Chen Rui-Yi, Lee Kun-Ze
Department of Biological Sciences, College of Science, National Sun Yat-sen University, Kaohsiung, Taiwan.
Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan.
J Neurotrauma. 2025 Feb;42(3-4):197-211. doi: 10.1089/neu.2024.0342. Epub 2024 Dec 11.
Cervical spinal cord injury usually leads to cardiorespiratory dysfunction due to interruptions of the supraspinal pathways innervating the phrenic motoneurons and thoracic sympathetic preganglionic neurons. Although clinical guidelines recommend maintaining the mean arterial pressure within 85-90 mmHg during the first week of injury, there is no pre-clinical evidence from animal models to prove the therapeutic efficacy of hemodynamic management. Accordingly, the present study was designed to investigate the therapeutic efficacy of hemodynamic management in rats with cervical spinal cord contusion. Adult male rats underwent cervical spinal cord contusion and the implantation of osmotic pumps filled with saline or norepinephrine (NE) (125 μg/(kg·h) for 1 week). The cardiorespiratory function of unanesthetized rats was examined using a non-invasive blood pressure analyzer and double-chamber plethysmography. Cervical spinal cord contusion caused a long-term reduction in the mean arterial pressure and tidal volume. This hypotensive response was significantly reversed in contused rats receiving NE (1 day: 88 ± 19 mmHg; 2 weeks: 96 ± 13 mmHg) compared with contused rats receiving saline (1 day: 72 ± 15 mmHg; 2 weeks: 82 ± 10 mmHg). NE also significantly improved the tidal volume 1 day post-injury (contused + NE: 0.7 ± 0.2 mL; contused + saline: 0.5 ± 0.1 mL). Immunofluorescence staining results revealed that injury-induced reductions of noradrenergic and glutamatergic fibers within the thoracic spinal cord were significantly improved by NE. These results provided the evidence demonstrating that hemodynamic management using NE significantly improves cardiorespiratory function by alleviating neural pathway damage after cervical spinal cord contusion.
颈脊髓损伤通常会导致心肺功能障碍，这是由于支配膈运动神经元和胸段交感神经节前神经元的脊髓上通路中断所致。尽管临床指南建议在损伤后的第一周内将平均动脉压维持在85 - 90 mmHg之间，但尚无来自动物模型的临床前证据来证明血流动力学管理的治疗效果。因此，本研究旨在探讨血流动力学管理对颈脊髓挫伤大鼠的治疗效果。成年雄性大鼠接受颈脊髓挫伤，并植入填充有生理盐水或去甲肾上腺素（NE）（125 μg/(kg·h)，持续1周）的渗透泵。使用无创血压分析仪和双腔体积描记法检查未麻醉大鼠的心肺功能。颈脊髓挫伤导致平均动脉压和潮气量长期降低。与接受生理盐水的挫伤大鼠（1天：72±15 mmHg；2周：82±10 mmHg）相比，接受NE的挫伤大鼠（1天：88±19 mmHg；2周：96±13 mmHg）的这种低血压反应得到了显著逆转。NE还在损伤后1天显著改善了潮气量（挫伤 + NE：0.7±0.2 mL；挫伤 + 生理盐水：0.5±0.1 mL）。免疫荧光染色结果显示，NE显著改善了损伤诱导的胸段脊髓内去甲肾上腺素能和谷氨酸能纤维的减少。这些结果提供了证据，证明使用NE进行血流动力学管理可通过减轻颈脊髓挫伤后的神经通路损伤来显著改善心肺功能。
