Dept. Physical Therapy, College of Public Health and Health Professions, McKnight Brain Institute, University of Florida, USA.
Dept. of Biomedical Engineering, College of Engineering, University of Miami, USA.
Exp Neurol. 2014 Jan;251:47-57. doi: 10.1016/j.expneurol.2013.10.016. Epub 2013 Nov 2.
Rat fetal spinal cord (FSC) tissue, naturally enriched with interneuronal progenitors, was introduced into high cervical, hemi-resection (Hx) lesions. Electrophysiological analyses were conducted to determine if such grafts exhibit physiologically-patterned neuronal activity and if stimuli which increase respiratory motor output also alter donor neuron bursting. Three months following transplantation, the bursting activity of FSC neurons and the contralateral phrenic nerve were recorded in anesthetized rats during a normoxic baseline period and brief respiratory challenges. Spontaneous neuronal activity was detected in 80% of the FSC transplants, and autocorrelation of action potential spikes revealed distinct correlogram peaks in 87% of neurons. At baseline, the average discharge frequency of graft neurons was 13.0 ± 1.7 Hz, and discharge frequency increased during a hypoxic respiratory challenge (p<0.001). Parallel studies in unanesthetized rats showed that FSC tissue recipients had larger inspiratory tidal volumes during brief hypoxic exposures (p<0.05 vs. C2Hx rats). Anatomical connectivity was explored in additional graft recipients by injecting a transsynaptic retrograde viral tracer (pseudorabies virus, PRV) directly into matured transplants. Neuronal labeling occurred throughout graft tissues and also in the host spinal cord and brainstem nuclei, including those associated with respiratory control. These results underscore the neuroplastic potential of host-graft interactions and training approaches to enhance functional integration within targeted spinal circuitry.
大鼠胎脊髓（FSC）组织自然富含中间神经元祖细胞，被引入高颈段半切（Hx）损伤。进行电生理分析以确定此类移植物是否表现出具有生理模式的神经元活动，以及是否刺激增加呼吸运动输出也会改变供体神经元爆发。移植后 3 个月，在麻醉大鼠中记录了 FSC 神经元和对侧膈神经在正常氧基线期和短暂呼吸挑战期间的爆发活动。在 80%的 FSC 移植中检测到自发神经元活动，并且在 87%的神经元中自相关动作电位尖峰显示出明显的相关图峰。在基线时，移植物神经元的平均放电频率为 13.0±1.7 Hz，并且在缺氧呼吸挑战期间放电频率增加（p<0.001）。在未麻醉大鼠中的平行研究表明，FSC 组织接受者在短暂缺氧暴露期间具有更大的吸气潮气量（p<0.05 与 C2Hx 大鼠相比）。在其他移植物接受者中通过将突触逆行病毒示踪剂（伪狂犬病病毒，PRV）直接注射到成熟移植物中探索了解剖学连接。神经元标记发生在整个移植物组织中，也发生在宿主脊髓和脑干核中，包括与呼吸控制相关的核。这些结果强调了宿主-移植物相互作用的神经可塑性潜力和培训方法，以增强靶向脊髓电路内的功能整合。
