Ghnenis Adel B, Jones Calvin, Sefiani Arthur, Douthitt Ashley J, Reyna Andrea J, Rutkowski Joseph M, Geoffroy Cédric G
Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M Health Science Center, Bryan, TX 77807, USA.
Department of Medical Physiology, College of Medicine, Texas A&M Health Science Center, Bryan, TX 77807, USA.
Biology (Basel). 2022 Mar 24;11(4):495. doi: 10.3390/biology11040495.
Changes in cardiometabolic functions contribute to increased morbidity and mortality after chronic spinal cord injury. Despite many advancements in discovering SCI-induced pathologies, the cardiometabolic risks and divergences in severity-related responses have yet to be elucidated. Here, we examined the effects of SCI severity on functional recovery and cardiometabolic functions following moderate (50 kdyn) and severe (75 kdyn) contusions in the thoracic-8 (T8) vertebrae in mice using imaging, morphometric, and molecular analyses. Both severities reduced hindlimbs motor functions, body weight (g), and total body fat (%) at all-time points up to 20 weeks post-injury (PI), while only severe SCI reduced the total body lean (%). Severe SCI increased liver echogenicity starting from 12 weeks PI, with an increase in liver fibrosis in both moderate and severe SCI. Severe SCI mice showed a significant reduction in left ventricular internal diameters and LV volume at 20 weeks PI, associated with increased LV ejection fraction as well as cardiac fibrosis. These cardiometabolic dysfunctions were accompanied by changes in the inflammation profile, varying with the severity of the injury, but not in the lipid profile nor cardiac or hepatic tyrosine hydroxylase innervation changes, suggesting that systemic inflammation may be involved in these SCI-induced health complications.
心脏代谢功能的改变会导致慢性脊髓损伤后发病率和死亡率的增加。尽管在发现脊髓损伤引发的病理变化方面取得了许多进展,但心脏代谢风险以及严重程度相关反应的差异仍有待阐明。在此,我们使用成像、形态测量和分子分析方法,研究了脊髓损伤严重程度对小鼠胸8(T8)椎骨中度(50 千达因)和重度(75 千达因)挫伤后功能恢复和心脏代谢功能的影响。两种严重程度在损伤后 20 周内的所有时间点均降低了后肢运动功能、体重(克)和全身脂肪百分比(%),而只有重度脊髓损伤降低了全身瘦体重百分比(%)。重度脊髓损伤从损伤后 12 周开始增加肝脏回声,中度和重度脊髓损伤均出现肝纤维化增加。重度脊髓损伤小鼠在损伤后 20 周时左心室内径和左心室容积显著减小,同时左心室射血分数增加以及出现心脏纤维化。这些心脏代谢功能障碍伴随着炎症谱的变化,其随损伤严重程度而不同,但血脂谱、心脏或肝脏酪氨酸羟化酶神经支配均无变化,这表明全身炎症可能与这些脊髓损伤引发的健康并发症有关。