title: Interneuron progenitors attenuate the power of acute focal ictal discharges.
abstract: Interneuron progenitors from the embryonic medial ganglionic eminence (MGE) can migrate, differentiate, and enhance local inhibition after transplantation into the postnatal cortex. Whether grafted MGE cells can reduce ictal activity in adult neocortex is unknown. We transplanted live MGE or killed cells (control) from pan green fluorescent protein expressing mice into adult mouse sensorimotor cortex. One week, 2 and 1/2 weeks, or 6 to 8 weeks after transplant, acute focal ictal epileptiform discharges were induced by injection of 4-aminopyridine (4-AP) 2 mm away from the site of transplantation. The local field potential of the events was recorded with 2 electrodes, 1 located in the 4-AP focus and the other 1 in the transplantation site. In all control groups and in the 1-week live cell transplant, 4-AP ictal discharges revealed no attenuation in power and duration from the onset site to the site of transplantation. However, 2.5 or 6 ~ 8 weeks after MGE transplants, there was a dramatic decrease in local field potential power at the MGE transplanted site with little decrease in ictal duration. Surprisingly, there was no relationship between grafted cell distribution or density and the degree of attenuation. As remarkably low graft densities still significantly reduced discharge power, these data provide further support for the therapeutic potential of interneuron precursor transplants in the treatment of neocortical epilepsy.
authors: Department of Neurological Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY 10065, USA.
authors: Estanislao
authors: E
authors: De la Cruz
authors: Mingrui
authors: M
authors: Zhao
authors: Lihua
authors: L
authors: Guo
authors: Hongtao
authors: H
authors: Ma
authors: Stewart A
authors: SA
authors: Anderson
authors: Theodore H
authors: TH
authors: Schwartz
mesh_terms: D015761:4-Aminopyridine / Q000633:toxicity; D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002135:Calcium-Binding Proteins; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000502:physiology; D004827:Epilepsy / Q000139:chemically induced / Q000601:surgery*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007395:Interneurons / Q000502:physiology*; D019394:Ki-67 Antigen / Q000378:metabolism; D008124:Locomotion / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins; D019579:Neocortex / Q000166:cytology* / Q000601:surgery; D009419:Nerve Tissue Proteins / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000633:toxicity; D016548:Prosencephalon / Q000166:cytology / Q000502:physiology / Q000637:transplantation; D011930:Reaction Time; D013997:Time Factors
chemical_list: C112986:AIF1 protein, human; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D026902:Potassium Channel Blockers; D049452:Green Fluorescent Proteins; D015761:4-Aminopyridine