A first-of-its-kind mouse model could lead to an understanding of how cerebral malaria infection leads to the development of epilepsy in children, and to the prevention of seizures. The model was developed in a collaboration between researchers at Penn State's colleges of medicine, engineering, science, and agriculture.
Cerebral malaria is prevalent in children under 5 in developing countries with high malaria incidence. This form of malaria has a high mortality rate and also leads to epilepsy in survivors, with the rate of epilepsy in countries with malaria infections being up to 6 times higher than those in industrialized countries. There are no treatments during the infection that have been shown to reduce the development of epilepsy and it is not yet understood how malaria leads to epilepsy.
"I work in Africa and people tell me about the shockingly high incidence of epilepsy in children and adults," said lead investigator Steven Schiff, professor of neurosurgery, Brush Chair Professor of Engineering Science and Mechanics and Mechanical Engineering and director of the Penn State Center for Neural Engineering.
Children with cerebral malaria often enter a coma and die from complications, and up to 17% of survivors develop epilepsy. As Schiff looked into how to approach the problem, he realized that not much science is available on post-malaria epilepsy, one of the leading causes of epilepsy on the planet.
"A group of us at Penn State decided to put together our expertise and develop an animal model to test what would be the best therapies for children, so they don't get epilepsy after malaria," he said.
Having a model will allow researchers to perform pre-clinical testing to design therapies to prevent epilepsy if given during treatment of malaria infection. The model can also be used to study how malaria and similar infectious diseases cause epilepsy -- a mystery at present.
The researchers developed 4 different variations, giving scientists a suite of tools to study malaria. They reported their results in Scientific Reports.
"It's a suite of models, not just 1 strain of malaria," Schiff said. "This helps protect against a model having a version of the disease that is irrelevant to humans. It's our best shot at developing treatments because there are 4 different parasite-mouse models to use."
The model can also be used to study sudden unexplained death from epilepsy (SUDEP). In certain cases, epileptic seizures can lead to a person not breathing and their heart stopping. Until now, researchers did not have a way to study SUDEP. The model they developed also shows instances of SUDEP, giving scientists an important tool to learn what causes the sudden death. By understanding how epilepsy causes SUDEP, researchers can better develop preventative treatments.
This research was a collaboration between Penn State colleges and departments, bringing together experts in malaria and infectious disease, neurosciences, mechanical engineering, electrical engineering, experimental physics, biology, public health sciences and more. The first author on the paper, Paddy Ssentongo, is an African physician with deep knowledge of the complexities of malaria in Africa. The College of Engineering faculty helped develop the technologies needed to conduct the research. Schiff said that the research could not have happened without the team effort.
Penn State Institute for the Neurosciences, Pennsylvania Department of Health Tobacco CURE Funds, and Citizen's United for Research in Epilepsy funded this research.
Source: News Release
March 23, 2017