Departments of1Neurosurgery and.
2Neurology.
Neurosurg Focus. 2020 Apr 1;48(4):E18. doi: 10.3171/2020.2.FOCUS19955.
Excitatory-inhibitory imbalance is central to epilepsy pathophysiology. Current surgical therapies for epilepsy, such as brain resection, laser ablation, and neurostimulation, target epileptic networks on macroscopic scales, without directly correcting the circuit-level aberrations responsible for seizures. The transplantation of inhibitory cortical interneurons represents a novel neurobiological method for modifying recipient neural circuits in a physiologically corrective manner. Transplanted immature interneurons have been found to disperse in the recipient brain parenchyma, where they develop elaborate structural morphologies, express histochemical markers of mature interneurons, and form functional inhibitory synapses onto recipient neurons. Transplanted interneurons also augment synaptic inhibition and alter recipient neural network synchrony, two physiological processes disrupted in various epilepsies. In rodent models of epilepsy, interneuron transplantation corrects recipient seizure phenotypes and associated behavioral abnormalities. As such, interneuron transplantation may represent a novel neurobiological approach to the surgical treatment of human epilepsy. Here, the authors describe the preclinical basis for applying interneuron transplantation to human epilepsy, discuss its potential clinical applications, and consider the translational hurdles to its development as a surgical therapy.
兴奋性-抑制性失衡是癫痫病理生理学的核心。目前用于治疗癫痫的手术疗法，如脑切除术、激光消融术和神经刺激术，针对的是宏观尺度上的癫痫网络，而没有直接纠正导致癫痫发作的回路水平异常。抑制性皮质中间神经元的移植代表了一种新颖的神经生物学方法，可以以生理矫正的方式修饰受者的神经回路。已经发现移植的不成熟中间神经元在受者脑实质中分散，在那里它们发展出精细的结构形态，表达成熟中间神经元的组织化学标志物，并形成功能性抑制性突触到受者神经元上。移植的中间神经元还增强了突触抑制并改变了受者神经网络的同步性，这两个生理过程在各种癫痫中都被打乱了。在癫痫的啮齿动物模型中，中间神经元移植纠正了受者的癫痫表型和相关的行为异常。因此，中间神经元移植可能代表了一种治疗人类癫痫的新的神经生物学方法。在这里，作者描述了将中间神经元移植应用于人类癫痫的临床前基础，讨论了其潜在的临床应用，并考虑了将其发展为手术治疗的转化障碍。
