Abstracts

Disruption of the blood-brain barrier (BBB) has been found to be associated with various neurological disorders, including the acquired epilepsies such as temporal lobe epilepsy (TLE). However, it is not known to what extent the BBB integrity changes during epileptogenesis and whether alterations in BBB permeability may contribute to the development of epilepsy. To get more insight into this, we determined BBB permeability in epileptic rat and human and studied the possible consequences of BBB opening for the subsequent progression of TLE., BBB permeability was investigated in the rat at different time points after electrically induced SE using various tracers that bind to albumin. The cellular localization of albumin was further investigated using immunocytochemistry in rat and human epileptic brain specimens. In addition, we investigated whether BBB opening was related to seizure progression., In a rat model for TLE, in which epilepsy develops after an electrically induced status epilepticus (SE), the BBB was most affected 1 day after SE in limbic brain regions. Although a partial recovery took place during the latent period, the BBB was still permeable in the chronic epileptic phase. Tracer deposits (albumin) were found in microglia, astrocytes and neurons. Similarly, albumin extravasation in human was most prominent directly after a fatal SE in astrocytes and neurons, and to lesser extent in hippocampi of temporal lobe epilepsy patients. BBB permeability in chronic epileptic rats was positively correlated to seizure frequency. Artificial opening of the BBB by mannitol in the chronic epileptic phase induced a persistent increase in the number of seizures in the majority of rats., These findings indicate that BBB leakage occurs during the latent and chronic epileptic phase and suggest that this permanent disruption can contribute to the progression of epilepsy., (Supported by the Epilepsy Institute of The Netherlands.)