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Brain Advance Access originally published online on November 22, 2006
Brain 2007 130(2):521-534; doi:10.1093/brain/awl318
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© The Author (2006). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Blood–brain barrier leakage may lead to progression of temporal lobe epilepsy

E. A. van Vliet1,2, S. da Costa Araújo2, S. Redeker3, R. van Schaik2, E. Aronica3 and J. A. Gorter1,2

1 Epilepsy Institute of The Netherlands (SEIN) Heemstede 2 Swammerdam Institute for Life Sciences, Center for Neuroscience Amsterdam, The Netherlands 3 Academic Medical Center, Department of (Neuro)Pathology, University of Amsterdam Amsterdam, The Netherlands

Correspondence to: Dr J. A. Gorter, Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam, The Netherlands E-mail: gorter{at}science.uva.nl

Leakage of the blood–brain barrier (BBB) is associated with various neurological disorders, including temporal lobe epilepsy (TLE). However, it is not known whether alterations of the BBB occur during epileptogenesis and whether this can affect progression of epilepsy. We used both human and rat epileptic brain tissue and determined BBB permeability using various tracers and albumin immunocytochemistry. In addition, we studied the possible consequences of BBB opening in the rat for the subsequent progression of TLE. Albumin extravasation in human was prominent after status epilepticus (SE) in astrocytes and neurons, and also in hippocampus of TLE patients. Similarly, albumin and tracers were found in microglia, astrocytes and neurons of the rat. The BBB was permeable in rat limbic brain regions shortly after SE, but also in the latent and chronic epileptic phase. BBB permeability was positively correlated to seizure frequency in chronic epileptic rats. 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 epileptogenesis and the chronic epileptic phase and suggest that this can contribute to the progression of epilepsy.

Key Words: albumin; seizure; fluorescein; Evans Blue; mannitol; status epilepticus

Abbreviations: BBB, blood–brain barrier; FJB, fluoro-jade B; TLE, temporal lobe epilepsy; SE, status epilepticus

Received June 23, 2006. Revised September 26, 2006. Accepted October 9, 2006.


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