The Belford Center for Spinal Cord Injury, Ohio State University, Columbus, OH, USA; Department of Neuroscience, College of Medicine, Ohio State University, Columbus, OH, USA.
The Belford Center for Spinal Cord Injury, Ohio State University, Columbus, OH, USA; Department of Neurology, Washington University in St. Louis, Missouri, USA.
Exp Neurol. 2021 Aug;342:113725. doi: 10.1016/j.expneurol.2021.113725. Epub 2021 Apr 30.
The current high obesity rates mean that neurological injuries are increasingly sustained on a background of systemic pathology, including liver inflammation, which likely has a negative impact on outcomes. Because obesity involves complex pathology, the effect of hepatic inflammation alone on neurological recovery is unknown. Thus, here we used a gain-of-function model to test if liver inflammation worsens outcome from spinal cord injury (SCI) in rats. Results show liver inflammation concomitant with SCI exacerbated intraspinal pathology and impaired locomotor recovery. Hepatic inflammation also potentiated SCI-induced non-alcoholic steatohepatitis (NASH), endotoxemia and insulin resistance. Circulating and cerebrospinal levels of the liver-derived protein Fetuin-A were higher in SCI rats with liver inflammation, and, when microinjected into intact spinal cords, Fetuin-A caused macrophage activation and neuron loss. Thus, liver inflammation functions as a disease modifying factor to impair recovery from SCI, and Fetuin-A is a potential neuropathological mediator. Since SCI alone induces acute liver inflammation, the liver may be a novel clinical target for improving recovery from SCI.
目前肥胖率居高不下，意味着神经系统损伤越来越多地发生在系统性疾病的背景下，包括肝脏炎症，这可能对结果产生负面影响。由于肥胖涉及复杂的病理，因此单独的肝炎症对神经恢复的影响尚不清楚。因此，在这里我们使用功能获得模型来测试肝脏炎症是否会加重大鼠脊髓损伤（SCI）的预后。结果表明，肝脏炎症伴随 SCI 加重了脊髓内病理学并损害了运动功能恢复。肝脏炎症还增强了 SCI 引起的非酒精性脂肪性肝炎（NASH）、内毒素血症和胰岛素抵抗。SCI 伴有肝脏炎症的大鼠的循环和脑脊液中肝源性蛋白胎球蛋白 A 的水平较高，当将其微注射到完整的脊髓中时，胎球蛋白 A 引起巨噬细胞激活和神经元丢失。因此，肝脏炎症作为一种疾病修饰因子，可损害 SCI 的恢复，胎球蛋白 A 是一种潜在的神经病理学介质。由于单独的 SCI 会引起急性肝炎症，因此肝脏可能是改善 SCI 恢复的新的临床靶标。
