Rationale: Severity, expressed as the percentage of mice with clonic activity, and lethality of seizures increase with the dose of NMDA given intracerebroventicularly (icv). We have reported partial protection by certain DC electromagnetic fields against the clonic phase of seizures produced by a non-lethal dose of NMDA (Soc Neurosci Abs 21:1517, 1995). Here we have explored the efficacy of the field against different doses of NMDA.
Methods: Intracerebroventricular (icv) injection of NMDA in mice produced brief (<5 min) seizures including clonic manifestations (CLO). For comparison with concomitant controls, other mice (MAG) were pretreated with a DC magnetic field produced by an array of four electromagnets (60 milliTesla field at center of cores) of alternating polarity. Mice in bottles were placed in gradient regions of the field for 15 minutes prior to icv NMDA.
Results: The percentage of mice manifesting the CLO stage varied with NMDA dose (in nanomoles): 0.75-1.15 = 40% in controls, 12% in MAG mice; 1.2-1.5 = 70% in controls, 30% in MAG mice; 25 = 60% and 40% deaths in controls and 80% CLO and deaths in MAG mice. Protection against the two lowest doses was significant (p<0.01). Gradual heating of the cores was associated with worsened seizures only in mice given the highest NMDA dose.
Conclusions: Protective efficacy of the DC magnetic field is best at the threshold for seizure production and can be overcome by NMDA doses that are lethal in a large percentage of mice. Improved outcome may occur with electromagnets of different design.
[Supported by a collaborative arrangement between the Holcomb Medical Research Institute, Vanderbilt University and MJM.]