Epileptic fits, i. e. abnormal excessive neuronal activity in the hippocampus, severely affects nerve cells and can lead to permanent damage. A team of researchers led by Prof. Dr. Carola Haas from the Neurocenter at the University of Freiburg is focusing on changes in the brain anatomy of patients suffering from temporal lobe epilepsy as well as on the molecular and cellular processes underlying the disease. The team’s research focuses on stem cells, granule cell dispersion and the molecule Reelin, which helps migrating neurons reach their proper destination.
Spatial relationships between groups of neurons in the brain are always of functional relevance. However, defective function is not always recognisable from changes in the cell architecture. The term epilepsy refers to a diverse set of symptoms related to the abnormal synchronisation of different brain areas. Temporal lobe epilepsy, which is associated with distinctive pathological structural changes in the brain, spreads from one or both temporal lobes of the brain and leads to recurrent epileptic seizures. Temporal lobe epilepsies, which cannot be treated adequately with medication, mainly arise in the hippocampus. "As the disease progresses, more and more neurons die, the ordered architecture of the different cell types disappears, leading to the scarring of the affected tissue," said Prof. Dr. Carola Haas from the Neurocenter at the University of Freiburg.
After Haas and her team of researchers discovered a connection between epileptic seizures and Reelin deficiency, they conducted systematic studies in mouse models and cell cultures in which they used ion channel drugs to simulate epileptic changes. This enabled them to identify a causal relationship between Reelin deficiency and epileptic seizures. Changes in the tissue of epileptic mice resulted in a lack of Reelin and eventually in the dispersion of granule cells in the hippocampus. The silencing of Reelin in mouse brains using antibodies also led to the dispersion of granule cells. The researchers from Freiburg have just concluded an experiment in which they examined the migration behaviour of granule cells in epileptic hippocampal tissue using confocal microscopes. They found that artificially induced epilepsy caused granule cells to leave their normal site and move through the tissue.
Haas and her team are currently focused on elucidating the molecular mechanisms underlying epileptic changes in the mouse brain that lead to Reelin deficiency. They are also interested in the process of neurogenesis during epileptic seizures, as research suggests that brain areas with high epileptic activity are also the sites with the largest number of young neurons. What links are there between stem cell activity and epilepsy? Haas and her team are also involved in the new BrainLinks-BrainTools cluster of excellence at the University of Freiburg, which brings together basic neurobiological research, clinical research and the emerging field of neurotechnology. Haas and her team envisage that their research will eventually contribute to developing methods involving the targeted application of drugs or the use of brain implants that will help to bring the chaos in the brains of epilepsy patients under control. The team also has a strong interest in the development of a new generation of electrode systems and imaging techniques. A recent paper published by the Freiburg group and their cooperation partners reports on the beneficial effects of astrocytes, a specific type of hippocampal glial cells. They found that astrocytes help reduce long-term damage brought on by epileptic fits. Further studies are needed in order to substantiate the finding that astrocytes have this protective influence. However, the researchers’ findings suggest that it might eventually be possible to bring the electrical thunderstorms in the brain under control.
Further information:Prof. Dr. Carola HaasExperimental Epilepsy Research Department of NeurosurgeryNeurocenterUniversity of FreiburgBreisacher Str. 6479106 FreiburgTel.: +49 (0)761/ 270 52 950Fax: +49 (0)761/ 270 52 951E-mail: carola.haas(at)uniklinik-freiburg.de