A Murine Model to Study Epilepsy and SUDEP Induced by Malaria Infection

Paddy Ssentongo; Anna E Robuccio; Godfrey Thuku; Derek G Sim; Ali Nabi; Fatemeh Bahari; Balaji Shanmugasundaram; Myles W Billard; Andrew Geronimo; Kurt W Short; Patrick J Drew; Jennifer Baccon; Steven L Weinstein; Frank G Gilliam; José A Stoute; Vernon M Chinchilli; Andrew F Read; Bruce J Gluckman; Steven J Schiff

doi:10.1038/srep43652

A Murine Model to Study Epilepsy and SUDEP Induced by Malaria Infection

Sci Rep. 2017 Mar 8:7:43652. doi: 10.1038/srep43652.

Authors

Paddy Ssentongo^{1

2

3}, Anna E Robuccio^{1

2

3}, Godfrey Thuku^{1

2}, Derek G Sim^{4

5}, Ali Nabi^{1

2}, Fatemeh Bahari^{1

2}, Balaji Shanmugasundaram^{1

2}, Myles W Billard^{1

2}, Andrew Geronimo^{1

2

6}, Kurt W Short^{1

2

6}, Patrick J Drew^{1

2

6

7}, Jennifer Baccon^{6

8}, Steven L Weinstein⁹, Frank G Gilliam^{6

10}, José A Stoute¹¹, Vernon M Chinchilli³, Andrew F Read^{4

5}, Bruce J Gluckman^{1

2

6

7}, Steven J Schiff^{1

2

4

6

12}

Affiliations

¹ Center for Neural Engineering, Penn State University, University Park, Pennsylvania 16802, USA.
² Department of Engineering Science and Mechanics, Penn State University, University Park, Pennsylvania 16802, USA.
³ Department of Public Health Sciences, Penn State College of Medicine, Hershey, Pennsylvania 17033, USA.
⁴ Center for Infectious Disease Dynamics, Penn State University, University Park, Pennsylvania 16802, USA.
⁵ Departments of Biology and Entomology, Penn State University, University Park, Pennsylvania 16802, USA.
⁶ Department of Neurosurgery, Penn State College of Medicine, Hershey, Pennsylvania 17033, USA.
⁷ Department of Bioengineering, Penn State University, University Park, Hershey, Pennsylvania, 16803, USA.
⁸ Department of Pathology, Penn State College of Medicine, Hershey, Hershey, Pennsylvania 17033, USA.
⁹ Department of Neurology, Children's National Medical Center, George Washington University, Washington, DC 20010, USA.
¹⁰ Department of Neurology, Penn State College of Medicine, Hershey, Hershey, Pennsylvania 17033, USA.
¹¹ Department of Medicine, Penn State University College of Medicine, Hershey, Pennsylvania 17033, USA.
¹² Department of Physics, Penn State University, University Park, Pennsylvania, 16803, USA.

Abstract

One of the largest single sources of epilepsy in the world is produced as a neurological sequela in survivors of cerebral malaria. Nevertheless, the pathophysiological mechanisms of such epileptogenesis remain unknown and no adjunctive therapy during cerebral malaria has been shown to reduce the rate of subsequent epilepsy. There is no existing animal model of postmalarial epilepsy. In this technical report we demonstrate the first such animal models. These models were created from multiple mouse and parasite strain combinations, so that the epilepsy observed retained universality with respect to genetic background. We also discovered spontaneous sudden unexpected death in epilepsy (SUDEP) in two of our strain combinations. These models offer a platform to enable new preclinical research into mechanisms and prevention of epilepsy and SUDEP.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Death, Sudden / etiology*
Disease Models, Animal
Electroencephalography
Epilepsy / complications*
Epilepsy / diagnosis
Epilepsy / etiology*
Epilepsy / mortality
Malaria, Cerebral / complications*
Malaria, Cerebral / parasitology
Malaria, Cerebral / pathology
Male
Mice
Plasmodium berghei
Survival Analysis