Neuroscience
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In order to elucidate the mechanism(s) of neuronal protection by hypothermia against ischemic damage, we examined the effect of lowering temperature on the microglial activation that is thought to cause the development of ischemia-induced neuronal damages. Cultured microglia from neonatal rats were measured for microglial activation by the following indices: production of superoxide and nitric oxide by the methods of acetyl-cytochrome c reduction and nitrite accumulation in the culture medium, respectively, and cell proliferation evaluated by [3H]thymidine uptake. At 30 degrees C, superoxide production induced by phorbol ester was approximately as low as 30% of the control at 37 degrees C, and nitric oxide production after addition of lipopolysaccharide was decreased to approximately 25% of the control. ⋯ In addition, the proliferation of microglia was remarkably inhibited at 30 degrees C. The level of proliferation in the hypothermic condition is much lower in microglia (14% of the control) than those in astrocytes cultured from brain cortices (96%) and fibroblasts cultured from brain meninges (53%), suggesting that the microglial activation is highly susceptible to lowering temperature. The present study indicates that hypothermia potently inhibits proliferation, superoxide and nitric oxide production of cultured microglia and that the hypothermic protection against postischemic neuronal damage might be, at least in part, due to the suppression of microglial activation.
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The N-methyl-D-aspartate-evoked release of [3H]acetylcholine previously formed from [3H]choline was estimated in striosome- (identified by [3H]naloxone binding) or matrix-enriched areas of the rat striatum using an in vitro microsuperfusion procedure. Experiments were performed in either the absence or the presence of dopaminergic and/or GABAergic receptor antagonists. Although the cell bodies of the cholinergic interneurons were mainly found in the matrix, in the absence of magnesium, N-methyl-D-aspartate (50 microM) stimulated the release of [3H]acetylcholine in both striatal compartments. ⋯ Indicating that released GABA facilitates N-methyl-D-aspartate responses, the blockade of GABAA receptors with bicuculline (5 microM) reduced the 50 microM N-methyl-D-aspartate-evoked release of [3H]acetylcholine in both striatal compartments and the 1 mM N-methyl-D-aspartate+D-serine response in the matrix. These effects result from an inhibition by GABA of the evoked release of dopamine, since the reducing effects of bicuculline on N-methyl-D-aspartate responses were not observed under the complete blockade of dopaminergic transmission by the D1 and D2 receptor antagonists. Further demonstrating a facilitatory role of GABA in the control of N-methyl-D-aspartate-evoked release of [3H]acetylcholine, in the presence of bicuculline, (-)-sulpiride and SCH23390 alone or in combination enhanced, in both compartments, the responses induced not only by 1 mM N-methyl-D-aspartate+D-serine, but also by 50 microM N-methyl-D-aspartate.
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The protein Fos is a transcription factor which is quickly induced in response to a variety of extracellular signals. Since this protein is expressed in a variety of neuronal systems in response to activation of synaptic afferents, it has been suggested that it might contribute to activity-dependent plasticity in neural networks. The present study investigated the effect of cortical electrical stimulation on the expression of Fos in the basal ganglia in the rat, a group of structures that participate in sensorimotor learning. ⋯ In the subthalamic nucleus, Fos expression evoked by cortical stimulation is also confined to discrete regions of the nucleus, the localizations corresponding to the primary projection site of the stimulated cortical cells. These results indicate that in addition to its phasic synaptic influence on the basal ganglia, the cerebral cortex could exert a long-term effect on the functional state of this system via a genomic control. Since the basal ganglia are involved in sensorimotor learning and motor habit formation, it is tempting to speculate that the activity-dependent Fos induction at corticostriatal and subthalamic synapses may contribute to consolidate the functionality of the neuronal networks activated during the completion of given motor tasks.
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Nociceptin (a heptadecapeptide also known as orphanin FQ) is a potent endogenous agonist of the opioid receptor-like1 receptor and has a sequence similar to dynorphin A. It has been reported that intracerebroventricularly injected nociceptin produced hyperalgesia in mice and that intrathecal injection of nociceptin inhibits the spinal sensitization. In the present study, we investigated the effect of intrathecally administered nociceptin in the rat formalin test (a model of inflammatory pain) and the rat hot plate test. ⋯ These effects of nociceptin were not antagonized by the co-administration of naloxone. Intrathecal injection of nociceptin had no effect on the hot plate test. These data suggest that nociceptin plays an important role in spinal nociceptive transmission through the activation of a naloxone-insensitive receptor, and spinally administered nociceptin produces an analgesic effect during the rat formalin test, but not the hot plate test.
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Tight ligation of the fifth and sixth lumbar segmental nerves in the rat provides a model of neuropathic pain. We used this model to assess the changes in primary afferent input to the dorsal horn in neuropathic pain syndromes. Dorsal roots and ganglia were examined for up to 32 weeks following segmental nerve ligation. ⋯ These findings indicate that although there is a great loss of dorsal root ganglion cells, there is dramatic sprouting of myelinated fibres and possibly some sprouting of unmyelinated fibres in the dorsal roots. Additionally, a difference in the responses of unmyelinated and myelinated fibres to this peripheral nerve injury is revealed. These changes in dorsal root ganglion cells and their central axons may underlie certain aspects of abnormal pain syndromes because of changes in the types and quantity of input the dorsal horn receives.