Research Training Group 2154 - Materials for Brain

Project 9: Anna-Sophia Buschhoff

Epilepsy therapy by local release of antiepileptic drugs

Epilepsy is a chronic disorder of the brain that affects approximately 50 million people worldwide and is, thus, one of the most common neurological diseases. Spontaneous, recurring seizures, caused by aberrant neural activity, are a hallmark feature of epilepsy. These seizures show a broad spectrum of clinical features. Accordingly, different types of epilepsies can be classified. Within this spectrum, absence epilepsy is defined as an idiopathic and generalized form of epilepsy.
In only two-thirds of patients with epilepsy, anticonvulsant drugs (AEDs) show efficacy. One of the major challenges appears to be the effective drug delivery to the central nervous system (CNS) as the agents have to cross the blood-brain barrier (BBB). The approach of this project is to design an intracranial drug delivery system in order to bypass the BBB, locally increase the drug concentration, and avoid side effects caused by systemic drug administration.
This drug delivery approach is investigated in vivo in absence epilepsy rats from Strasbourg (GAERS), as this is a validated model of spontaneous absence epilepsy. These animals show seizures, which closely resemble human absence seizures, characterized by subtle behavioral changes consisting of “behavioral arrest” and rhythmic twitching of the vibrissae and/or jaw muscles. Furthermore, bilateral synchronous spike and wave discharge (SWD) can be measured in the electroencephalogram (EEG). In order to analyze the effects of intracranial drug application on seizure activity, we monitor behavior and record brain signals.