Microglia are unique among the major cell types of the central nervous system (CNS) in being not derived from the neuroectoderm. Ultimately derived from myeloid precursors, they are representatives of the monocyte/macrophage series of cells, and can be regarded as the resident cells of the innate immune system in the CNS. ‘Neuroinflammation’, in the form of activation BMS 354825 of microglia, is an almost ubiquitous feature of diseases of the CNS. Is neuroinflammation simply a reaction to tissue damage and disease or, alternatively, is it an integral component of CNS disease,

promoting neuronal and synaptic damage and important in pathogenesis? Consideration of organs other than the brain certainly tells us that chronic inflammation is harmful, causing tissue damage and fibrosis. Examples include inflammation of synovial joints resulting in arthropathy and damaging chronic inflammation of the liver, pancreas, gastrointestinal tract and lungs. Early proponents of the concept that neuroinflammation

is important in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD) include Griffin and McGeer in the 1980s. Initially, such views were controversial and met with considerable scepticism but in subsequent years, as new evidence emerged, the role www.selleckchem.com/products/DAPT-GSI-IX.html of neuroinflammation in AD has been given serious consideration by many others. An important stage was in the 1990s when epidemiological studies of use of non-steroidal anti-inflammatory drugs began to provide evidence of a role for neuroinflammation in the pathogenesis of AD. More recently, this concept has been given

further support by genome-wide association studies of AD demonstrating that variation in genes encoding several inflammation-related proteins influences risk of AD development. In this special issue of Neuropathology and Applied Neurobiology, we are privileged to have reviews written by international leaders in the field of neuroinflammation to provide an update and new insights into the role of microglial activation in ageing and in neurodegenerative disease. In the first review, we set the scene in describing how in the normal Dapagliflozin CNS microglia appear quiescent and downregulated, and how they become activated in disease states. Evidence mainly from in vitro and rodent studies indicates that microglia can exist in different activation states, prompted by different stimuli and with different functional consequences. We discuss to what extent these different activation states can be identified in the human brain, and raise the question as to whether manipulation of the microglial state of activation may in future be of therapeutic use. In the second review, Diana Norden and Jonathan Godbout discuss evidence of alterations of microglia in the ageing process, rendering them primed or sensitized to react to stimuli and with the balance of cytokine expression biased towards a pro-inflammatory state.