The Journal of physiology
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The Journal of physiology · Sep 2013
ReviewDoes epithelial sodium channel hyperactivity contribute to cystic fibrosis lung disease?
Airway epithelia absorb Na+ through the epithelial Na+ channel (ENaC) and secrete Cl- through the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. This balance maintains sufficient airway surface liquid hydration to permit efficient mucus clearance, which is needed to maintain sterility of the lung. Cystic fibrosis (CF) is a common autosomal recessive inherited disease caused by mutations in the CFTR gene that lead to the reduction or elimination of the CFTR protein. ⋯ Rehydrating CF mucus has become a recent clinical focus and yields important end-points for clinical trials. However, while ENaC hyperactivity in CF airways has been detected in vivo and in vitro, recent data have brought the role of ENaC in CF lung disease pathogenesis into question. This review will focus on our current understanding of the contribution of ENaC to CF pathogenesis.
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The Journal of physiology · Mar 2013
ReviewRole of nocturnal rostral fluid shift in the pathogenesis of obstructive and central sleep apnoea.
Obstructive sleep apnoea (OSA) is common in the general population and increases the risk of motor vehicle accidents due to hypersomnolence from sleep disruption, and risk of cardiovascular diseases owing to repetitive hypoxia, sympathetic nervous system activation, and systemic inflammation. In contrast, central sleep apnoea (CSA) is rare in the general population. Although their pathogenesis is multifactorial, the prevalence of both OSA and CSA is increased in patients with fluid retaining states, especially heart failure, where they are associated with increased mortality risk. ⋯ Some of this fluid may accumulate in the neck, increasing tissue pressure and causing the upper airway to narrow, thereby increasing its collapsibility and predisposing to OSA. In heart failure patients, with increased rostral fluid shift, fluid may additionally accumulate in the lungs, provoking hyperventilation and hypocapnia, driving below the apnoea threshold, leading to CSA. This review article will explore mechanisms by which overnight rostral fluid shift, and its prevention, can contribute to the pathogenesis and therapy of sleep apnoea.
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The Journal of physiology · Jan 2013
ReviewCerebral network disorders after stroke: evidence from imaging-based connectivity analyses of active and resting brain states in humans.
Stroke causes a sudden disruption of physiological brain function which leads to impairments of functional brain networks involved in voluntary movements. In some cases, the brain has the intrinsic capacity to reorganize itself, thereby compensating for the disruption of motor networks. In humans, such reorganization can be investigated in vivo using neuroimaging. ⋯ In addition, there is evidence that motor recovery is accompanied by a more random network topology with reduced local information processing. In conclusion, Stroke induces changes in functional and effective connectivity within and across hemispheres which relate to motor impairments and recovery thereof. Connectivity analyses may hence provide new insights into the pathophysiology underlying neurological deficits and may be further used to develop novel, neurobiologically informed treatment strategies.
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TRP channels were first identified as membrane proteins mediating phototransduction in fruit flies. Astrocytes were initially referred to as the silent elements of the nervous system. ⋯ Recent findings, however, put TRP channels and astrocytes in the spotlight, describe their ability to modulate the activity of specific sets of synapses, and raise some interesting questions. What makes astrocytes capable of exerting cell-specific effects on interneuronal signals? How do different synapses respond to changes in astrocytic function and in the local micro-structure of the neuropil? Can astrocytes be considered good candidate targets for therapeutic intervention to treat neurological diseases? Here I discuss the recent developments on TRP channels and astrocytes that have made us aware of the many structural and functional features of synapses that still need to be discovered and that could lead a new avant-garde in decoding the cellular and molecular basis of brain (dys)function.
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The Journal of physiology · Oct 2012
ReviewThe pharmacology of neuroplasticity induced by non-invasive brain stimulation: building models for the clinical use of CNS active drugs.
The term neuroplasticity encompasses structural and functional modifications of neuronal connectivity. Abnormal neuroplasticity is involved in various neuropsychiatric diseases, such as dystonia, epilepsy, migraine, Alzheimer's disease, fronto-temporal degeneration, schizophrenia, and post cerebral stroke. Drugs affecting neuroplasticity are increasingly used as therapeutics in these conditions. ⋯ We will (a) review the basics of neuroplasticity, as explored in animal experimentation, and relate these to our knowledge about neuroplasticity induced in humans by NIBS techniques. We will then (b) discuss pharmacological modulation of plasticity in animals and humans. Finally, we will (c) review abnormalities of plasticity in neuropsychiatric diseases, and discuss how the combination of NIBS with pharmacological intervention may improve our understanding of the pathophysiology of abnormal plasticity in these diseases and their purposeful pharmacological treatment.