Dr. Craviso's background is in neurobiology and upon her arrival at the School of Medicine in 1990, her research interest focused on the mechanisms underlying both the short, and long–term regulation of the synthesis and secretion of the catecholamines norepinephrine and epinephrine, using isolated bovine adrenal chromaffin cells as a model of neural–type cells. In the late 1990s her research took an exciting new direction that was aimed at understanding "non-thermal" cellular responses evoked by externally applied electromagnetic fields (EMFs), the goal being to lay the foundation for establishing EMF approaches for probing and manipulating cellular function that could be exploited and transitioned into novel EMF-based therapeutic applications. This new direction, which also employed chromaffin cells as one of her in vitro model systems (intact skeletal muscle being another), was undertaken in collaboration with Dr. Indira Chatterjee, an electrical engineering professor in the College of Engineering. Funded projects included investigations of 60 Hz electric and magnetic fields on neurosecretion (NIH-funded), investigations of radiofrequency and microwave radiation on neurosecretion, and investigations of millimeter waves on skeletal muscle contraction (both projects funded by the Air Force Office of Scientific Research). Her research currently is focused on the effects of nanosecond, megavolt–per–meter pulsed electric fields on neurosecretion (funded by the Air Force Office of Scientific Research until 2019). Collaborators on this project include Dr. Normand Leblanc, Professor of Pharmacology, Dr. Indira Chatterjee, and Dr. P. Thomas Vernier at the Frank Reidy Research Center for Bioelectrics in Norfolk, VA. Dr. Craviso is a member of the Society for Neuroscience, the Bioelectromagnetics Society and the American Association for the Advancement of Science.
Interaction of electromagnetic fields with excitable cells; exploring the potential for nanosecond duration electric pulses of high intensity as a new, bioelectric approach for stimulating neural cells.
Within the past decade, deep brain stimulation that delivers microsecond duration electric pulses to specific brain regions via surgically implanted electrodes has become an established treatment for movement disorders (e.g., Parkinson's disease, tremor and dystonia) in patients who either do not respond to drug treatment or else experience unacceptable drug side effects. Other potential clinical applications of deep brain stimulation include treatment of epilepsy, pain and neurological disorders such as depression. My research builds on the growing clinical acceptance of electric stimulation for neuromodulation by focusing on a new type of electric stimulus, high intensity (> 1 megavolt-per-meter), nanosecond duration electric pulses, as an emerging technology for altering neural cell excitability. In a highly interdisciplinary collaborative effort, I have been exploring the effectiveness of nanoelectropulses less than 10 ns in duration for evoking neurosecretion. Using adrenal chromaffin cells as a model of neural-type cells, we found that a 5 ns, 5 megavolt-per-meter electric pulse causes activation of voltage-gated calcium channels, which leads to calcium influx and the exocytotic release of the catecholamines epinephrine and norepinephrine. This secretory response not only mimics the stimulation of catecholamine release evoked in vivo by the neurotransmitter acetylcholine but also occurs in the absence of deleterious cellular effects. We are currently addressing how such an ultra-short electric stimulus is capable of evoking neurosecretion. Preliminary evidence points to a novel mechanism, namely reversible membrane depolarization that depends on the transient formation of sodium-conducting nanopores in the plasma membrane lipid bilayer. That is, a nanoelectropulse causes the plasma membrane lipid bilayer to assume a role typically ascribed to protein ion channels, ion conductance that leads to membrane depolarization. The research spans the disciplines of neurobiology, electrophysiology, biophysics, physics and engineering where experimental approaches, such as patch clamp and fluorescence imaging for monitoring cellular responses, are integrated with electro-physical computational approaches, in particular cell modeling and molecular dynamics simulations that can elucidate on a nanosecond time scale how the electric field interacts with the plasma membrane and how the membrane behaves under the influence of the electric field. Another major goal of the research is to assess further the potential use of nanoelectropulses for modulating neurosecretion by establishing patterns of pulse delivery (pulse number versus pulse rate) that are effective for evoking reproducible effects on catecholamine release without causing adverse effects. The hope is that the research will be critical to the future development of an electrostimulation approach that is less invasive (does not require surgical implantation of electrodes) than the one currently used for neuromodulation, and that it will also result in new strategies for modulating the activity of other types of excitable cells.
- B.S., 1969, Fordham University, Biology
- M.S., 1976, New York University, Pharmacology
- Ph.D., 1982, New York University, Pharmacology
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