| Mesial Temporal Lobe Epilepsy (MTLE) is a progressive neurological disorder and the most frequent type of epilepsy in adults. MTLE is often preceded by an initial insult that after a latent period leads to recurrent seizures. The main aim is to characterize mechanisms of seizure progression in epilepsy. Recent studies indicate that the blood-brain barrier (BBB; a defense mechanism that protects the brain against blood components) may be a new target. BBB leakage has been shown in epileptic humans and animals and is associated with epileptic activity and inflammation. I recently showed that artificial opening of the BBB increased seizure frequency, which is a major break-through in the epilepsy field. However, the precise factors that contribute to progression of epilepsy are not known. It is also not known whether restoration of the BBB could lead to a milder form of epilepsy or even prevent the development of epilepsy. Therefore I want to start an innovative research line and focus on the role of a compromised BBB in the progression of epilepsy using a multidisciplinary approach in a rat model for MTLE. First, I will study whether the extent of BBB disruption during the early epileptogenic phase is predictive of seizure outcome in the chronic epileptic phase using Magnetic Resonance Imaging (MRI) in rats. Since BBB disruption leads to intrusion of (white) blood cells and plasma derived substances I will also use cellular imaging techniques (MR, confocal and voltage sensitive dye imaging) to determine the effects of these compounds on neuronal and glial network dynamics and on seizure progression. Finally, I will study whether anti-inflammatory therapies that restored BBB function in multiple sclerosis have disease modifying therapeutic effects in epilepsy. |
