Central expression and peripheral levels of MMP-9 and TIMP-1 in patients with temporal lobe epilepsy

Abstract

Purpose

Thirty percent of epilepsy patients are drug-resistant (DR) and, in adults, temporal lobe epilepsy (TLE) is the most common form of DR- epilepsy. Patients with TLE exhibit a neuroinflammatory response associated with blood–brain barrier dysfunction. In this context, the main aim of our study was to evaluate peripheral levels and central expression of MMP-9 and TIMP-1 in TLE patients and assess their association with drug resistance and inflammatory markers.

Methods

Three groups of patients were included, 41 DR-TLE patients, 10 non-DR-TLE patients, and 20 healthy controls (HC). MMP-9 and TIMP-1 were assessed by ELISA in sera in all patients, and by immunohistochemistry and immunofluorescence in the cerebral cortex and hippocampus in a subgroup of DR-TLE patients and 3 controls. Peripheral and central cells phenotypes were determined by flow cytometry and immunohistochemistry, respectively, while cytokines were determined in the two compartments by ELISA.

Results

Central expression of MMP-9 and TIMP-1, and peripheral expression of TIMP-1, were higher in DR-TLE patients than in controls, while peripheral levels of MMP-9 and TIMP-1 were higher in DR-TLE patients compared with non-DRE-TLE patients. MMP-9 levels in serum increased with seizure severity and decreased after successful epilepsy surgery. MMP-9 levels in the serum of DR-TLE patients were positively correlated with several markers of peripheral inflammation, which was not the case in the groups of non-DR-TLE patients and healthy controls. MMP-9 and TIMP-1 expression in the hippocampus of DR-TLE patients correlated positively with various markers of central inflammation. Negative correlations between their peripheral levels and central expression were observed.

Conclusion

MMP-9 and TIMP-1 are markers that seem to be associated to the central and peripheral inflammatory reaction occurring in DR-TLE patients. The significant negative correlations between central and peripheral markers are interesting to note, and further studies need to be carried out to fully understand the complex regulation of these proteins during DR epilepsy.