Abstracts

Rationale: Multipotent progenitor cells have great potential in the treatment of neurological diseases such as epilepsy. Interneuron progenitors from the embryonic medial ganglionic eminence (MGE) can survive, migrate, and differentiate into GABAergic interneurons after transplantation into adult brain. Whether grafted MGE cells can reduced epileptic activity is unknown. Methods: We transplanted dorsal MGE (dMGE), ventral MGE (vMGE) and killed cells (control) from GFP mice) into adult mouse neocortex. Seven weeks after transplant, acute focal ictal discharges were induced by injection of 4-aminopyridine (4-AP, 15mM, 0.5 μl) 2 mm away from the site of transplantation. The local field potential (LFP) of the seizures was recorded with two electrodes, one located in the 4-AP focus and the other in the transplantation site. Results: A total of 248 ictal discharges was recorded in 13 mice. In the control group, 4-AP seizures revealed no attenuation in power and duration from the onset site to the site of transplantation (p>0.05, n=3 mice, 38 seizures). Following dMGE and vMGE transplant, there was no difference in the duration of seizures between the injection site and the site of transplantation. LFP power, however, decreased from 3552.5 ±1076.3 mV2 to 723.7±566.0 mV2 in dMGE transplanted site (p< 0.01, n=5 mice, 85 seizures), and from 11376.0 ± 2504.3 mV2 to 1965.0±834.8 mV2 in the vMGE transplanted site (P<0.001, n=5 mice, 125 seizures). Preliminary analyses suggest a positive effect of graft distribution and density on the degree of seizure attenuation. Conclusions: These data demonstrate that MGE progenitor cell transplantation attenuates seizure propagation and may provide potential therapeutic option in the treatment of neocortical epilepsy.