recommended to choose vaccines with lower risk of developing FS and to administer these vaccines during the low risk window of immunizations schedule.

Background: Epilepsy is a syndrome of brain dysfunction induced by the aberrant excitability of certain neurons. Despite advances in surgical technique and anti-epileptic drug in recent years, recurrent epileptic seizures remain intractable and lead to a serious morbidity in the world. The ketogenic diet refers to a high-fat, low-carbohydrate and adequate-protein diet. Currently, its beneficial effects on epileptic seizure reduction have been well established. However, the detailed mechanisms underlying the anti-epileptic effects of ketogenic diet are still poorly understood. In this article, the possible roles of ketogenic diet on epilepsy were discussed. Methods: Data was obtained from the websites including Web of Science, Medline, Pubmed, Scopus, based on these keywords: “Ketogenic diet” and “epilepsy”. Results: As shown in both clinical and basic studies, the therapeutic effects of ketogenic diet might involve neuronal metabolism, neurotransmitter function, neuronal membrane potential and neuron protection against ROS. Conclusion: In this review, we systematically reviewed the effects and possible mechanisms of ketogenic diet on epilepsy, which may optimize the therapeutic strategies against epilepsy.

Background: Epilepsy is the second most common disease caused by multiple factors and characterized by an excessive discharge of certain neurons in the nervous system. Cerebrovascular disease, including stroke, is viewed as the most common cause of epilepsy in the elderly population, accounting for 30%-50% of the newly diagnosed cases of epilepsy cases in this age group. Methods: Data were collected from Web of Science, Medline, Pubmed, Scopus, through searching of these keywords: “Stroke” and “epilepsy”. Results: Depending on the underlying cerebrovascular disease, 3%-30% of patients after stroke may develop post-stroke epilepsy (PSE), which has a negative effect on stroke prognosis and the quality of life. Conclusion: In this review, we summarized new aspects emerging from research into PSE, including definition, epidemiology, risk factors, mechanism, accessory examination and treatment strategies for post-stroke epilepsy, which will enrich our knowledge of this disorder.

Background: Epilepsy is one of the most common neurological disorders worldwide, with about 80 percent of cases thought to be in developing nations where it is mostly linked to superstition. The limited supply, high cost as well as low efficacy and adverse side effects of antiepileptic drugs (AEDs) is a matter of major concern. Herbal medicine has always been traditionally part of treatment of epilepsy. Herbal medicines are generally well tolerated, with fewer side effects. Method: To highlight some herbal extracts that have been studied for their anticonvulsant activity in animal models, literature search from PubMed and Science Direct, was performed. The keywords for the search consisted of combinations of the following terms: Herbal antiepileptic and/or anticonvulsant, botanicals + epilepsy. Literature published in the last five years was considered. Results: Eighteen (18) anticonvulsant herbal agents are reported and discussed. Experiments mostly consisted of phenotypic screens in rodents, with little diversity in screening methods. In most experiments, the tested extracts prolonged the time to onset of seizures and decreased their duration. Most experimenters implicate potentiation of GABAergic activity as the mode of action of the extracts, even though some experimenters did not fully characterise the bioactive chemical composition of their extracts. Conclusion: Potential herbal remedies have shown positive results in animal models. It remains unclear how many make it into clinical trials and eventually making part of the AED list. More rigorous research, applying strict research methodology with uniform herbal combinations, as well as clinical studies are urgently needed.

Background: The effects of drugs on driving performance should be checked with drug concentration in the brain and at the same time with the evaluation of both the behavioural and neurophysiological effects. The best accessible indicator of this information is the concentration of the drug and/or metabolites in blood and, to a certain extent, oral fluid. We sought to review international studies on correlation between blood and oral fluid drug concentrations, neurological correlates and cognitive impairment in driving under the influence of drugs. Methods: Relevant scientific articles were identified from PubMed, Cochrane Central, Scopus, Web of Science, Science Direct, EMBASE up to April 2017. Results: Up to 2010, no epidemiological studies were available on this matter and International scientists suggested that even minimal amounts of parent drugs in blood and oral fluid could affect driving impairment. More recently, epidemiological data, systematic reviews and meta-analysis on drugged drivers allowed the suggestion of impairment concentration limits for the most common illicit drugs. These values were obtained comparing driving disability induced by psychotropic drugs with that of established blood alcohol limits. Differently from ethyl alcohol where both detection methods and concentration limits have been well established even with inhomogeneity of ranges within different countries, in case of drugs of abuse no official cut-offs have yet been established, nor any standardized analytical protocols. Conclusion: Multiple aspects of driving performance can be differently affected by illicit drugs, and even if for few of them some dose/concentration dependent impairment has been reported, a wider knowledge on concentration/impairment relationship is still missing.

Background: Widespread protein aggregation occurs in the living system under stress or during aging, owing to disturbance of endoplasmic reticulum (ER) proteostasis. Many neurodegenerative diseases may have a common mechanism: the failure of protein homeostasis. Perturbation of ER results in unfolded protein response (UPR). Prolonged chronical UPR may activate apoptotic pathways and cause cell death. Methods: Research articles on Sigma-1 receptor were reviewed. Results: ER is associated to mitochondria by the mitochondria-associated ER-membrane, MAM. The sigma-1 receptor (Sig-1R), a well-known ER-chaperone localizes in the MAM. It serves for Ca2+-signaling between the ER and mitochondria, involved in ion channel activities and especially important during neuronal differentiation. Sig-1R acts as central modulator in inter-organelle signaling. Sig-1R helps cell survival by attenuating ER-stress. According to sequence based predictions Sig-1R is a 223 amino acid protein with two transmembrane (2TM) domains. The X-ray structure of the Sig-1R [1] showed a membrane-bound trimeric assembly with one transmembrane (1TM) region. Despite the in vitro determined assembly, the results of in vivo studies are rather consistent with the 2TM structure. The receptor has unique and versatile pharmacological profile. Dimethyl tryptamine (DMT) and neuroactive steroids are endogenous ligands that activate Sig-1R. The receptor has a plethora of interacting client proteins. Sig-1R exists in oligomeric structures (dimer-trimer-octamer-multimer) and this fact may explain interaction with diverse proteins. Conclusion: Sig-1R agonists have been used in the treatment of different neurodegenerative diseases, e.g. Alzheimer's and Parkinson's diseases (AD and PD) and amyotrophic lateral sclerosis. Utilization of Sig-1R agents early in AD and similar other diseases has remained an overlooked therapeutic opportunity.