Lin Chia-Ching, Lai Sih-Rong, Shao Yu-Han, Chen Chun-Lin, Lee Kun-Ze
Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung, Taiwan.
Neurotherapeutics. 2017 Jul;14(3):792-809. doi: 10.1007/s13311-016-0509-4.
Respiratory impairment due to damage of the spinal respiratory motoneurons and interruption of the descending drives from brainstem premotor neurons to spinal respiratory motoneurons is the leading cause of morbidity and mortality following cervical spinal cord injury. The present study was designed to evaluate the therapeutic effectiveness of delayed transplantation of fetal spinal cord (FSC) tissue on respiratory function in rats with mid-cervical spinal cord injury. Embryonic day-14 rat FSC tissue was transplanted into a C4 spinal cord hemilesion cavity in adult male rats at 1 week postinjury. The histological results showed that FSC-derived grafts can survive, fill the lesion cavity, and differentiate into neurons and astrocytes at 8 weeks post-transplantation. Some FSC-derived graft neurons exhibited specific neurochemical markers of neurotransmitter (e.g., serotonin, noradrenalin, or acetylcholine). Moreover, a robust expression of glutamatergic and γ-aminobutyric acid-ergic fibers was observed within FSC-derived grafts. Retrograde tracing results indicated that there was a connection between FSC-derived grafts and host phrenic nucleus. Neurophysiological recording of the phrenic nerve demonstrated that phrenic burst amplitude ipsilateral to the lesion was significantly greater in injured animals that received FSC transplantation than in those that received buffer transplantation under high respiratory drives. These results suggest that delayed FSC transplantation may have the potential to repair the injured spinal cord and promote respiratory functional recovery after mid-cervical spinal cord injury.
脊髓呼吸运动神经元受损以及脑干运动前神经元至脊髓呼吸运动神经元的下行驱动中断所导致的呼吸功能障碍，是颈脊髓损伤后发病和死亡的主要原因。本研究旨在评估延迟移植胎儿脊髓（FSC）组织对颈段脊髓中段损伤大鼠呼吸功能的治疗效果。在成年雄性大鼠损伤后1周，将胚胎第14天的大鼠FSC组织移植到C4脊髓半切损伤腔内。组织学结果显示，移植后8周，FSC来源的移植物能够存活、填充损伤腔，并分化为神经元和星形胶质细胞。一些FSC来源的移植物神经元表现出神经递质的特定神经化学标记（如5-羟色胺、去甲肾上腺素或乙酰胆碱）。此外，在FSC来源的移植物内观察到谷氨酸能和γ-氨基丁酸能纤维的强烈表达。逆行追踪结果表明，FSC来源的移植物与宿主膈神经核之间存在联系。膈神经的神经生理学记录表明，在高呼吸驱动下，接受FSC移植的损伤动物损伤侧的膈神经爆发幅度明显大于接受缓冲液移植的动物。这些结果表明，延迟FSC移植可能具有修复损伤脊髓并促进颈段脊髓中段损伤后呼吸功能恢复的潜力。
