Tight squeeze, slow burn: inflammation and the aetiology of cervical myelopathy

Abstract

A great deal of progress has been made over the past decade in understanding the role of secondary injury in the progression of brain and spinal cord injury, and the innate immune response has emerged as an important potential therapeutic target (e.g. Beattie, 2004; Donnelly and Popovich, 2008). The microglial response to CNS damage and subsequent invasion of the lesion by peripheral macrophages are associated with the production of pro-inflammatory cytokines and related immune effector molecules that can induce cell death through necrosis and apoptosis both in neurons and oligodendrocytes. Brain and spinal cord injury can initiate a long-lasting cascade of oligodendrocyte death that may lead to chronic demyelination, adding to the dysfunction (e.g. Crowe et al., 1997; Beattie et al., 2002), and this cascade is driven at least in part through the actions of immune mediators including pro-inflammatory cytokines ( Donnelly and Popovich, 2008). Thus, neuroinflammation has been identified as a target for pharmacological therapies, with some evidence of success in animal models of acute spinal cord injury. For example, the anti-inflammatory antibiotic minocycline has been shown to reduce oligodendrocyte apoptosis and spare function in acute cervical spinal cord injury ( Stirling et al., 2004). Neuroinflammation has also been identified as a contributor to cell death in ischaemic stroke and chronic neurodegenerative disorders; and these findings point to the potential commonality of mechanisms underlying cell damage and death in both acute neural injury and slow-developing pathologies like those seen in Alzheimer's; disease and amyotrophic lateral sclerosis. Now, in this issue of Brain, Yu et al. (2011) provide evidence that cervical spondylotic myelopathy, a slow progressive compression injury to the cord and arguably the most prevalent form of spinal cord injury, also involves innate immune responses that contribute to neuronal and oligodendrocyte death, similar to that seen in acute spinal cord injury. Further, they demonstrate that the immunological injury is mediated at least in part by Fas (also known as CD95 or APO-1 receptors) and Fas ligand, components of the immune response known to induce apoptosis. These new results focus attention on the clinical importance of cervical spondylotic myelopathy, and provide a rationale for targeting cell death by pharmacological neuroprotection in addition to treatment by the usual route of surgical decompression (reviewed in Fehlings and Skaf, 1998).