The blood-brain barrier, which is formed by the endothelial cells that line cerebral microvessels, has an important role in maintaining a precisely regulated microenvironment for reliable neuronal signalling. At present, there is great interest in the association of brain microvessels, astrocytes and neurons to form functional 'neurovascular units', and recent studies have highlighted the importance of brain endothelial cells in this modular organization. Here, we explore specific interactions between the brain endothelium, astrocytes and neurons that may regulate blood-brain barrier function. An understanding of how these interactions are disturbed in pathological conditions could lead to the development of new protective and restorative therapies.
Glial cells are known to interact extensively with neuronal elements in the brain, influencing their activity. Astrocytes associated with synapses integrate neuronal inputs and release transmitters that modulate synaptic sensitivity. Glial cells participate in formation and rebuilding of synapses and play a prominent role in protection and repair of nervous tissue after damage. For glial cells to take an active part in plastic alterations under physiological conditions and pathological disturbances, extensive specific signaling, both within single cells and between cells, is required. In recent years, intensive research has led to our first insight into this signaling. We know there are active connections between astrocytes in the form of networks promoting Ca2+ and ATP signaling; we also know there is intense signaling between astrocytes, microglia, oligodendrocytes, and neurons, with an array of molecules acting as signaling substances. The cells must be functionally integrated to facilitate the enormous dynamics of and capacity for reconstruction within the nervous system. In this paper, we summarize some basic data on glial neuronal signaling to provide insight into synaptic modulation and reconstruction in physiology and protection and repair after damage.
This study investigates the effect of microglial activation on microglial glutamate transporters in vitro. Stimuli known to activate microglia and/or to be associated with pathological conditions with an impaired astroglial glutamate uptake were compared. Morphological changes and marked increases in ED1 antigen expression were found after 8-h incubation of rat microglia in 56 mM KCl, 1 ng/ml lipopolysaccharide (LPS), and 100 microM glutamate, as well as in acidic and basic conditions, showing that the cells were activated. Of the stimuli used, only LPS induced a significant release of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and was the only stimulus that increased microglial GLT-1 expression and glutamate uptake capacity after 12-h incubation. This effect was probably mediated by TNF-alpha, since this cytokine mimicked the effect of LPS. Furthermore, the effect of LPS was blocked by thalidomide, an inhibitor of TNF-alpha synthesis. Additionally, neutralizing antibodies against TNF-alpha also blocked the increase, indicating TNF-alpha as an inducer of GLT-1 expression in microglia. It was also found that preincubation with glutamate dose-dependently inhibited the microglial glutamate uptake. This could suggest different physiological functions for microglial and astroglial glutamate uptake and might indicate a reciprocal control of GLT-1 expression between microglia and astrocytes.
The recovery trajectory for hip fracture surgery may be shortened if nurses pay more attention to the individual patient's resources and motivation for rehabilitation. The application of an integrated care pathway with individualized care appears to enhance both rehabilitation outcomes and cost-effectiveness.
Almost none of the commonly occurring and frequently practiced medical interventions for patients who are sick-listed because of low back pain had any positive effects on either the recorded health measures or work resumption.
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