Hsu Shih-Hui, Lee Kun-Ze
Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan;
Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Center for Neuroscience, National Sun Yat-sen University, Kaohsiung, Taiwan; Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan; and Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung, Taiwan
J Appl Physiol (1985). 2015 Nov 15;119(10):1075-87. doi: 10.1152/japplphysiol.00329.2015. Epub 2015 Sep 10.
Unilateral cervical spinal cord hemisection (i.e., C2Hx) usually interrupts the bulbospinal respiratory pathways and results in respiratory impairment. It has been demonstrated that activation of the serotonin system can promote locomotor recovery after spinal cord injury. The present study was designed to investigate whether serotonergic activation can improve respiratory function during the chronic injury state. Bilateral diaphragm electromyogram and tidal volume were measured in anesthetized and spontaneously breathing adult rats at 8 wk post-C2Hx or C2 laminectomy. A bolus intravenous injection of a serotonin precursor [5-hydroxytryptophan (5-HTP), 10 mg/kg], a serotonin reuptake inhibitor (fluoxetine, 10 mg/kg), or a potent agonist for serotonin 2A receptors (TCB-2, 0.05 mg/kg) was used to activate the serotonergic system. Present results demonstrated that 5-HTP and TCB-2, but not fluoxetine, significantly increased the inspiratory activity of the diaphragm electromyogram ipsilateral to the lesion for at least 30 min in C2Hx animals, but not in animals that received sham surgery. However, the tidal volume was not increased after administration of 5-HTP or TCB-2, indicating that the enhancement of ipsilateral diaphragm activity is not associated with improvement of the tidal volume. These results suggest that exogenous activation of the serotonergic system can specifically enhance the ipsilateral diaphragmatic motor outputs, but this approach may not be sufficient to improve respiratory functional recovery following chronic cervical spinal injury.
单侧颈脊髓半横断（即C2Hx）通常会中断延髓脊髓呼吸通路并导致呼吸功能受损。已有研究表明，5-羟色胺系统的激活可促进脊髓损伤后的运动功能恢复。本研究旨在探讨5-羟色胺能激活在慢性损伤状态下是否能改善呼吸功能。在C2Hx或C2椎板切除术后8周，对麻醉状态下自主呼吸的成年大鼠测量双侧膈肌肌电图和潮气量。通过静脉推注5-羟色胺前体[5-羟色氨酸（5-HTP），10mg/kg]、5-羟色胺再摄取抑制剂（氟西汀，10mg/kg）或5-羟色胺2A受体强效激动剂（TCB-2，0.05mg/kg）来激活5-羟色胺能系统。目前的结果表明，在C2Hx动物中，5-HTP和TCB-2能显著增加损伤侧同侧膈肌肌电图的吸气活动至少30分钟，但在接受假手术的动物中则无此现象。然而，给予5-HTP或TCB-2后潮气量并未增加，这表明同侧膈肌活动的增强与潮气量的改善无关。这些结果表明，5-羟色胺能系统的外源性激活可特异性增强同侧膈肌运动输出，但这种方法可能不足以改善慢性颈脊髓损伤后的呼吸功能恢复。
