Department of Neurological Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY 10065, USA.
Neurotherapeutics. 2011 Oct;8(4):763-73. doi: 10.1007/s13311-011-0058-9.
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.
胚胎内侧神经节隆起（MGE）中的中间神经元祖细胞在移植到出生后皮层后可以迁移、分化并增强局部抑制。移植的 MGE 细胞是否可以减少成年新皮层的癫痫发作活动尚不清楚。我们将来自泛绿色荧光蛋白表达小鼠的活 MGE 或死亡细胞（对照）移植到成年小鼠感觉运动皮层。在移植后 1 周、2 周半或 6 至 8 周，通过在距离移植部位 2 毫米处注射 4-氨基吡啶（4-AP）来诱导急性局灶性癫痫样放电。用 2 个电极记录事件的局部场电位，一个位于 4-AP 焦点，另一个位于移植部位。在所有对照组和活细胞移植的 1 周组中，4-AP 癫痫发作的功率和持续时间从起始部位到移植部位均无衰减。然而，在 MGE 移植后 2.5 或 6 至 8 周，MGE 移植部位的局部场电位功率显着降低，而癫痫发作持续时间几乎没有减少。令人惊讶的是，移植细胞的分布或密度与衰减程度之间没有关系。由于低移植密度仍然显著降低了放电功率，这些数据进一步支持了中间神经元前体细胞移植治疗新皮层癫痫的治疗潜力。
