Brain research
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Comparative Study
Na+/Ca2+ exchanger 1 alters in pyramidal cells and expresses in astrocytes of the gerbil hippocampal CA1 region after ischemia.
Alterations of immunoreactivity and protein contents of Na(+)/Ca(2+) exchanger 1 (NCX1) were observed in the gerbil hippocampus proper after 5 min of transient forebrain ischemia. NCX1 immunoreactivity was significantly changed in the hippocampal CA1 region, but not in the CA2/3 region after ischemia/reperfusion. In the sham-operated group, NCX1 immunoreactivity was mainly detected in CA1 pyramidal cells. ⋯ From 3 days post-ischemia, NCX1 immunoreactivity was expressed in astrocytes in the strata oriens and radiatum. Ischemia-induced changes in NCX1 protein contents in the hippocampus proper concurred with immunohistochemical data post-ischemia. Our results suggest that changes in NCX1 in CA1 pyramidal cells and astrocytes after ischemia are associated with intracellular Na(+) concentrations and that NCX1 may induce an intracellular calcium overload, which may be related to neuronal death.
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Neuroglobin (NGB) is a recently characterized heme globin expressed primarily in retinal nerve cells and at very low levels in endocrine-active regions of vertebrate brains. When artificially over-expressed, NGB reduces the infarct size observed after transient Middle Cerebral Artery occlusion (tMCAo) in rats. This study addresses the post-ischemic NGB expression in vivo. ⋯ In the ischemic territory we did not observe selective sparing of NGB expressing neurons. No significant change in the NGB/NeuN ratio was observed. Our data indicate that endogenous expressed NGB does not provide protection against ischemic injury induced by tMCAo in SHRs.
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Immunohistochemical study was performed to examine if calcium-binding proteins are involved in the degeneration of motor neurons in the brain stems and the spinal cords of transgenic mice carrying a G93A mutant human SOD1 gene. Specimens from age-matched non-transgenic wild-type mice served as controls. In the spinal cord of the controls, the density of parvalbumin-immunoreactive neurons was highest in the large anterior horn neurons and lower in the posterior horn neurons in the spinal cord. ⋯ Immunoblotting analysis revealed a significant reduction of immunoreactivity to parvalbumin antibody in transgenic mice compared with the controls. In the brain stem, parvalbumin-positive oculomotor and abducens neurons and the calbindin D-28k-positive sixth nucleus were well-preserved in transgenic mice as well as in the controls. Thus, the diffuse and severe loss of parvalbumin immunoreactivity of large motor neurons even at early stages in SOD1-transgenic mice and the absence of calbindin D-28k immunoreactivity of normal large motor neurons suggest that these calcium-binding proteins may contribute to selective vulnerability and an early loss of function of large motor neurons in this SOD1-transgenic mouse model.
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Previous studies have demonstrated the virtual lack of analgesia in mu opioid receptor knockout mice after systemic administration of morphine. Thus, it has been suggested that analgesic actions of morphine are produced via the mu opioid receptor, despite its ability to bind to kappa and delta receptors in vitro. However, it is not clear whether the results of these studies reflect the effect of morphine in the spinal cord. ⋯ SNC80 (a selective delta-opioid receptor agonist) was not antinociceptive even in wild type mice. The present study demonstrated that morphine can produce thermal antinociception via the kappa opioid receptor in the spinal cord in the absence of the mu opioid receptor. Lower potency of U50,488H in mu opioid receptor knockout mice suggests interaction between kappa and mu opioid receptors at the spinal level.
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Comparative Study
Blocking mu opioid receptors in the spinal cord prevents the analgesic action by subsequent systemic opioids.
Systemically administered mu opioids may produce analgesia through inhibition of the ascending nociceptive transmission and activation of descending pathways. However, the relative importance of the spinal and supraspinal sites in the analgesic action of systemic opioids remains uncertain. It has been shown that systemic morphine can inhibit dorsal horn neurons independent of the descending system. ⋯ Intrathecal CTAP similarly abolished the effect of subcutaneous fentanyl on thermal nociception of the hindpaw but not the forepaw. Therefore, this study provides new information that when spinal mu opioid receptors are blocked, subsequent systemic administration of mu opioids fails to produce an analgesic effect. This finding highlights the important role of mu opioid receptors in the spinal cord in the antinociceptive action of opioids.