Day :
- Epilepsy Therapeutic & Drug Therapy | Epileptogenesis | Neurobiology of Epilepsy | Non-Surgical Treatment Of Epilepsy
Location: Webinar
Session Introduction
XQ Deng
Jinggangshan University, China
Title: H3R receptor antagonist in the discovery of antiseizure compounds
Time : 09:30-10:00
Biography:
Xianqing Deng is currently a Professor of Medicinal Chemistry in the Health Science Center of Jinggangshan University, China. He has been Head of the Department of Pharmacy from 2021, Director of Academic Sub-committee of Health Science Center from 2022. Dr Deng is expertised in organic medicinal chemistry and new drug design and discovery. His research focus on the design and synthesis of novel antiseizure, antibacterial, and anticancer drugs. He is also interested in discovery and development of novel active substances from Traditional Chinese Medicine. He has authored more than 60 papers in international peer-reviewed journals and a current Hills Index of 20 (Web of science). He has been a guest editor of Frontiers in Chemistry and Molecules and a reviewer for more than 20 scientific journals.
Abstract:
Statement of the Problem: Epilepsy is the second most common neurological disease after cerebrovascular disease. Chronic and recurrent epilepsy not only cause physical damage such as memory loss and emotional expression disorder, but also reduce the quality of daily life of patients, increasing their psychological burden, and leading to a high proportion of accidental deaths. The third generation of antiseizure drugs (ASDs) represented by Eslicarbazepina and Brivaracetam showed better antiseizure effect, pharmacokinetics and safety. However, these drugs have not reduced the proportion of refractory epilepsy or exhibited trauma repair.
Methodology & Theoretical Orientation: With the application of target-based design in antiepileptic drug discovery, an increasing number of target-based antiepileptic active molecules have been discovered. The histamine H3 receptor is a promising new target for antiepileptic treatment. The use of the histamine H3 receptor as a target for epilepsy treatment has been confirmed since 2001. Unfortunately, pharmacologists have not paid too much attention to it, and no antiseizure drug based on the histamine H3 receptor was approved. This study is aim to discover new antiseizure drugs based on histamine H3 receptor(H3R).
Findings: The H3R antagonist provided protection in MES-induced seizure model. What is more, H3R antagonist repaired the damaged hippocampal neurons. Some antiseizure molecules has been identified from a large number of H3R antagonists, and the antiseizure activity was positively related to their H3R inhibitory on the premise of ensuring a certain lipid water Partition coefficient. And their antiepileptic activity can be reversed by H3R agonist RAMH.
Conclusion & Significance: H3R is a potent target for the treatment of epilepsy. H3R antagonist not only inhibit the seizure, but also repair the damaged hippocampal neurons coused by epilepsy. Discovery of new antiseizure drugs among H3R antagonistss is practicable and encouraging.
Maryam Rahimi-Tesiye
Shahid Beheshti University, Iran
Title: ATM, a new therapeutic target in the treatment of epilepsy
Time : 10:00-10:30
Biography:
Maryam Rahimi-Tesiye working as Faculty of Life Science and Biotechnology, Shahid Beheshti University, Tehran, Iran
Abstract:
Introduction: Epilepsy, one of the most common neurological disorders, is associated with reversible seizures, indicating the abnormality of the brain circuits. Different genetic and environmental factors as well as brain tumors are involved in the development of the disease. However, its molecular mechanism is not well understood [1]. In this study, changes in the microenvironment around brain tumors and changes in gene expression of astrocytes, which are involved in epileptogenesis, have been investigated.
Method: The samples with GSE32534 were downloaded from the GO database, then R package “limma” was applied to determine DEGs. Using the Log2FC criterion, -4.362≤ Log2FC ≤ -2.000 and P-value <0.05, 709 highly under-expressed genes were selected and entered into the STRING database for PPI analysis. The network was then rebuilt in Cytoscape software and finally, 99 hub genes with a high score of degree, betweenness, and closeness centrality were selected. Enrichment analysis of these hub genes was performed in Gaphi software to determine the modules.
Results and discussion: Hub genes with the highest scores were mainly involved in biological processes such as cell division, neuronal differentiation, migration, regulation of neurotransmitters, etc. Based on the analysis ATM gene, encodes a serine/threonine kinase and activates P53 in response to DNA double-strand breaks, [2] received the highest score considering all three parameters. ATM is involved in neurological processes such as neuronal survival, proliferation, and synaptic vesicle recycling [3,4] play key role in regulating neurotransmission and the proper functioning of neurons, and many anticonvulsant drugs target such functions [5]. Enrichment analysis revealed the network formed by ATM is mainly involved in glioblastoma signaling pathways, DNA IR- double strand breaks, P53 signaling, and cell cycle.
Conclusion: It can be concluded that down-regulation of ATM through triggering the above pathways can induce epileptogenesis and its targeting can be a new therapeutic goal.
Saghi Hakimi Naeini
Shahid Beheshti University, Iran
Title: The protective effect of glycitin on pentylenetetrazole-induced seizures in male wistar rats
Time : 11:30-12:00
Biography:
I am Saghi Hakimi Naeini and I was born in Iran in 1995. I am a Ph.D. candidate in Biological Sciences- Animal Physiology in the faculty of Life Sciences and Biotechnology at Shahid Beheshti University. I graduated with a bachelor's degree in Biological sciences in 2017 from the University of Shahid Beheshti and a master's degree in Biochemistry in 2020 from the University of Tarbiat Modares. I was the highest-ranked student among all B.Sc. and M.Sc. students and was admitted to postgraduate education (M.Sc. and Ph.D.) without taking the National Entrance Exam (quota of Exceptional Talents). In addition, I have been selected to use the facilities of National Elites Foundation since 2015. currently, as a Ph.D. candidate, I am the first ranked student and have done extensive studies in the field of Neuroscience and Neuroendocrinology. I am very interested in neurological disorders such as epilepsy and its treatment.
Abstract:
Introduction:
Epilepsy is a neurological disorder affecting millions of people and causes recurring seizures. Glycitin is a flavonoid found in soybeans and have various pharmacological properties, including anti-inflammatory, antioxidant, and neuroprotective effects. However, the effects of glycitin on pentylenetetrazole (PTZ)-induced seizures in Wistar rats have not been extensively investigated. In this study, we investigated the potential anticonvulsant effect of glycitin in a rat model of PTZ-induced seizures.
Materials and methods :
Adult Wistar rats were obtained from Shahid Beheshti Medical University. Rats were kept under constant conditions. PTZ and glycitin were purchased from Sigma, USA. A total of 36 male Wistar rats were divided into 6 groups with 6 rats in each group. The first group received saline only, while the second group received saline followed by PTZ (35 mg. kg−1) after 30 minutes. The third to six received phenobarbital (30 mg. kg−1) and glycitin (5, 10, and 20 mg. kg−1) respectively, followed by PTZ after 30 minutes. All injections were administered once every 48 hours for a duration of 21 days via intraperitoneal route. The severity of seizures was assessed using a score adapted from the Racine score, which ranges from 0 to 5. Seizures were recorded for a period of 30 minutes after PTZ injection.
Results:
The analysis of seizure scores showed that the groups receiving glycitin had delayed and less severe seizures compared to the group receiving PTZ after saline. Specifically, the group receiving 5 mg. kg−1 of glycitin showed the most significant reduction in seizure score compared to the PTZ group.
Conclusion:
This study demonstrates that glycitin has anticonvulsant effects in a PTZ-induced seizure model in male Wistar rats. The delayed and less severe seizures observed in the groups receiving glycitin. Further studies are needed to determine the mechanisms underlying its anticonvulsant effects.
K V Shivanand reddy
Nizams Institute of Medical Sciences, India
Title: Getting the best outcomes from epilepsy surgery
Time : 12:30-13:00
Biography:
Abstract:
Neurosurgery is an underutilized treatment that can potentially cure drugâ€refractory epilepsy. Careful, multidisciplinary presurgical evaluation is vital for selecting patients and to ensure optimal outcomes. Advances in neuroimaging have improved diagnosis and guided surgical intervention. Invasive electroencephalography allows the evaluation of complex patients who would otherwise not be candidates for neurosurgery. We review the current state of the assessment and selection of patients and consider established and novel surgical procedures and associated outcome data. We aim to dispel myths that may inhibit physicians from referring and patients from considering neurosurgical intervention for drugâ€refractory focal epilepsies.