Huffman Emily E, Dong Brittany E, Clarke Harrison A, Young Lyndsay E A, Gentry Matthew S, Allison Derek B, Sun Ramon C, Waters Christopher M, Alilain Warren J
Department of Neuroscience, University of Kentucky College of Medicine, Lexington, KY 40508, USA.
Spinal Cord and Brain Injury Research Center, University of Kentucky College of Medicine, Lexington, KY 40508, USA.
Brain Commun. 2023 Mar 28;5(2):fcad091. doi: 10.1093/braincomms/fcad091. eCollection 2023.
High-cervical spinal cord injury often disrupts respiratory motor pathways and disables breathing in the affected population. Moreover, cervically injured individuals are at risk for developing acute lung injury, which predicts substantial mortality rates. While the correlation between acute lung injury and spinal cord injury has been found in the clinical setting, the field lacks an animal model to interrogate the fundamental biology of this relationship. To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury = 18 alongside sham injury ( = 3) and naïve animals ( = 15) to assess lung injury in adult rats. We demonstrate that animals display some early signs of lung injury two weeks post-spinal cord injury. While no obvious histological signs of injury were observed, the spinal cord injured cohort displayed significant signs of metabolic dysregulation in multiple pathways that include amino acid metabolism, lipid metabolism, and N-linked glycosylation. Collectively, we establish for the first time a model of lung injury after spinal cord injury at an acute time point that can be used to monitor the progression of lung damage, as well as identify potential targets to ameliorate acute lung injury.
高位颈髓损伤常常会破坏呼吸运动通路，导致受影响人群呼吸功能丧失。此外，颈部受伤的个体有发生急性肺损伤的风险，这预示着相当高的死亡率。虽然在临床环境中已发现急性肺损伤与脊髓损伤之间存在关联，但该领域缺乏一种动物模型来探究这种关系的基础生物学机制。为了开始填补这一知识空白，我们对18只成年大鼠进行了实验性颈髓损伤，并设置了3只假手术组动物和15只未受伤的动物作为对照，以评估肺损伤情况。我们证明，脊髓损伤两周后，动物出现了一些肺损伤的早期迹象。虽然未观察到明显的组织学损伤迹象，但脊髓损伤组在包括氨基酸代谢、脂质代谢和N-糖基化在内的多个途径中显示出明显的代谢失调迹象。总体而言，我们首次建立了脊髓损伤后急性时间点的肺损伤模型，该模型可用于监测肺损伤的进展，并确定改善急性肺损伤的潜在靶点。
