The Effect of Metformin in Experimentally Induced Animal Models of Epileptic Seizure

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Epilepsy is one of the common neurological illnesses which affects millions of individuals globally. Although the majority of epileptic patients have a good response for the currently available antiepileptic drugs (AEDs), about 30-40% of epileptic patients are developing resistance. In addition to low safety profiles of most of existing AEDs, there is no AED available for curative or disease-modifying actions for epilepsy so far.

Objectives

This systematic review is intended to evaluate the effect of metformin in acute and chronic animal models of an epileptic seizure.

Methods

We searched PubMed, SCOPUS, Sciences Direct, and grey literature in order to explore articles published in English from January 2010 to November 2018, using key terms “epilepsy,” “seizure,” “metformin,” “oral hypoglycemic agents,” and “oral antidiabetic drugs”. The qualities of all the included articles were assessed according to the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES).

Results

Out of six hundred fifty original articles retrieved, eleven of them fulfilled the inclusion criteria and were included for final qualitative analysis. In these studies, metformin showed to control seizure attacks by attenuating seizure generation, delaying the onset of epilepsy, reducing hippocampal neuronal loss, and averting cognitive impairments in both acute and chronic models of an epileptic seizure. The possible mechanisms for its antiseizure or antiepileptic action might be due to activation of AMPK, antiapoptotic, antineuroinflammatory, and antioxidant properties, which possibly modify disease progression through affecting epileptogenesis.

Conclusion

This review revealed the benefits of metformin in alleviating symptoms of epileptic seizure and modifying different cellular and molecular changes that affect the natural history of the disease in addition to its good safety profile.

Related collections

Most cited references 86

Record: found
Abstract: found
Article: not found

Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs.

Wolfgang Löscher (2011)

Animal models for seizures and epilepsy have played a fundamental role in advancing our understanding of basic mechanisms underlying ictogenesis and epileptogenesis and have been instrumental in the discovery and preclinical development of novel antiepileptic drugs (AEDs). However, there is growing concern that the efficacy of drug treatment of epilepsy has not substantially improved with the introduction of new AEDs, which, at least in part, may be due to the fact that the same simple screening models, i.e., the maximal electroshock seizure (MES) and s.c. pentylenetetrazole (PTZ) seizure tests, have been used as gatekeepers in AED discovery for >6 decades. It has been argued that these old models may identify only drugs that share characteristics with existing drugs, and are unlikely to have an effect on refractory epilepsies. Indeed, accumulating evidence with several novel AEDs, including levetiracetan, has shown that the MES and PTZ models do not identify all potential AEDs but instead may fail to discover compounds that have great potential efficacy but work through mechanisms not tested by these models. Awareness of the limitations of acute seizure models comes at a critical crossroad. Clearly, preclinical strategies of AED discovery and development need a conceptual shift that is moving away from using models that identify therapies for the symptomatic treatment of epilepsy to those that may be useful for identifying therapies that are more effective in the refractory population and that may ultimately lead to an effective cure in susceptible individuals by interfering with the processes underlying epilepsy. To realize this goal, the molecular mechanisms of the next generation of therapies must necessarily evolve to include targets that contribute to epileptogenesis and pharmacoresistance in relevant epilepsy models. Copyright © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

0 comments Cited 193 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

The role of inflammation in the development of epilepsy

Amna Rana, Alberto Musto (2018)

Epilepsy, a neurological disease characterized by recurrent seizures, is often associated with a history of previous lesions in the nervous system. Impaired regulation of the activation and resolution of inflammatory cells and molecules in the injured neuronal tissue is a critical factor to the development of epilepsy. However, it is still unclear as to how that unbalanced regulation of inflammation contributes to epilepsy. Therefore, one of the goals in epilepsy research is to identify and elucidate the interconnected inflammatory pathways in systemic and neurological disorders that may further develop epilepsy progression. In this paper, inflammatory molecules, in neurological and systemic disorders (rheumatoid arthritis, Crohn’s, Type I Diabetes, etc.) that could contribute to epilepsy development, are reviewed. Understanding the neurobiology of inflammation in epileptogenesis will contribute to the development of new biomarkers for better screening of patients at risk for epilepsy and new therapeutic targets for both prophylaxis and treatment of epilepsy.

0 comments Cited 190 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The consequences of refractory epilepsy and its treatment.

Kenneth D. Laxer, Eugen Trinka, Lawrence J Hirsch … (2014)

Seizures in some 30% to 40% of patients with epilepsy fail to respond to antiepileptic drugs or other treatments. While much has been made of the risks of new drug therapies, not enough attention has been given to the risks of uncontrolled and progressive epilepsy. This critical review summarizes known risks associated with refractory epilepsy, provides practical clinical recommendations, and indicates areas for future research. Eight international epilepsy experts from Europe, the United States, and South America met on May 4, 2013, to present, review, and discuss relevant concepts, data, and literature on the consequences of refractory epilepsy. While patients with refractory epilepsy represent the minority of the population with epilepsy, they require the overwhelming majority of time, effort, and focus from treating physicians. They also represent the greatest economic and psychosocial burdens. Diagnostic procedures and medical/surgical treatments are not without risks. Overlooked, however, is that these risks are usually smaller than the risks of long-term, uncontrolled seizures. Refractory epilepsy may be progressive, carrying risks of structural damage to the brain and nervous system, comorbidities (osteoporosis, fractures), and increased mortality (from suicide, accidents, sudden unexpected death in epilepsy, pneumonia, vascular disease), as well as psychological (depression, anxiety), educational, social (stigma, driving), and vocational consequences. Adding to this burden is neuropsychiatric impairment caused by underlying epileptogenic processes ("essential comorbidities"), which appears to be independent of the effects of ongoing seizures themselves. Tolerating persistent seizures or chronic medicinal adverse effects has risks and consequences that often outweigh risks of seemingly "more aggressive" treatments. Future research should focus not only on controlling seizures but also on preventing these consequences.

0 comments Cited 188 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Ebrahim M. Yimer:

ORCID: http://orcid.org/0000-0003-3140-4967

Journal

Journal ID (nlm-ta): Behav Neurol

Journal ID (iso-abbrev): Behav Neurol

Journal ID (publisher-id): BN

Title: Behavioural Neurology

Publisher: Hindawi

ISSN (Print): 0953-4180

ISSN (Electronic): 1875-8584

Publication date Collection: 2019

Publication date (Electronic): 4 February 2019

Volume: 2019

Electronic Location Identifier: 6234758

Affiliations

Mekelle University, College of Health Sciences, Department of Pharmacology and Toxicology, Ethiopia

Author notes

Academic Editor: Péter Klivényi

Author information

Ebrahim M. Yimer http://orcid.org/0000-0003-3140-4967

Dawit Zewdu Wondafrash http://orcid.org/0000-0003-1127-6443

Abadi Kahsu Gebre http://orcid.org/0000-0002-1975-0085

Article

DOI: 10.1155/2019/6234758

PMC ID: 6378775

SO-VID: f8042ceb-6868-4fd7-854d-5113713fdb10

License:

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 17 September 2018

Date revision received : 8 December 2018

Date accepted : 17 December 2018

Comments

Comment on this article

scite_

Cited by 9

See all cited by

Most referenced authors 1,133

See all reference authors

- Version 1

The Effect of Metformin in Experimentally Induced Animal Models of Epileptic Seizure

Read this article at

Abstract

Background

Objectives

Methods

Results

Conclusion

Related collections

Animal models of intrauterine growth restriction (IUGR)

Most cited references 86

Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs.

The role of inflammation in the development of epilepsy

The consequences of refractory epilepsy and its treatment.

Author and article information

Contributors

Journal

Affiliations

Author notes

Author information

Article

History

Categories

Comments

Comment on this article

Similar content 503

Cited by 9

Most referenced authors 1,133