Joo O Malva and Catarina R Oliveira

Evidence exists showing a clear interaction between neurons, glia, and cells of the immune system, which is highly dynamic and highly regulated, playing a key role in brain homeostasis. There is increasing support for the contribution of the disruption of this interaction to the inflammatory (neuroinflammatory) and immune (neuroimmunity) responses associated to many diseases of the nervous system. In the present section, the major molecular and cellular players in neuroinflammation are introduced and their role in neuronal death/protection and brain repair is discussed.

In Chap. 1, Bernardino and Malva introduce neuroimmunity and neuro inflammation in health and disease, highlighting the close interaction between the innate immune response and excito toxicity. The key proinflammatory cytokines, chemokines, receptors, and mechanisms involved in IL-ip and TNF-a receptors-mediated signaling transduction are reviewed. The central role of microglia activation in the innate immune response of the brain and its impact in neuronal death/survival is discussed. The authors introduce in this chapter many of the recurrent concepts used in other sections/chapters of the book.

In Chap. 2, by Bente Finsen's group (Wirenfeldt et al.,) the authors revise and discuss the developmental origin and diversity of microglial cells and their response to injury. The highly dynamic plasticity of microglial populations in response to injury is explored and deeply discussed. The readers are invited to understand microglial diversity as a natural resource of brain development and defence against aggression.

Chapter 3 by Cunha, Chen, and Sitkovsky discuss the role of ATP in brain and peripheral response to injury. The shortcut between protection and toxicity and the ambiguous role of adenosine and adenosine receptors is dissected. Clearly, the next years will contribute to recognize the purinergic system as one of the key mediators/modulators of the inflammatory response in periphery and in the central nervous system.

Agasse, Bernardino, and Malva (Chap. 4) discuss the potential of subventricular zone cells as a resource for brain repair. Detailed information about subventricular zone niche of stem/progenitor cells, factors contributing to migration, differentiation, and survival of new neurons is provided. A special attention was given on the impact of brain injury and inflammatory mediators in the migration, differentiation, and survival of subventricular zone cells as endogenous/grafted resources for brain repair. The potential use (at the long-term) of adult brain stem/progenitor cells in the repair of injured central nervous system tissue is envisioned and discussed. Clearly, the stem/progenitor cells research is endowed with enormous potential for the future therapy of the major diseases afflicting the central nervous system. The future years will assist to the enthusiastic expansion in stem/progenitor cell research and hopefully to the outcome of new strategies for brain repair.

In Sect. 2, "Signaling and Inflammation in Aging," and Sect. 3, "Neurodegeneration and Inflammation in Age-Related Diseases," the concepts introduced in Sect. 1 will be used in the context of inflammatory reactions and signaling transduction in aging and disease.

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