Brain research
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Comparative Study
Chronic intermittent ethanol exposure enhances NMDA-receptor-mediated synaptic responses and NMDA receptor expression in hippocampal CA1 region.
In previous studies, we found that chronic intermittent ethanol (CIE) treatment-a model of ethanol consumption in which animals are exposed to and withdrawn from intoxicating levels of ethanol on a daily basis-produces neuroadaptive changes in hippocampal area CA1 excitatory synaptic transmission and plasticity. Synaptic responses mediated by N-methyl-D-aspartate (NMDA) receptors are known to be sensitive to ethanol and could play an important role in the neuroadaptive changes induced by CIE treatment. To address this issue, we compared electrophysiological recordings of pharmacologically isolated NMDA-receptor-mediated field excitatory postsynaptic potentials (fEPSPs) in the CA1 region of hippocampal slices prepared from control rats and rats exposed to 2 weeks of CIE treatment administered by vapor inhalation. ⋯ However, following 7 days of withdrawal from CIE treatment, NMDA-receptor-mediated fEPSPs were augmented relative to age-matched controls. Western blot analysis of NMDA receptor subunit expression showed that, at 7 days of withdrawal, the level of protein for NR2A and NR2B subunits was elevated in the CA1 region of hippocampal slices from CIE-treated animals compared with slices from age-matched controls. These results are consistent with an involvement of NMDA-receptor-mediated synaptic responses in the neuroadaptive effects of CIE on hippocampal physiology and suggest that such changes may contribute to ethanol-induced changes in processes dependent on NMDA-receptor-mediated synaptic responses such as learning and memory, neural development, hyperexcitability and seizures, and neurotoxicity.
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Comparative Study
Antiallodynic effects of NMDA glycine(B) antagonists in neuropathic pain: possible peripheral mechanisms.
NMDA receptors are implicated in central sensitisation underlying chronic pain, and NMDA antagonists have a potential for the treatment of neuropathic pain. Functional NMDA receptors are also present on primary afferents, where they may play a role in pro-nociceptive plasticity. The importance of this mechanism in neuropathic pain remains unclear. ⋯ However, only L-701,324 was able to inhibit neuronal responses to NMDA in the antihyperalgesic dose range; 5,7-DCK was inactive on NMDA responses up to 46.4 mg/kg i.v. or 68.1 mg/kg i.p. Consistent with the lack of inhibition of central NMDA-evoked activity, 5,7-DCK did not alter spontaneous behaviour in the open field test, whereas it was significantly inhibited by L-701,324. Thus, peripheral NMDA receptors may substantially contribute to the efficacy of NMDA antagonists in neuropathic pain.
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Intracranial pressure (ICP) was monitored to evaluate the therapeutic effect of hyperbaric oxygen (HBO(2)) treatment following traumatic brain injury (TBI). This subject is controversial. The aim of our study was to determine whether HBO(2) treatment has a therapeutic effect on ICP dynamics and survival following severe fluid percussion brain injury (FPBI) in rats. ⋯ Covariance analysis confirmed significant differences between slopes for groups A and B (F = 148.04, P < 0.001; df = 2,177), i.e., a significant difference in mean rate of ICP elevation. By the end of the experiment, 3 out of 7 rats from group A had died, but none from group B. We conclude that the application of HBO(2) during the early phase of severe FPBI significantly diminished ICP elevation rate and decreased mortality level.
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This study investigated whether the opportunity to avoid or escape the open arms of an elevated plus-maze (EPM) affects the antinociceptive response observed when mice are subjected to open arm confinement. Furthermore, in order to better characterize the relationship between emotion and antinociception in the EPM, we examined the behavioral effects of midazolam injection into the midbrain periaqueductal gray matter (PAG). As our main aim was to evaluate the relevance of different levels of approach-avoid conflict (i.e. the presence of open and closed arms) to maze-induced antinociception, mice were exposed to one of three types of EPM-a standard EPM (sEPM), an open EPM (oEPM: four open arms) or, as a control condition, an enclosed EPM (eEPM: four enclosed arms). ⋯ Intra-PAG infusions of midazolam failed to block oEPM-induced antinociception or to alter sEPM-induced anxiety in mice that had received formalin injection. However, under normal test conditions (i.e. in the absence of formalin-induced nociceptive stimulation), intra-PAG midazolam produced clear anti-anxiety effects in mice exposed to the sEPM. Findings are discussed in terms of different emotional states induced by the oEPM and sEPM and the influence of concurrent nociceptive stimulation on the anti-anxiety effect of intra-PAG midazolam.
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Comparative Study
The NMDA receptor NR2B subunit contributes to epileptogenesis in human cortical dysplasia.
Cortical dysplasia (CD) is often associated with pharmacoresistant epilepsy. Previous studies showed increased expression of the NMDA receptor subunit NR2B in dysplastic and epileptic human neocortex. We tested the hypothesis that differential increase of NR2B constitutes an epileptogenic mechanism in humans. ⋯ In both dysplastic and non-dysplastic slices, EFP were suppressed by a non-specific NMDAR antagonist (APV) or AMPA receptor antagonist (CNQX). These results provide additional evidence that the differential expression of NR2B in dysplastic human neocortex may play a role in the expression of in-situ epileptogenesis in human CD. NR2B may constitute a target for new diagnostic and pharmacotherapeutic approaches.