Expertise and current research performed: The A. I. Virtanen Institute (AIVI) for Molecular Sciences at Kuopio University (Kuopion Yliopisto) is a research institute and one of the six biocentres in Finland. The research activities of AIVI are focused on: (1) biotechnology, (2) neurobiology, especially the neurobiology of diseases affecting the central nervous system and development of disease models, (3) molecular medicine, especially gene therapy and gene transfer technology, and (4) biological signalling and imaging. AIVI harbors the Centre of Excellence for Research in Cardiovascular Diseases and Type 2 Diabetes and is included in the Nordic Centre of Excellence in Neurodegeneration. The total number of personnel is approximately 200 (14 group leaders). The AIVI Graduate School includes approximately 90 students. The Institute has also a Master's School with two international MSc programs (including neurobiology). Researchers of the institute publish approximately 100 peer-reviewed scientific articles annually which appear in leading international journals. The Epilepsy Research laboratory focuses on the following preclinical research projects: 1) Development of clinically relevant animal models of temporal lobe epilepsy in rats and mice; 2) Identification of surrogate markers (MRI, CSF proteomics) for epileptogenesis; 3) Identification of molecular mechanisms underlying circuitry reorganization during epileptogenesis with focus on proteinases and their inhibitors; 4) Preclinical analysis of novel antiepileptogenic compounds

Facilities/Equipment: The A.I.Virtanen Institute is equipped with modern histology and molecular biology laboratories with specific equipments available for the present project: Light, fluorescence and confocal microscopes. Laser dissection microscope. Stimulators and amplifiers for production of SE. Fluid percussion devise for induction of trauma. Three video-EEG monitoring units and four licences for Nervus EEG-analysis software. Affymetric system, sequence detection system for quantitative RT-PCR, microarray scanner.

Personnel involved in the project

Principal investigator: Asla Pitkänen (F). Background in medicine, biochemistry, and functional neuroanatomy. Postdoc in neuroanatomy at the Salk Institute, CA in 1989-1992. In 2004-2005 she did sabattical in the University of Pennsylvania, PA, to familiarize with brain injury models. She has served on national and international committees, including Finnish Epilepsy Society, Brain Research Society of Finland, NIH-NINDS, and ILAE. She is Director of Kuopio Brain Research Center. She is a new Secretary-General-elect of FENS. She serves in the Editorial Board of 7 journals. She has given about 100 invited lectures and published 160 original articles on experimental and clinical epilepsy and is an editor of three books. Her research focus is on functional neuroanatomy of the medial temporal lobe, how the connectivity changes during epileptogenesis, and what are the molecular alterations underlying epileptogenic network reorganization.

Jari Nissinen (M). MSc in biochemistry (PhD in preparation) is involved in the production of clinically relevant animal models for human epilepsy. He has worked with animal models of epilepsy since 1993 under supervision of Dr. Asla Pitkänen. His specific skills include electrical stimulations, video-EEG monitoring and analysis, histologic analysis, statistics. He has also be running the preclinical experiments investigating novel antiepileptogenic compounds. Cagri Yalgin (M). PhD student. MD, started his PhD under supervision of Dr. Pitkänen in 2005. His expertise includes laser disection microscopy and molecular profiling. Merja Lukkari (F). chief histology technician since 1993. Her expertise includes fixation of tissue, histochemistry, immunohistochemistry, double- or triple labeling, tract tracing, stereologic cell counting.

Recent relevant publications/patents

1. Pitkänen A, Kharatishvili I, Nissinen J, McIntosh TK. Post-traumatic epilepsy induced by lateral fluid-pecussion brain injury in rats In: Pitkänen A, Schwarzkroin P, Moshe S (Eds.) Animal models of Seizures and Epilepsy, Elsevier, pp. 465-476 (in press).
2. Pirttilä TJ, Manninen A, Jutila L, Nissinen J, Kälviäinen R, Vapalahti M, Immonen A, Paljärvi L, Karkola K, Alafuzoff I, Mervaala E, Pitkänen A. (2005) Increased expression of cystatin c in the dentate gyrus is associated with granule cell dispersion in experimental and human temporal lobe epilepsy. Ann Neurol. 58(2), 211-23.
3. Pitkänen A, Sutula T. (2002) Is epilepsy a progressive disease? Prospects for new therapeutic approaches in temporal lobe epilepsy. The Lancet Neurology 1, 173-181.
4. Mikkonen M, Soininen H, Kaelviaeinen R, Ylinen A, Vapalahti M, Paljaervi L and Pitkänen A. (1998) "Remodeling of neuronal circuitries in human temporal lobe epilepsy: Increased expression of highly polysialylated neural cell adhesion molecule in the hippocampus and the entorhinal cortex". Ann Neurol. 44(6), 923-934.
5. Pitkänen A, Savander V, LeDoux JE. (1997) Organization of intra-amygdaloid circuitries in the rat: an emerging framework for understanding functions of the amygdala. Trends Neurosci. 20, 517-523.