A Swine Model of Neural Circuit Electromagnetic Fields: Effects of Immediate Electromagnetic Field Stimulation on Cortical Injury.

Background Neurologic diseases have profound disability, mortality, and socioeconomic effects worldwide. Treatment of these disorders varies but is largely limited to unique factors associated with neural physiology. Early studies have evaluated alterations in electromagnetic fields (EMF) due to neural disorders with subsequent modulation of EMF as a potential treatment modality. Swine models have begun to be evaluated as translational models in this effect. Methods EMF measurements of a Yucatan miniswine were recorded using proprietary non-contact, non-invasive induction sensors with a dual layer Mu-metal and interlaced copper mesh helmet. The swine then underwent controlled cortical impact (CCI) to simulate traumatic brain injury (TBI). Twenty minutes post-injury after surgical wound closure, the swine underwent targeted EMF signal modulation using a signal generator to stimulate the swine's injured cortical circuit using a sinusoidal wave individualized at 2.5 Hz with a 500mV positive offset at 1V. After 10 days of stimulation, settings were modified to another individualized frequency of 5.5 Hz, 500mV positive offset and 1V for stimulation. Behavioral patterns in swine were evaluated, and EMF measurements were recorded daily prior to, during, and after stimulation. Artificial intelligence (AI) models evaluated patterns in EMF signals. Histology of the stimulated swine cortex was evaluated using hematoxylin and eosin staining and pentachrome staining and compared to a control swine without stimulation and a swine that had received stimulation two days post-injury in a delayed fashion. Serial serum specimens and tissue at the time of euthanasia were obtained for assessment of neuron-specific enolase (NSE) concentration. Results Pre-operative and post-stimulation measurements demonstrated differences in patterns and activity early on. There was an identified peak at 1.6Hz, not frequently seen pre-operatively. There were convergent frequencies in both data sets at 10.5 Hz and 3.9 Hz. Plateaus and decreased variability of changes in slope were identified early in the post-injury phase. AI modeling identified early similarities in pre-operative and post-stimulation measurements through the patterns of peaks with similarities on postoperative day 10 and similarities in the valleys on postoperative day 17. Histologic specimens identified increased degrees of apoptosis and cellular death in the non-stimulated control compared to the stimulated swine. Similarly, the immediately stimulated swine had less apoptosis and increased histologic viability at the site of injury compared to the two-day delayed stimulation swine. There were increased levels of NSE noted in the stimulated swine at the site of injury compared to non-injured sites and the control swine. Conclusions Cortical function was appropriately measured through induction sensors and shielding in the form of a helmet and electromagnetic field channels. Early stimulation resulted in the early and durable recovery of neuronal circuit-driven electromagnetic field patterns. Histology identified increased viability of neurons with fewer apoptotic neurons and glial cells in stimulated swine with early stimulation identifying the best effect compared to a non-stimulated subject. This recovery identifies change and recovery at the circuit, cellular, and subcellular levels that potentiate the need for further study of EMF modulation as a treatment modality in neurological disorders.