Neuroinflammation, the thread connecting neurological disease

Excerpt

The term neuroinflammation broadly identifies the response of the central nervous system (CNS) to injury and disease. It encompasses cascades initiated by the coordinated action of neural and non-neural cells, all directed towards the ultimate goal of protecting the CNS and preserving its integrity. Because of its complexity and multifactorial nature, it is easy to understand why even a minimal unbalance in any of its components may result in unwanted consequences that hinder CNS recovery, rather than promoting it. Since this maladaptive outcome often prevails, the term neuroinflammation has, over time, taken a negative connotation. However, in recent years, partly due to the failure of highly anticipated clinical trials targeting presumptive pro-inflammatory neurotoxic molecules (e.g., the lenercept trial with a TNF inhibitor for multiple sclerosis [1]), it has become apparent that this one-sided view of the neuroinflammatory process is rather restrictive, if not inaccurate. In vivo studies using gene-targeting approaches and next-generation transcriptomics have uncovered that abolishing or inhibiting signals long considered as the prototypical drivers of neuroinflammation did not necessarily result in CNS protection. On the contrary, it occasionally led to exacerbation of the damage [2, 3]. This has fueled a renewed interest in the field, with a flurry of studies investigating the mechanisms underlying the neuroinflammatory process from different perspectives. What we learned is that the same cascade/molecule may be detrimental or protective to CNS recovery depending upon time and place of action, as well as the cellular source it derives from. Furthermore, the same cell population can adapt its function to the composition of the surrounding environment, thereby sustaining or suppressing the neuroinflammatory response. Given the multiple factors and pathways involved in this process, as well as its various manifestations, some have suggested that the use of the term neuroinflammation may need to be revisited because it is misrepresentative of the pathology of certain CNS disorders [4]. …