The Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
Exp Neurol. 2010 Feb;221(2):346-52. doi: 10.1016/j.expneurol.2009.12.004. Epub 2009 Dec 11.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease where motor neurons within the brain and spinal cord are lost, leading to paralysis and death. Recently, a correlation between head trauma and the incidence of ALS has been reported. Furthermore, new invasive neurosurgical studies are being planned which involve inserting needles directly to the spinal cord. We therefore tested whether acute trauma to the spinal cord via a knife wound injury would lead to accelerated disease progression in rodent models of ALS (SOD1(G93A) rats). A longitudinal stab injury using a small knife was performed within the lumbar spinal cord region of presymptomatic SOD1(G93A) rats. Host glial activation was detected in the lumbar area surrounding a micro-knife lesion at 2 weeks after surgery in both wild type and SOD1(G93A) animals. However, there was no sign of motor neuron loss in the injured spinal cord of any animal and normal motor function was maintained in the ipsilateral limb. These results indicate that motor neurons in presymptomatic G93A animals are not affected by an invasive puncture wound injury involving reactive astrocytes. Furthermore, acute trauma alone does not accelerate disease onset or progression in this ALS model which is important for future strategies of gene and cell therapies directly targeting the spinal cord of ALS patients.
肌萎缩侧索硬化症（ALS）是一种神经退行性疾病，大脑和脊髓中的运动神经元会逐渐丧失，导致瘫痪和死亡。最近，有报道称头部外伤与 ALS 的发病率之间存在相关性。此外，还计划进行新的侵袭性神经外科研究，其中包括将针直接插入脊髓。因此，我们测试了通过刀伤对脊髓造成急性创伤是否会导致 ALS 啮齿动物模型（SOD1（G93A）大鼠）的疾病进展加速。在 SOD1（G93A）大鼠出现症状前，在腰椎脊髓区域进行了小 knife 的纵向刺伤。在手术 2 周后，在野生型和 SOD1（G93A）动物的腰椎区域均检测到宿主神经胶质细胞的激活。然而，任何动物的受伤脊髓中均没有运动神经元丢失的迹象，并且对侧肢体的运动功能保持正常。这些结果表明，涉及反应性星形胶质细胞的侵袭性穿刺伤不会影响无症状 G93A 动物中的运动神经元。此外，在该 ALS 模型中，急性创伤本身不会加速疾病的发作或进展，这对于直接针对 ALS 患者脊髓的基因和细胞治疗的未来策略非常重要。
