486 research outputs found
Functions and mechanisms of interleukin 1 in the brain
No full textInterleukin 1 (IL-1), a cytokine with diverse actions, has been proposed as a mediator of both beneficial and detrimental responses to inflammation and injury. Many of the actions of IL-1, such as those on behaviour, neuroendocrine function, sleep, fever and metabolism, are mediated by the CNS, as described here by Nancy Rothwell. IL-1 can be synthesized and act locally within the brain to influence neuronal and glial function, and has been strongly implicated in normal brain development and responses to brain injury. A number of distinct sites and mechanisms of action have been proposed to explain these diverse effects of IL-1 in the brain, probably involving multiple receptor subtypes and complex interactions with neurotransmitters and neuropeptides. © 1991
Functions and mechanisms of interleukin 1 in the brain
No full textInterleukin 1 (IL-1), a cytokine with diverse actions, has been proposed as a mediator of both beneficial and detrimental responses to inflammation and injury. Many of the actions of IL-1, such as those on behaviour, neuroendocrine function, sleep, fever and metabolism, are mediated by the CNS, as described here by Nancy Rothwell. IL-1 can be synthesized and act locally within the brain to influence neuronal and glial function, and has been strongly implicated in normal brain development and responses to brain injury. A number of distinct sites and mechanisms of action have been proposed to explain these diverse effects of IL-1 in the brain, probably involving multiple receptor subtypes and complex interactions with neurotransmitters and neuropeptides. © 1991
Lipocortin-1: Cellular mechanisms and clinical relevance
No full textLipocortin-1, a 37 kDa member of the annexin superfamily of proteins, originally evoked interest as one of the 'second messengers' of the antiinflammatory actions of the glucocorticoids. Subsequent research has shown that the protein plays a major regulatory role in systems as diverse as cell-growth regulation and differentiation, neutrophil migration, CNS responses to cytokines, neuroendocrine secretion and neurodegeneration. The role of lipocortin-1 in mediating glucocorticoid-induced effects in these systems has been demonstrated using immunoneutralization strategies and by mimicking steroid actions with highly purified or recombinant lipocortin-1 or its biologically active peptide fragments. Originally the mode of action of lipocortin-1 seemed to be largely through inhibition of prostaglandin formation, but it is now clear that it can modify other aspects of cell function, perhaps pointing to a more fundamental mechanism than was originally envisaged. In this article Rod Flower and Nancy Rothwell review the nature, possible mechanisms and clinical relevance of these diverse actions of lipocortin-1
Cerebellar Theta-Burst Stimulation Impairs Memory Consolidation in Eyeblink Classical Conditioning
No full textAssociative learning of sensorimotor contingences, as it occurs in eyeblink classical conditioning (EBCC), is known to involve the cerebellum, but its mechanism remains controversial. EBCC involves a sequence of learning processes which are thought to occur in the cerebellar cortex and deep cerebellar nuclei. Recently, the extinction phase of EBCC has been shown to be modulated after one week by cerebellar continuous theta-burst stimulation (cTBS). Here, we asked whether cerebellar cTBS could affect retention and reacquisition of conditioned responses (CRs) tested immediately after conditioning. We also investigated a possible lateralized cerebellar control of EBCC by applying cTBS on both the right and left cerebellar hemispheres. Both right and left cerebellar cTBSs induced a statistically significant impairment in retention and new acquisition of conditioned responses (CRs), the disruption effect being marginally more effective when the left cerebellar hemisphere was stimulated. These data support a model in which cTBS impairs retention and reacquisition of CR in the cerebellum, possibly by interfering with the transfer of memory to the deep cerebellar nuclei
Lipocortin-1 is an endogenous inhibitor of ischemic damage in the rat brain
No full textLipocortin-1 (annexin-1) is an endogenous peptide with antiinflammatory properties. We have previously demonstrated lipocortin immunoreactivity in certain glial cells and neurons in the rat brain (Strijbos, P. J. L. M., F. J. H. Tilders, F. Carey, R. Forder, and N. J. Rothwell. 1990. Brain Res. In press.), and have shown that an NH2-terminal fragment (1-188) of lipocortin-1 inhibits the central and peripheral actions of cytokines on fever and thermogenesis in the rat in vivo (Carey, F., R. Forder, M. D. Edge, A. R. Greene, M. A. Horan, P. J. L. M. Strijbos, and N. J. Rothwell. 1990. Am. J. Physiol. 259:R266; and Strijbos, P. J. L. M., J. L. Browning, M. Ward, R. Forder, F. Carey, M. A. Horan, and N. J. Rothwell. 1991. Br. J. Pharmacol. In press.). We now report that intracerebroventricular administration of lipocortin-1 fragment causes marked inhibition of infarct size (60%) and cerebral edema (46%) measured 2 h after cerebral ischemia (middle cerebral artery occlusion) in the rat in vivo. The lipocortin-1 fragment was effective when administered 10 min after induction of ischemia. Ischemia caused increased expression of lipocortin-1 around the area of infarction as demonstrated by immunocytochemistry. Intra-cerebroventricular injection of neutralizing antilipocortin-1 fragment antiserum increased the size of infarct (53%) and the development of edema (29%). These findings indicate that lipocortin-1 is an endogenous inhibitor of cerebral ischemia with considerable therapeutic potential
Lipocortin-1 is an endogenous inhibitor of ischemic damage in the rat brain
No full textLipocortin-1 (annexin-1) is an endogenous peptide with antiinflammatory properties. We have previously demonstrated lipocortin immunoreactivity in certain glial cells and neurons in the rat brain (Strijbos, P. J. L. M., F. J. H. Tilders, F. Carey, R. Forder, and N. J. Rothwell. 1990. Brain Res. In press.), and have shown that an NH2-terminal fragment (1-188) of lipocortin-1 inhibits the central and peripheral actions of cytokines on fever and thermogenesis in the rat in vivo (Carey, F., R. Forder, M. D. Edge, A. R. Greene, M. A. Horan, P. J. L. M. Strijbos, and N. J. Rothwell. 1990. Am. J. Physiol. 259:R266; and Strijbos, P. J. L. M., J. L. Browning, M. Ward, R. Forder, F. Carey, M. A. Horan, and N. J. Rothwell. 1991. Br. J. Pharmacol. In press.). We now report that intracerebroventricular administration of lipocortin-1 fragment causes marked inhibition of infarct size (60%) and cerebral edema (46%) measured 2 h after cerebral ischemia (middle cerebral artery occlusion) in the rat in vivo. The lipocortin-1 fragment was effective when administered 10 min after induction of ischemia. Ischemia caused increased expression of lipocortin-1 around the area of infarction as demonstrated by immunocytochemistry. Intra-cerebroventricular injection of neutralizing antilipocortin-1 fragment antiserum increased the size of infarct (53%) and the development of edema (29%). These findings indicate that lipocortin-1 is an endogenous inhibitor of cerebral ischemia with considerable therapeutic potential
Regaining Motor Control in Musician's Dystonia by Restoring Sensorimotor Organization
No full textProfessional musicians are an excellent human model of long term effects of skilled motor training on the structure and function of the motor system. However, such effects are accompanied by an increased risk of developing motor abnormalities, in particular musician's dystonia. Previously we found that there was an expanded spatial integration of proprioceptive input into the hand area of motor cortex (sensorimotor organisation, SMO) in healthy musicians as tested with a transcranial magnetic stimulation (TMS) paradigm. In musician's dystonia, this expansion was even larger, resulting in a complete lack of somatotopic organisation. We hypothesised that the disordered motor control in musician's dystonia is a consequence of the disordered SMO.
In the present paper we test this idea by giving pianists with musician's dystonia 15 min experience of a modified proprioceptive training task. This restored SMO towards that seen in healthy pianists. Crucially, motor control of the affected task improved significantly and objectively as measured with a MIDI piano, and the amount of behavioural improvement was significantly correlated to the degree of sensorimotor re-organisation. In healthy pianists and non-musicians, the SMO and motor performance remained essentially unchanged. These findings suggest a link between the differentiation of SMO in the hand motor cortex and the degree of motor control of intensively practiced tasks in highly skilled individuals
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