For the first time, researchers have inhibited the development of epilepsy after a brain insult in animals. By using gene therapy to modify signaling pathways in the brain, neurology researchers found that they could significantly reduce the development of epileptic seizures in rats.
"We have shown that there is a window to intervene after a brain insult to reduce the risk that epilepsy will develop," said one of the lead researchers, Amy R. Brooks-Kayal, M.D., a pediatric neurologist at The Children's Hospital of Philadelphia and associate professor of Neurology and Pediatrics at the University of Pennsylvania School of Medicine. "This provides a 'proof of concept' that altering specific signaling pathways in nerve cells after a brain insult or injury could provide a scientific basis for treating patients to prevent epilepsy."
Dr. Brooks-Kayal and Shelley J. Russek, Ph.D., of Boston University School of Medicine were senior authors of the study in the Nov. 1 Journal of Neuroscience.
Working in a portion of the brain called the dentate gyrus, the researchers focused on one type of cell receptor, type A receptors, for the neurotransmitter gamma-aminobutyric acid (GABA). When GABA(A) receptors are activated, they inhibit the repetitive, excessive firing of brain cells that characterizes a seizure. Seizures are thought to occur, at least in part, because of an imbalance between two types of neurotransmitters: the glutamate system, which stimulates neurons to fire, and the GABA system, which inhibits that brain activity.
GABA's inhibitory role is considered particularly important in the dentate gyrus because the dentate gyrus acts as a gateway for brain activity into the hippocampus, an area that is critical to generating seizures in temporal lobe epilepsy, the most common type of epilepsy in children and adults.
GABA(A) receptors are made up of five subunits--proteins that play important roles in brain development and in controlling brain activity. Previous animal research by Dr. Brooks-Kayal's group had found that rats with epilepsy had lower levels of the alpha1 subunits of these receptors and higher levels of alpha4 subunits. Therefore, the researchers used gene delivery to alter the expression of the alpha1 subunit to see if this would have an effect on later seizure development.
To carry the gene that alters the expression of the protein, they used an adeno-associated virus vector, injected into the rats' brains. The researchers later injected the rats with pilocarpine, a drug that causes status epilepticus (SE), a convulsive seizure, shortly after injection.
They then evaluated the rats for later development of spontaneous seizures or epilepsy, which usually occurs after an initial SE injury. Rats that had received the gene therapy had elevated levels of alpha1 proteins and either did not develop spontaneous seizures, or took three times as long to experience a spontaneous seizure, compared to rats that did not receive the delivered gene.
In this short-term study, said Dr. Brooks-Kayal, it was impossible to tell whether the increased alpha1 subunit levels were only suppressing seizures or whether they would permanently prevent epilepsy from developing.
"In people, an initial episode of SE or an injury such as severe head trauma is known to raise the risk of later developing epilepsy, so this study suggests that strategies aimed at modifying signaling pathways in the brain after such an insult may help prevent epilepsy," said Dr. Brooks-Kayal. "The approach would likely be different than in this proof-of-concept animal study that involved injecting agents directly into the brain. This study, does, however, lay the foundation for a potential drug therapy that might act on the same signaling pathways, to prevent epilepsy after a brain insult such as an episode of SE."
John Ascenzi | EurekAlert!
World’s Largest Study on Allergic Rhinitis Reveals new Risk Genes
17.07.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Plant mothers talk to their embryos via the hormone auxin
17.07.2018 | Institute of Science and Technology Austria
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
17.07.2018 | Information Technology
17.07.2018 | Materials Sciences
17.07.2018 | Power and Electrical Engineering