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1 Acta Neurobiologiae Experimentalis

1 2011

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Expression and function of extracellular matrix metalloproteinase-9 in human epilepsy

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Konopka A. , Grajkowska W. , Ziemianska K. , Roszkowski M. , Rysz A. , Koperski L. , Kaczmarek L. , Wilczynski G. , Dzwonek J.

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Focal cortical dysplasia (FCD) is a developmental brain disorder characterized by abnormalities of cytoarchitecture and neuronal morphology. FCD is associated with pharmacologically intractable forms of epilepsy in both children and adults. The mechanisms that underlie FCD-associated seizures are unclear. It is believed that a pathological plasticity, including abnormality of synaptic connections, plays the crucial role in this disease. Recent studies indicate the role of interactions between nerve cells and the extracellular matrix in the processes of plasticity. Matrix metalloproteinases are enzymes, which are able to degrade the extracellular matrix components, so they can play an important role in these interactions. Results of experiments using rodent models showed that extracellular matrix metalloproteinase-9 (MMP-9) can play an important role in epileptogenesis. There is no data demonstrating that MMP-9 is involved in the development of epilepsy in human. The aim of this study was to determine whether MMP-9 might play a role in FCD - related epilepsy. Expression of MMP-9 was investigated in human brain tissue derived from people suffering from epilepsy. The immunohistochemistry and antibody microarray methods were used. The control group consisted of the autopsy brain samples. The results indicate that the expression of MMP-9 in the human brain tissue with FCD is increased. The highest immunoreactivity occurs in cytoplasm of abnormal neurons. Moreover, among the 7 tested matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13), MMP-9 is present in greatest concentration in the FCD tissue homogenates. The results support the hypothesis of the possible role of MMP-9 in the development of human epilepsy and give an opportunity to develop new treatments.