Mechanisms by which signals from outside the CNS can alter microglial activation are also discussed. The authors describe animal studies indicating Stem Cell Compound Library that age-related changes in microglia cause impairment of neurogenesis and neuronal plasticity together with associated

cognitive deficits. Importantly, when considering extrapolation towards therapy in humans, reversing the neuroinflammation has functional benefits. The information in this review provides an important basis with which to understand how the ageing brain reacts to superimposed neurodegenerative pathology, the effects of systemic inflammation and reactions to brain injury. Since the observations of Corsellis and Bruton in the 1970s documenting neurodegenerative pathology in the brains of boxers suffering from dementia pugilistica, there have been intriguing hints linking traumatic brain

injury and subsequent long-term progressive neurodegeneration. There has recently been a resurgence of interest in this field, which has come in particular from North America, concerning repeated head injuries sustained as a result of sporting activities such as ice hockey and football and their associated long-term effects (chronic traumatic encephalopathy). The review by PLX4032 Colin Smith of the effects of traumatic brain injury, both single and repetitive, on microglial activation and neurodegeneration, is therefore particularly timely. He develops the argument that microglial activation as a response to

injury in the short tem is beneficial, removing cell debris and promoting tissue repair. However, if the activated state of microglia is not subsequently down-regulated, it may become self-perpetuating and lead to chronic neurodegeneration associated with accumulation of neurodegeneration-related proteins such as tau, amyloid-β and TDP-43. Stephen Gentleman considers in detail the relationship between accumulation of different neurodegeneration-associated proteins in the CNS and microglial activation: are they simply reacting to the pathology, Baf-A1 purchase are they instrumental in the pathogenesis of neurodegenerative disease, or both? He compares and contrasts our current knowledge of the contribution of microglia in a disorder with extracellular aggregation of protein (AD) and those with intracellular protein aggregations (amyotrophic lateral sclerosis and Parkinson’s disease). Clive Holmes considers the evidence that inflammation in the CNS cannot be considered in isolation from inflammation occurring elsewhere in the body (that is, systemic or peripheral inflammation). Information from clinical and preclinical studies shows that peripheral inflammation due to infection or other causes including rheumatoid arthritis, diabetes and atherosclerosis, has an effect on cognitive function both acutely and in the long term.