Department of Clinical Neurosciences, Anne McLaren Laboratory, Wellcome Trust-MRC Cambridge Stem Cell Institute, John van Geest Centre for Brain Repair, Academic Neurosurgery Unit, University of Cambridge, Cambridge Biomedical Campus, West Forvie Building, Forvie Site, Robinson Way, Cambridge, CB2 0SZ, UK.
Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Clifford Allbutt Building, Cambridge Biomedical Campus, Cambridge, CB2 0AH, UK.
Acta Neuropathol Commun. 2016 Aug 23;4(1):89. doi: 10.1186/s40478-016-0359-7.
Cervical spondylotic myelopathy (CSM) is the most common spinal cord disorder and a major cause of disability in adults. Improvements following surgical decompression are limited and patients often remain severely disabled. Post mortem studies indicate that CSM is associated with profound axonal loss. However, our understanding of the pathophysiology of CSM remains limited.To investigate the hypothesis that axonal plasticity plays a role in the recovery following surgical decompression, we adopted a novel preclinical model of mild to moderate CSM. Spinal cord compression resulted in significant locomotor deterioration, increased expression of the axonal injury marker APP, and loss of serotonergic fibres. Surgical decompression partially reversed the deficits and attenuated APP expression. Decompression was also associated with axonal sprouting, reflected in the restoration of serotonergic fibres and an increase of GAP43 expression. The re-expression of synaptophysin indicated the restoration of functional synapses following decompression. Promoting axonal plasticity may therefore be a therapeutic strategy for promoting neurological recovery in CSM.
颈椎脊髓病(CSM)是最常见的脊髓疾病,也是成年人残疾的主要原因。手术减压后的改善是有限的,患者往往仍然严重残疾。尸检研究表明,CSM 与严重的轴突丢失有关。然而,我们对 CSM 的病理生理学的理解仍然有限。为了研究轴突可塑性在手术减压后恢复中起作用的假设,我们采用了一种新的轻度至中度 CSM 的临床前模型。脊髓压迫导致运动功能显著恶化,轴突损伤标志物 APP 的表达增加,以及 5-羟色胺能纤维丢失。手术减压部分逆转了这些缺陷,并减弱了 APP 的表达。减压还与轴突发芽有关,反映在 5-羟色胺能纤维的恢复和 GAP43 表达的增加。突触素的重新表达表明,减压后功能突触的恢复。因此,促进轴突可塑性可能是促进 CSM 神经恢复的一种治疗策略。