Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, USA; Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI, USA.
Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, USA; Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI, USA; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
Exp Neurol. 2020 Sep;331:113381. doi: 10.1016/j.expneurol.2020.113381. Epub 2020 Jun 16.
Spinal cord injury is a severe condition, resulting in specific neurological symptoms depending on the level of damage. Approximately 60% of spinal cord injuries affect the cervical spinal cord, resulting in complete or incomplete tetraplegia and higher mortality rates than injuries of the thoracic or lumbar region. Although cervical spinal cord injuries frequently occur in humans, there are few clinically relevant models of cervical spinal cord injury. Animal models are critical for examining the cellular and molecular manifestations of human cervical spinal cord injury, which is not feasible in the clinical setting, and to develop therapeutic strategies. There is a limited number of studies using cervical, bilateral contusion SCI and providing a behavioral assessment of motor and sensory functions, which is partly due to the high mortality rate and severe impairment observed in severe cervical SCI models. The goal of this study was to develop a mouse model of cervical contusion injury with moderate severity, resulting in an apparent deficit in front and hindlimb function but still allowing for self-care of the animals. In particular, we aimed to characterize a mouse cervical injury model to be able to use genetic models and a wide range of viral techniques to carry out highly mechanistic studies into the cellular and molecular mechanisms of cervical spinal cord injury. After inducing a bilateral, cervical contusion injury at level C5, we followed the recovery of injured and sham-uninjured animals for eight weeks post-surgery. Hindlimb and forelimb motor functions were significantly impaired immediately after injury, and all mice demonstrated partial improvement over time that remained well below that of uninjured control mice. Mice also displayed a significant loss in their sensory function throughout the testing period. This loss of sensory and motor function manifested as a reduced ability to perform skilled motor tasks in all of the injured mice. Here, we describe a new mouse model of moderate bilateral cervical spinal cord injury that does not lead to mortality and provides a comprehensive assessment of histological and behavioral assessments. This model will be useful in enhancing our mechanistic understanding of cervical spinal cord injury and in the development of treatments targeted at promoting neuroprotection, neuroplasticity, and functional recovery after cervical SCI.
脊髓损伤是一种严重的疾病，根据损伤程度会出现特定的神经症状。大约 60%的脊髓损伤影响颈脊髓，导致完全或不完全四肢瘫痪，死亡率高于胸段或腰段损伤。尽管人类经常发生颈脊髓损伤，但临床上相关的颈脊髓损伤模型很少。动物模型对于研究人类颈脊髓损伤的细胞和分子表现至关重要，而这在临床环境中是不可行的，并且可以开发治疗策略。使用颈双侧挫伤性脊髓损伤并提供运动和感觉功能的行为评估的研究很少，这部分是由于严重颈脊髓损伤模型中观察到的高死亡率和严重损伤。本研究的目的是开发一种中度严重程度的颈挫伤损伤小鼠模型，导致前肢和后肢功能明显缺陷，但仍允许动物自我护理。特别是，我们旨在表征一种能够使用遗传模型和广泛的病毒技术来进行颈脊髓损伤的细胞和分子机制的高度机制研究的小鼠颈损伤模型。在 C5 水平诱导双侧颈挫伤损伤后，我们在手术后 8 周内跟踪受伤和假手术未受伤动物的恢复情况。受伤后立即严重损害后肢和前肢运动功能，所有小鼠随着时间的推移均有部分改善，但仍远低于未受伤对照小鼠。在整个测试期间，小鼠的感觉功能也明显丧失。在此期间，感觉和运动功能的丧失表现为所有受伤小鼠进行熟练运动任务的能力降低。在这里，我们描述了一种新的中度双侧颈脊髓损伤小鼠模型，该模型不会导致死亡，并提供全面的组织学和行为评估。该模型将有助于提高我们对颈脊髓损伤的机制理解，并开发针对促进颈脊髓 SCI 后神经保护、神经可塑性和功能恢复的治疗方法。
