Neuroscience
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Comparative Study
Chronic morphine administration results in tolerance to delta opioid receptor-mediated antinociception.
Delta opioid receptor agonists produce only a moderate degree of antinociception, possibly reflecting the predominantly intracellular location of delta opioid receptor. However, recent studies suggest that short term morphine pretreatment can increase delta opioid receptor-mediated antinociception by promoting the translocation of delta opioid receptor to the cell surface. Even more striking sensitization has been reported after long term morphine pretreatment and withdrawal in locomotor tests. ⋯ However, consistent with previous reports, short term (2 day) pretreatment with morphine did result in sensitization to [D-Ala2,Glu4]-deltorphin. Subsequent in vitro analysis, using [125I][D-Ala2,Glu4]-deltorphin or guanosine 5'(gamma-35S-thio) triphosphate autoradiography, did not reveal any changes in delta opioid receptor binding or function resulting from chronic morphine pretreatment. In conclusion, chronic morphine pretreatment caused tolerance to delta opioid receptor-mediated behavioral effects with no clear change at the receptor level.
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Comparative Study
Bone marrow stromal cells upregulate expression of bone morphogenetic proteins 2 and 4, gap junction protein connexin-43 and synaptophysin after stroke in rats.
Bone morphogenetic proteins play a key role in astrocytic differentiation. Astrocytes express the gap junctional protein connexin-43, which permits exchange of small molecules in brain and enhances synaptic efficacy. Bone marrow stromal cells produce soluble factors including bone morphogenetic protein 2 and bone morphogenetic protein 4 (bone morphogenetic protein 2/4) in ischemic brain. ⋯ Administration of bone marrow stromal cells significantly (P<0.05) promoted the proliferating cell astrocytic differentiation, and increased bone morphogenetic protein 2/4, connexin-43 and synaptophysin expression in the ischemic boundary zone compared with the controls, respectively. Bone morphogenetic protein 2/4 expression correlated with the expression of connexin-43 (r=0.84, P<0.05) and connexin-43 expression correlated with the expression of synaptophysin (r=0.73, P<0.05) in the ischemic boundary zone, respectively. Administration of bone marrow stromal cells via an intra-carotid route increases endogenous brain bone morphogenetic protein 2/4 and connexin-43 expression in astrocytes and promotes synaptophysin expression, which may benefit functional recovery after stroke in rats.
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Comparative Study
Role of interleukin-6 in lipopolysaccharide-induced brain injury and behavioral dysfunction in neonatal rats.
There are increasing data in support of the hypothesis that inflammatory cytokines are involved in neonatal white matter damage. Despite extensive study of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta, the role of interleukin-6 in the development of white matter damage is largely unknown. In the present study, the role(s) of interleukin-6 in mediating lipopolysaccharide-induced brain injury and behavioral changes was investigated by the intracerebral injection of lipopolysaccharide with interleukin-6 neutralizing antibody in the 5-day-old rat brain. ⋯ However, no changes of tumor necrosis factor-alpha and interleukin-1beta were detected. In contrast, no histopathological changes and glial activation were observed in rats injected with only interleukin-6. The present study indicates that the contribution to brain injury by interleukin-6 depends on its interaction with other lipopolysaccharide-induced agents and not on interleukin-6 alone.
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Comparative Study
Cytokine-induced activation of glial cells in the mouse brain is enhanced at an advanced age.
Numerous neurological diseases which include neuroinflammatory components exhibit an age-related prevalence. The aging process is characterized by an increase of inflammatory mediators both systemically and in the brain, which may prime glial cells. However, little information is available on age-related changes in the glial response of the healthy aging brain to an inflammatory challenge. ⋯ This indicated that glial cell changes were not secondary to neuronal death. Altogether, the findings demonstrate for the first time enhanced activation of glial cells in the old brain, compared with young and middle-aged subjects, in response to cytokine exposure. Interestingly, the results also suggest that such enhancement does not develop gradually since youth, but appears characterized by relatively late onset.
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Comparative Study
A role for glutamate and glia in the fast network oscillations preceding spreading depression.
The mechanism of the propagation of spreading depression is unclear. Classical theories proposed a self-maintained cycle fed by elevated potassium and/or glutamate in the extracellular space. Earlier we found in vivo a characteristic oscillatory field activity that is synchronous in a strip of tissue ahead of the oncoming wave of neuron depolarization and that occurs before the extracellular potassium level begins to rise [Herreras O, Largo C, Ibarz JM, Somjen GG, Marrín del Río R (1994) Role of neuronal synchronizing mechanisms in the propagation of spreading depression in the in vivo hippocampus. ⋯ Also, the amplitude of the population spikes within the burst diminished as individual cells fired fewer action potentials, although still phase-locked with population spikes. The effects of glial metabolic impairment were observed within the period when neuron electrical properties were still normal, and were blocked by glutamate receptor antagonists. These data suggest that glutamate released from glial cells and possibly also from neurons has a role in the generation of oscillations and neuron firing synchronization that precede the spreading depression-related depolarization, but additional mechanisms are required to fully explain the onset and propagation of spreading depression.