Abstracts

To characterize the gene expression profile of peripheral blood mononuclear cells (PBMC) and brain tissue obtained from patients with intractable epilepsy due to mesial temporal sclerosis (MTS). Candidates for temporal lobectomy were asked to participate in this study. PBMC were isolated using gradient separation on cell preparation tubes. Following temporal lobectomy, the hippocampus (HC) and neocortex (NC) removed were labeled and evaluated for specific pathology and for gene expression. The GeneFilters GF211 DNA array containing known named human genes were used. We compared PBMC gene expression differences between patients with TLE vs. patients with active relapsing remittent multiple sclerosis (RRMS) and normal controls (NL), as well as between the NC, HC and PBMC of MTS patients. Brain tissue and PBMC were available from 5 patients (4 M and 1 F) with MTS. Mean age was 33.6 years (range 16 - 53), and mean disease duration was 18.2 years (range 11 - 29). An increased expression of Complement Component 5 (CC5) an inflammatory anaphylatoxin recognized to be associated with peripheral and brain inflammation showed a 7 fold up regulation in the PBMC of epileptic patients compared to healthy controls and active untreated MS patients. Similar CC5 expression was seen in HC and NC. Seventeen genes were significantly increased in the HC compared with the NC, 214 different genes showed increased expression in NC vs HC while 1445 and 1885 genes were significantly different expressed in PBMC vs. NC and HPC respectively. An increase of two to three fold in gene expression of proteins associated with neural damage and glial activation such as Apolipoprotein D (Apo D), beta2 microglobulin and Glial fibrilary acidic protein (GFAP) were found in the HC compared to NC. Our data suggest glial activation and inflammatory reactive response in the hyppocampus and neocortex. Similar increased gene expression was seen in animal models of Unverricht-Lundborg disease, probably associated with long standing epilepsy. The increased inflammatory gene expression seen in the PBMC as well as in the brain may suggest a neuroprotective role for anti-inflammatory therapies in intractable epilepsy. Additional corroborative gene expression data with control brain tissue and confirmatory tissue immunostaining for these specific genes are underway. (Supported by National MS Society
Novartis)