Magnetic devices and therapies are gaining rapid acceptance among some groups, even in the absence of reliable outcome data. This Center is focused upon the potential treatment with electromagnetic fields (EMFs) of fibromyalgia and the sequelae to CVA and closed head trauma. Despite considerable effort, it is still not clear how biological systems might be responding to therapeutically applied EMFs. The development and refinement of this potential new mode of therapy will be advanced considerably by a more explicit understanding of what basic biological processes are responsible for the desired therapeutic effects. This project will examine the effect of therapeutic magnetic fields upon specific neural processes and functions, in the effort to outline potential biosensors for EMFs in the nervous system. The tests will be conducted in vitro upon reasonable cellular reductionist models of events in the nervous system. In each case, EMF effects under basal and stressed conditions will be examined. Specific aims will measure magnetic field effects upon: l) Fiber regeneration by peripheral and central neurons. Primary neurons in culture will be used and the rate of regeneration of neurites measured. 2) Synapse formation and maturation. Cultures of peripheral neurons and muscle, as well as central neurons, will be examined for synapse formation and function at various times after isolation. 3) Calcium signaling via cytosolic transients in nerve and muscle cells. Fura-2 imaging will be used to examine EMF effects on IP3-mediated calcium signaling in primary cultures of muscle and human neuroblastoma cells. 4) Synthesis and release of neurotrophins. The production of NGF at the cellular level by muscle, neuroblastoma and glial cells will be examined. 5) Cell death and neuroprotective gene expression. EMF effects on induction of apoptosis and expression of free-radical scavengers and bcl-2 will be tested. Each of these test areas relates to a biological process involved in the response of the nervous system to injury or disorder and thus may be involved in the therapeutic efficacy of magnetic fields. The results of these largely exploratory experiments will outline likely basic biological processes capable of responding to EMF with a desirable therapeutic effect.