Expertise and current research performed: The “Mario Negri” Institute for Pharmacological Research is a scientific organization for research and education in the biomedical field located in Milan, Italy. The aim of the Institute is to improve the quality of human health and life. Research methods range from the molecular level (molecular biology) to humans (clinical pharmacology and epidemiology). The results of this research help in new drug development and improve the efficacy of those already in use. The Institute's three main fields of interest are: cancer, mental and nervous system disorders, and cardiovascular diseases. The “Mario Negri” Institute consists of about 30 research laboratories organized in 50 units, and a dozen administrative and service facilities. The results of the scientific work done have been published in more than 6,000 reports, which have appeared in leading international journals. The laboratory of Experimental Neurology focuses on preclinical research projects mainly involving the following studies: 1) Molecular and biochemical mechanisms underlying ictogenesis and epileptogenesis including the role of neuroactve peptides and inflammatory mediators; 2) Novel pharmacological targets for anti-ictogenic and anti-epileptogenic effects; 3) Molecular mechanisms of pharmacoresistence; 4) Mechanisms of seizure-induced neuronal cell loss and plasticity. The research is carried out using models of seizures and epileptogenesis in rodents, in particular models of acute seizures, status epilepticus and kindling.

Facilities/Equipment: EEG trace recorders and electrical stimulators; McLab system for online trace acquisition and analysis; IMAGE analyzer; light and fluorescent microscope; confocal microscope; all basic equipments for molecular biology and biochemistry; cell culture and organotypic slice cultures facilities. Core facilities: Animal care Unit; animal housing and maintenance; rooms for radiolabeled tracers and compounds; Confocal microscopy

Personnel involved in the project

Principal investigator: Annamaria Vezzani (F). Background experience in neuropharmacology and neurobiology and she has been working in the field of experimental epilepsy since 1983. She helds the position of Head of the Laboratory of Exp Neurology, Dept of Neuroscience at Mario Negri Inst for Pharmacol Res, Milano, Italy. She has a PhD in Neuropharmacology. She spent a post-doc period at the university of Maryland, baltimore, US in 1983-1984. Member of the Editorial Board of Epilepsia, Epilepsy Currents and Neuroscience. Research interests focus on biochemical and molecular mechanisms involved in the etiopathogenesis of seizures disorders using experimental models of epilepsy and development of novel pharmacological strategies with anticonvulsant and antiepiletogenic activities.

Teresa Ravizza, (F). PhD. Involved in immunohistochemical studies of inflammatory mediators in models of seizures during post-natal development. Working since March 1997 in the Laboratory of Experimental Neurology. Postdoctoral training (2000-2002) in the Laboratory of Developmental Epilepsy at Albert Einstein College of Medicine, Bronx under the supervision of Prof. S.L.Moshè. She has now a permanent position as senior researcher in Laboratory of Experimental Neurology since 2003. Silvia Balosso (F). PhD student. Involved in in vitro studies using primary cultures and organotypic slice cultures and in in vivo studies using models of seizures and epileptogenesis. Degree in Chemistry and Pharmaceutical Tecnology; Training fellow in Pharmacological Research (2001-2003), Laboratory of Experimental Neurology. PhD student since January 2005.

Recent relevant publications/patents

1.        Balosso S, Ravizza T, Perego C, Peschon J, Campbell I, De Simoni MG, Vezzani A. (2005) TNF-Alpha inhibits kainic acid-induced seizures in mice via p75 receptors. Ann Neurol, 57: 804-812.

2.        Rizzi M., Perego C., Aliprandi M., Richichi C., Ravizza T., Colella D., Velísková J., Moshé S.L., De Simoni MG and Vezzani A. (2003) Glia activation and cytokine increase in rat hippocampus by kainic acid-induced status epilepticus during postnatal development. Neurobiol Disease, 14:494-503.

3.        Viviani B., Bartesaghi S., Gardoni F., Vezzani A., Behrens M. M., Bartfai T., Binaglia M., Corsini E., Di Luca M., Galli C.L., Marinovich M. (2003) Interleukin-1ßeta enhances NMDA receptor-mediated intracellular calcium increase through activation of the src family of kinases. J Neurosci, 23: 8692-8700.

4.        Vezzani A., Moneta D., Conti M., Richichi C., Ravizza T., De Luigi A., De Simoni M.G., Sperk, Andell-Jonsson S., Lundkvist J., Iverfeldt K. and Bartfai T. (2000) Powerful anticonvulsant action of IL-1 receptor antagonist upon intracerebral injection and astrocytic overexpression in mice. Proc. Natl. Acad. Sci. USA, 97, 11534-11539.

5.        Vezzani A., Conti M., De Luigi A., Ravizza T., Moneta D., Marchesi F. and De Simoni MG (1999) Interleukin-1ßetaimmunoreactivity and microglia are enhanced in the rat hippocampus by focal kainate application: functional evidence for enhancement of electrographic seizures. J. Neurosci., 19, 5054-5065.