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In this chapter, the authors explore the role of the various “players” that characterize the inflammatory milieu with specific focus on neurological disorders pertaining to the sphere of neuro-oncology and neuro-traumatology. Tumor necrosis factor-a (TNF-a) is a known potent inflammatory mediator, playing a key role in the inflammatory milieu. Specifically, TNF-a is a major player in coordinating recruitment of other inflammatory cells and mediators. In vitro evidence that whenever microglia regulation is altered pre-cancerous conditions may develop supports the theories behind a correlation between inflammatory milieu and gliomas as well as other central nervous system malignancies. Finding the precise link between immunological response to inflammation and the continuous amplification of the pathological circle leading to chronic diseases will certainly provide us with tremendous opportunities to design …