Prof. Kaczmarek is the coordinator of the project, which partners are prof. Asla Pitkanen (University of Eastern Finland, Kuopio, Finlandia), prof. Olli Tenovuo (University of Turku and Hospital District of Southwest Finland, Turku, Finlandia) oraz prof. Stefanie Dedeurwaerdere (University of Antwerp, Antwerpia, Belgia).
Traumatic brain injury, TBI is a serious but poorly understood health problem. Significant complication often resulting from TBI is the development of post-traumatic epilepsy, PTE. There is convincing evidence that synaptic plasticity changes may contribute both favourably (pro-regenerative) as well as unfavourably (epilepsy) to the neuronal response to TBI. Changes stimulated by the TBI are controlled, among other, by the extracellular matrix, ECM. Metalloproteinases (especially MMP-9) as well as serine protease such as urokinase-type plasminogen activator (uPA) and its receptor uPAR greatly contribute to this process. Numerous recently gathered experimental data point to significant role of MMP-9 in synaptic plasticity. The role of this enzyme in PTE has not yet been understood. Similarly very little is known about the uPA/uPAR system in these phenomena. It should be stressed that the extracellular location of both MMP-9 as well as uPA makes them particularly attractive potential targets for future pharmacological therapeutic interventions. In this research project we plan to experimentally verify the hypothesis that MMP-9 and uPA/uPAR contribute to reorganisation of neural circuits leading to post-traumatic epilepsy. We will focus on two molecular systems, since data suggest their involvement in other epilepsy models. Partners of this consortium possess excellent tools and knowledge to study these molecules.