Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia; Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia.
Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia.
Bone. 2020 Apr;133:115263. doi: 10.1016/j.bone.2020.115263. Epub 2020 Feb 4.
Neurological heterotopic ossification (NHO) is characterized by abnormal bone growth in soft tissue and joints in response to injury to the central nervous system. The ectopic bone frequently causes pain, restricts mobility, and decreases the quality of life for those affected. NHO commonly develops in severe traumatic brain injury (TBI) patients, particularly in the presence of concomitant musculoskeletal injuries (i.e. polytrauma). There are currently no animal models that accurately mimic these combinations of injuries, which has limited our understanding of NHO pathobiology, as well as the development of biomarkers and treatments, in TBI patients. In order to address this shortcoming, here we present a novel rat model that combines TBI, femoral fracture, and muscle crush injury. Young adult male Sprague Dawley rats were randomly assigned into three different injury groups: triple sham-injury, peripheral injury only (i.e., sham-TBI + fracture + muscle injury) or triple injury (i.e., TBI + fracture + muscle injury). Evidence of ectopic bone in the injured hind-limb, as confirmed by micro-computed tomography (μCT), was found at 6-weeks post-injury in 70% of triple injury rats, 20% of peripheral injury rats, and 0% of the sham-injured controls. Furthermore, the triple injury rats had higher ectopic bone severity scores than the sham-injured group. This novel model will provide a platform for future studies to identify underlying mechanisms, biomarkers, and develop evidence based pharmacological treatments to combat this debilitating long-term complication of TBI and polytrauma.
神经异位骨化（NHO）的特征是中枢神经系统损伤后软组织和关节异常骨生长。异位骨常引起疼痛，限制活动，并降低受影响者的生活质量。NHO 通常在严重创伤性脑损伤（TBI）患者中发展，特别是在伴有肌肉骨骼损伤（即多发伤）的情况下。目前尚无准确模拟这些损伤组合的动物模型，这限制了我们对 TBI 患者 NHO 病理生物学的理解，以及生物标志物和治疗方法的发展。为了解决这一不足，我们在这里提出了一种新的大鼠模型，该模型结合了 TBI、股骨骨折和肌肉挤压伤。年轻成年雄性 Sprague Dawley 大鼠被随机分为三组不同的损伤组：三重假损伤组、外周损伤组（即 sham-TBI+骨折+肌肉损伤）或三重损伤组（即 TBI+骨折+肌肉损伤）。受伤后 6 周，通过微计算机断层扫描（μCT）证实，70%的三重损伤大鼠、20%的外周损伤大鼠和 0%的假损伤对照大鼠的受伤后肢出现异位骨。此外，三重损伤大鼠的异位骨严重程度评分高于假损伤组。这种新模型将为未来的研究提供一个平台，以确定潜在的机制、生物标志物，并开发基于证据的药理学治疗方法，以对抗 TBI 和多发伤的这种衰弱的长期并发症。
