Table of Contents
Epilepsy Research and Treatment
Volume 2011 (2011), Article ID 758407, 11 pages
http://dx.doi.org/10.1155/2011/758407
Research Article

Characterization of the Gene Expression Profile of Human Hippocampus in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis

1Department of Neurosurgery, University Hospital Zurich, 8091 Zurich, Switzerland
2Department of Neurology, University Hospital Zurich, 8091 Zurich, Switzerland
3Department of Psychiatry, University Hospital Zurich, Culmannstrasse 8, 8091 Zurich, Switzerland
4Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland
5Institute for Clinical Chemistry, University of Regensburg, 93040 Regensburg, Germany
6Department of Human Anatomy and Histology, Medical School, Bari University, 70124 Bari, Italy

Received 2 September 2010; Revised 10 December 2010; Accepted 1 January 2011

Academic Editor: Giangennaro Coppola

Copyright © 2011 Julio Lachos et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

One of the main putative causes of therapy refractory epilepsy in mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis is the overexpression of multidrug transporters (MDTs) at the blood-brain barrier (BBB). It steps up the removal of antiepileptic drugs (AEDs) out of the brain cells across the BBB resulting in a low concentration of AEDs within the target cells. Some of the mechanisms of AED resistance are most likely to be genetically determined. To obtain more information about the underlying pathophysiology of intractability in epilepsy, we compared the global gene expression profile of human hippocampus and hippocampal-derived microvascular endothelial cells from MTLE with HS patients and controls. At the level of MDT, a significant up-regulation was found for ABCB1 (P-gp), ABCB2, ABCB3, and ABCB4, which was mainly related to endothelial cells. The data on the MDT were validated and extended by quantitative RT-PCR. Surprisingly, inflammatory factors such as interleukins (IL-1α, IL-1β, IL-6, and IL-18) and cytokines (TNF-α and TGF-β1) were found to be up-regulated in hippocampal parenchyma. The overexpression of P-gp, IL-1β, and IL-6 was also confirmed by immunohistochemistry (IHC). Our results suggest that complex expression changes of ABC-transporters may play a decisive role in pharmacoresistance in MTLE. Further studies on the new and unexpected overexpression of inflammatory cytokines may unlock hitherto undiscovered pathways of the underlying pathophysiology of human MTLE.