Laboratory of Regenertive Neurobiology, Biomedical Center, Department of Neuroscience, Uppsala University, 75124 Uppsala, Sweden.
Cells. 2021 Aug 25;10(9):2185. doi: 10.3390/cells10092185.
Unraveling the cellular and molecular mechanisms of spinal cord injury is fundamental for our possibility to develop successful therapeutic approaches. These approaches need to address the issues of the emergence of a non-permissive environment for axonal growth in the spinal cord, in combination with a failure of injured neurons to mount an effective regeneration program. Experimental in vivo models are of critical importance for exploring the potential clinical relevance of mechanistic findings and therapeutic innovations. However, the highly complex organization of the spinal cord, comprising multiple types of neurons, which form local neural networks, as well as short and long-ranging ascending or descending pathways, complicates detailed dissection of mechanistic processes, as well as identification/verification of therapeutic targets. Inducing different types of dorsal root injury at specific proximo-distal locations provide opportunities to distinguish key components underlying spinal cord regeneration failure. Crushing or cutting the dorsal root allows detailed analysis of the regeneration program of the sensory neurons, as well as of the glial response at the dorsal root-spinal cord interface without direct trauma to the spinal cord. At the same time, a lesion at this interface creates a localized injury of the spinal cord itself, but with an initial neuronal injury affecting only the axons of dorsal root ganglion neurons, and still a glial cell response closely resembling the one seen after direct spinal cord injury. In this review, we provide examples of previous research on dorsal root injury models and how these models can help future exploration of mechanisms and potential therapies for spinal cord injury repair.
解析脊髓损伤的细胞和分子机制对于我们开发成功的治疗方法至关重要。这些方法需要解决脊髓中轴突生长的非许可环境的出现问题，以及受伤神经元无法启动有效再生程序的问题。体内实验模型对于探索机制发现和治疗创新的潜在临床相关性至关重要。然而，脊髓高度复杂的组织，包括多种类型的神经元，它们形成局部神经网络，以及短程和长程的上升或下降通路，使得对机制过程的详细剖析以及治疗靶点的识别/验证变得复杂。在特定的近-远侧位置诱导不同类型的背根损伤为区分脊髓再生失败的关键因素提供了机会。粉碎或切割背根可以对感觉神经元的再生程序以及背根-脊髓界面处的神经胶质反应进行详细分析，而不会对脊髓造成直接创伤。同时，在该界面处造成的损伤是脊髓本身的局部损伤，但初始神经元损伤仅影响背根神经节神经元的轴突，并且仍存在与直接脊髓损伤后所见非常相似的神经胶质细胞反应。在这篇综述中，我们提供了以前关于背根损伤模型的研究示例，以及这些模型如何帮助未来探索脊髓损伤修复的机制和潜在治疗方法。
