Brain research
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Inflammation induces an upregulation of sodium channels in sensory neurons. This most likely occurs as a result of the retrograde transport of cytochemical mediators released during the inflammatory response. The purpose of this study was to determine the effect of the subcutaneous administration of one such mediator, nerve growth factor (NGF), on the production of sodium channels in neurons of the rat dorsal root ganglion. ⋯ Sodium channel labeling was found to increase dramatically in the small neurons of the associated dorsal root ganglia beginning at 23 h, reached maximum intensity by 1 week, and persisted for up to 3 months post-injection. Pre-blocking NGF with anti-NGF prevented the NGF-induced decrease in paw withdrawal latencies and significantly reduced the intensity of sodium channel labeling. The results indicate that NGF is an important mediator both in the development of acute hyperalgesia and in the stimulation of sodium channel production in dorsal root ganglia during inflammation.
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Clinical Trial
Duration and distribution of experimental muscle hyperalgesia in humans following combined infusions of serotonin and bradykinin.
The present study examined distribution and duration of muscle hyperalgesia to pressure stimuli after intramuscular bolus-infusions of serotonin (5-HT, 20 nmol) and bradykinin (BKN, 10 nmol) in 10 volunteers. Infusions were given into the tibialis anterior (TA) muscle over 20 s with an inter-infusions interval of 3 min. Infusions of isotonic saline (NaCl, 0.9%) were given as control. ⋯ Serotonin may enhance the effect of bradykinin in producing experimental muscle pain and muscle hyperalgesia to mechanical stimuli. The combination of serotonin and bradykinin can produce muscle hyperalgesia, lasted for up to 40 min and located within the muscle. No widespread hyperalgesia to the ankle and other leg (tested at 10 cm below the patella and ankle) was observed suggesting a predominant peripheral origin of the experimentally induced hyperalgesic stage.
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Clinical Trial Controlled Clinical Trial
Deficits in the coordination of agonist and antagonist muscles in stroke patients: implications for normal motor control.
Movement impairments about a single joint in stroke patients may be related to deficits in the central regulation of stretch reflex (SR) thresholds of agonist and antagonist muscles. One boundary of the SR threshold range for elbow flexor and extensor muscles was measured in hemiparetic subjects by analysing electromyographic activity during stretching of relaxed muscles at seven different velocities. For each velocity, dynamic SR thresholds were measured as angles at which electromyographic activity appeared. ⋯ The range in which reciprocally organized agonist and antagonist muscle activity could be generated was limited in all but one subject. When attempting to produce torque from positions outside their measured range of movement, excessive muscle coactivation occurred, typically producing no or paradoxical motion in the opposite direction. Results suggest a relationship between spasticity measured at rest and the movement deficit in stroke by demonstrating a link between motor deficits and control deficits in the central regulation of individual SR thresholds.
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The function of the neuronal high molecular weight microtubule-associated proteins (MAPs) MAP1b and MAP2 is regulated by the degree of their phosphorylation, which in turn is controlled by the activities of protein kinases and protein phosphatases (PP). To investigate the role of PP in the regulation of the phosphorylation of MAP1b and MAP2, we used okadaic acid and cyclosporin A to selectively inhibit PP2A and PP2B activities, respectively, in metabolically competent rat brain slices. The alteration of the phosphorylation levels of MAP1b and MAP2 was examined by Western blots using several phosphorylation-dependent antibodies to these proteins. ⋯ Immunocytochemically, a marked increase in neuronal staining in inhibitor-treated tissue was observed with antibodies to the phosphorylated MAP1b. The inhibition of PP2A but not of PP2B also induced phosphorylation of MAP2 at multiple sites and impaired its microtubule binding activity. These results suggest that PP2A might be the major PP that participates in regulation of the phosphorylation of MAP1b and MAP2 and their biological activities.
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Accumulating evidence suggests that the neurotrophin receptors, Trks and p75, play distinct roles in regulating cells survival and death, with Trks important for cell survival, and p75 acting to induce cell death. Here, we provide evidence that, in neuronal cultures from rat cerebral cortex, nerve growth factor (NGF) exerts neuroprotective actions via p75. Incubating cultures with NGF for 1-24 h protected cortical neurons from delayed cytotoxicity induced by brief exposure to glutamate. ⋯ Distinct signaling pathways mobilized by NGF and BDNF were also revealed in that NGF but not BDNF stimulated significant production of ceramides, whereas BDNF but not NGF caused persistent activation of mitogen-activated protein kinases. These results indicate that, although NGF and BDNF both protect cortical neurons from excitotoxicity, the mechanisms involved in their effects are totally different. The present results are, to our knowledge, the first to demonstrate the principal involvement of p75 in cytoprotective actions of neurotrophins.