Philosophical transactions of the Royal Society of London. Series B, Biological sciences
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Philos. Trans. R. Soc. Lond., B, Biol. Sci. · Oct 2016
ReviewFunctional magnetic resonance imaging in chronic ischaemic stroke.
Ischaemic stroke is the leading cause of adult disability worldwide. Effective rehabilitation is hindered by uncertainty surrounding the underlying mechanisms that govern long-term ischaemic injury progression. Despite its potential as a sensitive non-invasive in vivo marker of brain function that may aid in the development of new treatments, blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has found limited application in the clinical research on chronic stage stroke progression. ⋯ Concomitant measurements of vascular reactivity, neuronal activity and metabolism in preclinical models of stroke are reviewed along with illustrative examples of post-ischaemic evolution in neuronal, glial and vascular function. The realization of the BOLD fMRI potential to propel stroke research is predicated on the carefully designed preclinical research establishing an ischaemia-specific quantitative model of BOLD signal contrast to provide the framework for interpretation of fMRI findings in clinical populations. This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'.
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Philos. Trans. R. Soc. Lond., B, Biol. Sci. · Aug 2016
ReviewThe homeostatic astroglia emerges from evolutionary specialization of neural cells.
Evolution of the nervous system progressed through cellular diversification and specialization of functions. Conceptually, the nervous system is composed from electrically excitable neuronal networks connected with chemical synapses and non-excitable glial cells that provide for homeostasis and defence. ⋯ In neuropathology, astrocytes may undergo reactive remodelling or degeneration; to a large extent, astroglial reactions define progression of the pathology and neurological outcome. This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'.
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Philos. Trans. R. Soc. Lond., B, Biol. Sci. · Sep 2015
ReviewContemporary approaches to neural circuit manipulation and mapping: focus on reward and addiction.
Tying complex psychological processes to precisely defined neural circuits is a major goal of systems and behavioural neuroscience. This is critical for understanding adaptive behaviour, and also how neural systems are altered in states of psychopathology, such as addiction. ⋯ Recent advances in technology allow for manipulation and mapping of genetically and anatomically defined neurons, which when used in concert with sophisticated behavioural models, have the potential to provide great insight into neural circuit bases of behaviour. Here we discuss contemporary approaches for understanding reward and addiction, with a focus on midbrain dopamine and cortico-striato-pallidal circuits.
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Peto's paradox is the lack of the expected trend in cancer incidence as a function of body size and lifespan across species. The leading hypothesis to explain this pattern is natural selection for differential cancer prevention in larger, longer lived species. We evaluate whether a similar effect exists within species, specifically humans. ⋯ We further demonstrate that grouping by anatomical site explains most of the remaining variation. Our results indicate that cancer risk depends not only on the number of stem cell divisions but varies enormously (approx. 10 000 times) depending on anatomical site. We conclude that variation in risk of human cancer types is analogous to the paradoxical lack of variation in cancer incidence among animal species and may likewise be understood as a result of evolution by natural selection.
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Studies of body size evolution, and life-history theory in general, are conducted without taking into account cancer as a factor that can end an organism's reproductive lifespan. This reflects a tacit assumption that predation, parasitism and starvation are of overriding importance in the wild. We argue here that even if deaths directly attributable to cancer are a rarity in studies of natural populations, it remains incorrect to infer that cancer has not been of importance in shaping observed life histories. ⋯ We also discuss reasons why patterns across species can differ from within-species predictions. Even if natural selection diminishes cancer susceptibility differences between species, within-species differences can remain. In many sexually dimorphic cases, we predict males to be more cancer-prone than females, forming an understudied component of sexual conflict.