Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
Department of Orthopedic Surgery, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan.
J Appl Physiol (1985). 2023 Dec 1;135(6):1268-1283. doi: 10.1152/japplphysiol.00473.2023. Epub 2023 Oct 19.
Cervical spinal cord injury interrupts supraspinal pathways innervating thoracic sympathetic preganglionic neurons and results in cardiovascular dysfunction. Both respiratory and locomotor functions were also impaired due to damages of motoneuron pools controlling respiratory and forelimb muscles, respectively. However, no study has investigated autonomic and somatic motor functions in the same animal model. The present study aimed to establish a cervical spinal cord injury model to evaluate cardiorespiratory response and locomotor activity in unanesthetized rats. Cardiovascular response and respiratory behavior following laminectomy or cervical spinal contusion were measured using noninvasive blood pressure analyzer and plethysmography systems, respectively. Locomotor activity was evaluated by an open-field test and a locomotor rating scale. The results demonstrated that mean arterial blood pressure and heart rate were significantly reduced in contused rats compared with uninjured rats at the acute injured stage. Tidal volume was also significantly reduced during the acute and subchronic stages. Moreover, locomotor function was severely impaired, evidenced by decreasing moving ability and locomotor rating scores from the acute to chronic injured stages. Retrograde neurotracer results revealed that cervical spinal cord injury caused a reduction in number of phrenic and triceps motoneurons. Immunofluorescence staining revealed a significant attenuation of serotonergic, noradrenergic, glutamatergic, and GABAergic fibers innervating the thoracic sympathetic preganglionic neurons in chronically contused rats. These results revealed the pathological mechanism underlying the comorbidity of cardiorespiratory and locomotor dysfunction following cervical spinal cord injury. We proposed that this animal model can be used to evaluate the therapeutic efficacy of potential strategies to improve different physiological functions. The present study establishes a preclinical rodent model to comprehensively investigate physiological functions under unanesthetized condition following cervical spinal cord contusion. The results demonstrated that cervical spinal cord contusion is associated with impairments in cardiovascular, respiratory, and locomotor function. Respiratory and forelimb motoneurons and neurochemical innervations of sympathetic preganglionic neurons were damaged following injury. This animal model can be used to evaluate the therapeutic efficacy of potential strategies to improve different physiological functions.
颈椎脊髓损伤中断了胸交感节前神经元的上位通路，导致心血管功能障碍。呼吸和运动功能也受到损害，分别是由于控制呼吸和前肢肌肉的运动神经元池受损。然而，没有研究在同一动物模型中调查自主和躯体运动功能。本研究旨在建立颈椎脊髓损伤模型，以评估未麻醉大鼠的心肺反应和运动活动。使用无创血压分析仪和 plethysmography 系统分别测量椎板切除术或颈椎脊髓挫伤后的心血管反应和呼吸行为。通过旷场试验和运动评分量表评估运动活动。结果表明，与未受伤大鼠相比，挫伤大鼠在急性受伤阶段的平均动脉血压和心率明显降低。潮气量在急性和亚慢性阶段也明显减少。此外，运动功能严重受损，表现为从急性到慢性受伤阶段，移动能力和运动评分降低。逆行神经示踪结果表明，颈椎脊髓损伤导致膈神经和三头肌运动神经元数量减少。免疫荧光染色显示，慢性挫伤大鼠胸交感节前神经元支配的 5-羟色胺能、去甲肾上腺素能、谷氨酸能和 GABA 能纤维明显减弱。这些结果揭示了颈椎脊髓损伤后心肺和运动功能障碍共病的病理机制。我们提出，这种动物模型可用于评估潜在策略治疗改善不同生理功能的疗效。本研究建立了一种未经麻醉的颈椎脊髓挫伤后在啮齿动物模型中全面研究生理功能的临床前模型。结果表明，颈椎脊髓挫伤与心血管、呼吸和运动功能障碍有关。损伤后，呼吸和前肢运动神经元以及交感节前神经元的神经化学传入纤维受损。这种动物模型可用于评估潜在策略治疗改善不同生理功能的疗效。
