Abstracts

Identifying potential therapeutic targets for disruption of neuronal networks in epileptogenesis combining systematic review and meta-analysis.

Abstract number : 3.008
Submission category : 1. Translational Research: 1A. Mechanisms / 1A1. Epileptogenesis of acquired epilepsies
Year : 2016
Submission ID : 195773
Source : www.aesnet.org
Presentation date : 12/5/2016 12:00:00 AM
Published date : Nov 21, 2016, 18:00 PM

Authors :
Taylor Anderson, Eastern Virginia Medical School, Norfolk, Virginia; Anthony Chuprin, Eastern Virginia Medical School, Norfolk, Virginia; Gordana Rasic, Eastern Virginia Medical School, Norfolk, Virginia; John DelBianco, Eastern Virginia Medical School, N

Rationale: Experimental research in epileptogenesis using animal models of epilepsy is critical for the discovery of new therapies to prevent epilepsy and to reduce adverse effects and pharmacoresistance. Disruption of the neuronal network plays a key role in epileptogenesis. The goal of this study is to evaluate the currently proposed interventions for epileptogenesis and their contributions, to identify biological mechanisms that can prevent aberrant neural plasticity in epilepsy. Methods: Freely available full-text articles in English were screened and analyzed from the PubMed library. The keyword used was "epileptogenesis," and the search was restricted to publication years between 2007 and 2016. A detailed animal model of epileptogenesis, the number of animals used, the latency period, and the type of interventions performed were inclusion criteria. Articles lacking data required for statistical analysis (e.g. mean, standard deviation, and sample size) were excluded. Data regarding the type, number, and occurrence of spontaneous seizures; density of hippocampal dendritic spines; degree of mossy fiber sprouting; density of microglia; concentration of inflammatory molecules; and type of therapeutic intervention were added to a preformatted database. Then, the data was analyzed accordingly. Results: In this study 1,486 articles have been screened, and 76 articles were included. From a preliminary analysis, 95% of articles utilized rodents as the animal model; 23% of the studies used kindling and 64% used status epilepticus (SE) to induce epileptogenesis. Regarding spontaneous recurrent seizures as a major outcome, 23% of the studies evaluated seizure frequency; 22% evaluated seizure severity; 27% evaluated seizure duration; 6% evaluated amplitude of electrical activity; 10% evaluated threshold for seizure susceptibility, 3% evaluated prevalence of seizure recurrence and 26% evaluated latency period. 32% of the articles demonstrated attenuation of epilepsy development. 56% of the studies conducted a post-SE intervention with 6% using rapamycin. Anti-inflammatory compounds, blocking voltage-gated sodium channels and rampamycin do not prevent epileptogenesis but limit the frequency of seizures.As an outcome of aberrant plasticity, 18% of articles evaluated dendritic spines and mossy fibers sprouting. In addition, 5% of articles evaluated IL-1B and TNF-alpha levels as inflammatory markers. Conclusions: Despite the use of different scales and relatively small sample sizes, modulation of inflammatory pathway activation, voltage-gated sodium channels, and the mTOR pathway need to be further explored for anti-aberrant plasticity in epileptogenesis. Future studies should standardize measurement of seizure occurrence to be more amenable to large-scale analysis. Few studies report adverse effects, toxicity, survival rate, animal age, and evaluation of seizure recurrence over time. Our preliminary data indicate several potential modulators of neuronal networks, while pointing to the need for collaboration among investigators. Funding: N/A
Translational Research