Development and regeneration of the vertebrate brain

The vertebrate brain is hierarchically assembled about orthogonal axes using organizing centers that control cascades of signaling events. The reiterative generation of these centers at defined times, and in precise spatial locations, leads to the conversion of a contiguous and homogenous epithelial sheet into the most complex biological tissue in the animal kingdom. The critical events orchestrating the construction of a "typical" vertebrate brain are described. Attention is focused on specification of major brain regions common across the vertebrate phylogeny, rather than on the differentiation of constituent cell types and specific cytoarchitectures. By uncloaking the complex spatial interactions that unfold temporally during the build of the vertebrate brain, it becomes clear why regeneration of this tissue following injury is such a challenging task. And yet, while mammalian brains fail to regenerate, the brains of non-mammalian vertebrates, such as teleosts, reptiles and amphibians, can successfully reconstitute brain tissue following traumatic injury. Understanding the molecular and cellular bases of this remarkable regenerative capacity is revealing the importance of developmental programs, as well as exposing unexpected roles for extraneous processes such as inflammation. Recent discoveries are now fuelling hope for future therapeutic approaches that will ameliorate the debilitating consequences of brain injury in humans

Giant cell arteritis and polymyalgia rheumatica: current challenges and opportunities

The fields of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) have advanced rapidly, resulting in a new understanding of these diseases. Fast-track strategies and improved awareness programmes that prevent irreversible sight loss through early diagnosis and treatment are a notable advance. Ultrasonography and other imaging techniques have been introduced into routine clinical practice and there have been promising reports on the efficacy of biologic agents, particularly IL-6 antagonists such as tocilizumab, in treating these conditions. Along with these developments, which should improve outcomes in patients with GCA and PMR, new questions and unmet needs have emerged; future research should address which pathogenetic mechanisms contribute to the different phases and clinical phenotypes of GCA, what role imaging has in the early diagnosis and monitoring of GCA and PMR, and in which patients and phases of these diseases novel biologic drugs should be used. This article discusses the implications of recent developments in our understanding of GCA and PMR, as well as the unmet needs concerning epidemiology, pathogenesis, imaging and treatment of these diseases